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JAK inhibitor therapy promising for refractory dermatomyositis
ORLANDO – The according to Ruth Ann Vleugels, MD, director of the autoimmune skin diseases program at Brigham and Women’s Hospital, Boston.
“We will have patients who essentially fail all of our typical therapies and are still coming to us for help. This is a huge challenge,” said Dr. Vleugels, who, several years ago, started to use tofacitinib to treat these patients. “Similar to my colleagues who use tofacitinib to treat alopecia areata, we often have to push” beyond the dose used to treat rheumatoid arthritis, to 10 mg twice a day, she said at the International Conference on Cutaneous Lupus Erythematosus. Tofacitinib helps counter the overexpression of interferon in DM.
Getting insurance coverage for this off-label indication can be tough, however, but Dr. Vleugels said she’s had success when she tells insurers that tofacitinib will likely reduce the need for IVIg.
It’s safe to keep patients on methotrexate if there are concerns about muscle involvement while their skin is brought under control with tofacitinib. In terms of side effects, “we see increased shingles,” so recommending the shingles vaccine for these patients is a good idea, she added.
It’s also important to counsel DM patients that they are at particular risk for skin reactions with antimalarials, which can be serious, so that, “if there is a drug reaction that develops, it’s noticed right away” and the drug can be stopped, she said. “If you have a patient who has very severe disease, I might skip over an antimalarial altogether,” she commented.
Methotrexate is the next option, especially if there are work ups for cancer or the patients have cancer, but Dr. Femia, director of inpatient dermatology at NYU, said she leans towards mycophenolate if there’s concern about lung involvement.
The next step, if necessary, is IVIg, which she said is “particularly helpful” for recalcitrant skin disease and can help some patients discontinue other immunosuppressives. To counter headache, a common side effect, she will space dosing out over 3 days, instead of the usual 2, and have a bag of saline administered before and after the infusion to keep patients hydrated; this counters the headache-inducing viscosity of IVIg.
Patients often see a result after the first infusion, but if there’s no benefit by the third cycle, “it’s probably time to move on,” she said. “If you have a refractory muscle disease patient and skin isn’t the main issue, rituximab is reasonable to try,” she added, noting that the benefit of tumor necrosis factor blockers, “at best, is very mixed in the DM population. They are very low down in the treatment algorithm.”
Dr. Vleugels and Dr. Femia are both Pfizer investigators.
ORLANDO – The according to Ruth Ann Vleugels, MD, director of the autoimmune skin diseases program at Brigham and Women’s Hospital, Boston.
“We will have patients who essentially fail all of our typical therapies and are still coming to us for help. This is a huge challenge,” said Dr. Vleugels, who, several years ago, started to use tofacitinib to treat these patients. “Similar to my colleagues who use tofacitinib to treat alopecia areata, we often have to push” beyond the dose used to treat rheumatoid arthritis, to 10 mg twice a day, she said at the International Conference on Cutaneous Lupus Erythematosus. Tofacitinib helps counter the overexpression of interferon in DM.
Getting insurance coverage for this off-label indication can be tough, however, but Dr. Vleugels said she’s had success when she tells insurers that tofacitinib will likely reduce the need for IVIg.
It’s safe to keep patients on methotrexate if there are concerns about muscle involvement while their skin is brought under control with tofacitinib. In terms of side effects, “we see increased shingles,” so recommending the shingles vaccine for these patients is a good idea, she added.
It’s also important to counsel DM patients that they are at particular risk for skin reactions with antimalarials, which can be serious, so that, “if there is a drug reaction that develops, it’s noticed right away” and the drug can be stopped, she said. “If you have a patient who has very severe disease, I might skip over an antimalarial altogether,” she commented.
Methotrexate is the next option, especially if there are work ups for cancer or the patients have cancer, but Dr. Femia, director of inpatient dermatology at NYU, said she leans towards mycophenolate if there’s concern about lung involvement.
The next step, if necessary, is IVIg, which she said is “particularly helpful” for recalcitrant skin disease and can help some patients discontinue other immunosuppressives. To counter headache, a common side effect, she will space dosing out over 3 days, instead of the usual 2, and have a bag of saline administered before and after the infusion to keep patients hydrated; this counters the headache-inducing viscosity of IVIg.
Patients often see a result after the first infusion, but if there’s no benefit by the third cycle, “it’s probably time to move on,” she said. “If you have a refractory muscle disease patient and skin isn’t the main issue, rituximab is reasonable to try,” she added, noting that the benefit of tumor necrosis factor blockers, “at best, is very mixed in the DM population. They are very low down in the treatment algorithm.”
Dr. Vleugels and Dr. Femia are both Pfizer investigators.
ORLANDO – The according to Ruth Ann Vleugels, MD, director of the autoimmune skin diseases program at Brigham and Women’s Hospital, Boston.
“We will have patients who essentially fail all of our typical therapies and are still coming to us for help. This is a huge challenge,” said Dr. Vleugels, who, several years ago, started to use tofacitinib to treat these patients. “Similar to my colleagues who use tofacitinib to treat alopecia areata, we often have to push” beyond the dose used to treat rheumatoid arthritis, to 10 mg twice a day, she said at the International Conference on Cutaneous Lupus Erythematosus. Tofacitinib helps counter the overexpression of interferon in DM.
Getting insurance coverage for this off-label indication can be tough, however, but Dr. Vleugels said she’s had success when she tells insurers that tofacitinib will likely reduce the need for IVIg.
It’s safe to keep patients on methotrexate if there are concerns about muscle involvement while their skin is brought under control with tofacitinib. In terms of side effects, “we see increased shingles,” so recommending the shingles vaccine for these patients is a good idea, she added.
It’s also important to counsel DM patients that they are at particular risk for skin reactions with antimalarials, which can be serious, so that, “if there is a drug reaction that develops, it’s noticed right away” and the drug can be stopped, she said. “If you have a patient who has very severe disease, I might skip over an antimalarial altogether,” she commented.
Methotrexate is the next option, especially if there are work ups for cancer or the patients have cancer, but Dr. Femia, director of inpatient dermatology at NYU, said she leans towards mycophenolate if there’s concern about lung involvement.
The next step, if necessary, is IVIg, which she said is “particularly helpful” for recalcitrant skin disease and can help some patients discontinue other immunosuppressives. To counter headache, a common side effect, she will space dosing out over 3 days, instead of the usual 2, and have a bag of saline administered before and after the infusion to keep patients hydrated; this counters the headache-inducing viscosity of IVIg.
Patients often see a result after the first infusion, but if there’s no benefit by the third cycle, “it’s probably time to move on,” she said. “If you have a refractory muscle disease patient and skin isn’t the main issue, rituximab is reasonable to try,” she added, noting that the benefit of tumor necrosis factor blockers, “at best, is very mixed in the DM population. They are very low down in the treatment algorithm.”
Dr. Vleugels and Dr. Femia are both Pfizer investigators.
EXPERT ANALYSIS FROM ICCLE 2018
SLE classification criteria perform well in validation study
AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.
This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).
The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.
One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).
Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).
The final, simplified draft SLE classification criteria include 22 items in addition to the presence of ANA. A cut-off score of 10 or more is required for a classification of SLE. For example, a patient with an ANA of 1:80 or higher plus class III/IV nephritis (scoring 10) would be classified as having SLE. A patient with class II/V nephritis (scoring 8) would need another factor to be classified as having lupus, such as the presence of arthritis (scoring 6).
“Performance characteristics find sensitivity similar to the SLICC criteria while maintaining the specificity of the ACR 1997 criteria,” Dr. Aringer said, adding that these criteria will now be formally submitted to and reviewed by EULAR and ACR.
The sensitivity and specificity of the new criteria were 98% and 96% in the derivation cohort and 96% and 93% in the validation cohort.
“I was really very pleased and very happy to see that the revised or the new ACR/EULAR classification criteria had sensitivity and specificity of above 90%,” Thomas Dörner, MD, PhD, said in an interview at the congress. Dr. Dörner was a codeveloper of these criteria.
Over the past 10-15 years there have been several therapies that have failed to live up to their early promise as a potential treatment for lupus, said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. He noted that the failed treatment trials had led investigators to try to determine ways in which lupus might be best treated, such as by a “treat-to-target” approach to attain remission and low-disease activity. It also led to the reevaluation of how lupus is classified to see if that might be affecting the population of patients recruited into clinical trials.
“We had the feeling, and this is now confirmed by the new classification criteria, that a number of patients studied in earlier trials may have not fulfilled what we think is the classical lupus profile, so-called lupus or SLE mimickers,” Dr. Dörner said. This could have affected the chances of a treatment approach being successful versus placebo.
The new classification criteria are similar to those in other rheumatic diseases in that they give different weight to the effects on different organ systems, Dr. Dörner said. The stipulation that there must be a positive ANA test is also an important step, “really to make sure that we are looking at an autoimmune disease and nothing else,” he observed.
For patients who do not have a positive ANA test, they can of course still be treated, Dr. Dörner reassured, but for the classification criteria and entering patients into clinical trials, it’s really important to have strict classification criteria so that the results may be compared.
Dr. Aringer and Dr. Dörner had no relevant disclosures besides their involvement in developing the new classification criteria.
SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.
AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.
This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).
The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.
One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).
Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).
The final, simplified draft SLE classification criteria include 22 items in addition to the presence of ANA. A cut-off score of 10 or more is required for a classification of SLE. For example, a patient with an ANA of 1:80 or higher plus class III/IV nephritis (scoring 10) would be classified as having SLE. A patient with class II/V nephritis (scoring 8) would need another factor to be classified as having lupus, such as the presence of arthritis (scoring 6).
“Performance characteristics find sensitivity similar to the SLICC criteria while maintaining the specificity of the ACR 1997 criteria,” Dr. Aringer said, adding that these criteria will now be formally submitted to and reviewed by EULAR and ACR.
The sensitivity and specificity of the new criteria were 98% and 96% in the derivation cohort and 96% and 93% in the validation cohort.
“I was really very pleased and very happy to see that the revised or the new ACR/EULAR classification criteria had sensitivity and specificity of above 90%,” Thomas Dörner, MD, PhD, said in an interview at the congress. Dr. Dörner was a codeveloper of these criteria.
Over the past 10-15 years there have been several therapies that have failed to live up to their early promise as a potential treatment for lupus, said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. He noted that the failed treatment trials had led investigators to try to determine ways in which lupus might be best treated, such as by a “treat-to-target” approach to attain remission and low-disease activity. It also led to the reevaluation of how lupus is classified to see if that might be affecting the population of patients recruited into clinical trials.
“We had the feeling, and this is now confirmed by the new classification criteria, that a number of patients studied in earlier trials may have not fulfilled what we think is the classical lupus profile, so-called lupus or SLE mimickers,” Dr. Dörner said. This could have affected the chances of a treatment approach being successful versus placebo.
The new classification criteria are similar to those in other rheumatic diseases in that they give different weight to the effects on different organ systems, Dr. Dörner said. The stipulation that there must be a positive ANA test is also an important step, “really to make sure that we are looking at an autoimmune disease and nothing else,” he observed.
For patients who do not have a positive ANA test, they can of course still be treated, Dr. Dörner reassured, but for the classification criteria and entering patients into clinical trials, it’s really important to have strict classification criteria so that the results may be compared.
Dr. Aringer and Dr. Dörner had no relevant disclosures besides their involvement in developing the new classification criteria.
SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.
AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.
This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).
The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.
One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).
Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).
The final, simplified draft SLE classification criteria include 22 items in addition to the presence of ANA. A cut-off score of 10 or more is required for a classification of SLE. For example, a patient with an ANA of 1:80 or higher plus class III/IV nephritis (scoring 10) would be classified as having SLE. A patient with class II/V nephritis (scoring 8) would need another factor to be classified as having lupus, such as the presence of arthritis (scoring 6).
“Performance characteristics find sensitivity similar to the SLICC criteria while maintaining the specificity of the ACR 1997 criteria,” Dr. Aringer said, adding that these criteria will now be formally submitted to and reviewed by EULAR and ACR.
The sensitivity and specificity of the new criteria were 98% and 96% in the derivation cohort and 96% and 93% in the validation cohort.
“I was really very pleased and very happy to see that the revised or the new ACR/EULAR classification criteria had sensitivity and specificity of above 90%,” Thomas Dörner, MD, PhD, said in an interview at the congress. Dr. Dörner was a codeveloper of these criteria.
Over the past 10-15 years there have been several therapies that have failed to live up to their early promise as a potential treatment for lupus, said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. He noted that the failed treatment trials had led investigators to try to determine ways in which lupus might be best treated, such as by a “treat-to-target” approach to attain remission and low-disease activity. It also led to the reevaluation of how lupus is classified to see if that might be affecting the population of patients recruited into clinical trials.
“We had the feeling, and this is now confirmed by the new classification criteria, that a number of patients studied in earlier trials may have not fulfilled what we think is the classical lupus profile, so-called lupus or SLE mimickers,” Dr. Dörner said. This could have affected the chances of a treatment approach being successful versus placebo.
The new classification criteria are similar to those in other rheumatic diseases in that they give different weight to the effects on different organ systems, Dr. Dörner said. The stipulation that there must be a positive ANA test is also an important step, “really to make sure that we are looking at an autoimmune disease and nothing else,” he observed.
For patients who do not have a positive ANA test, they can of course still be treated, Dr. Dörner reassured, but for the classification criteria and entering patients into clinical trials, it’s really important to have strict classification criteria so that the results may be compared.
Dr. Aringer and Dr. Dörner had no relevant disclosures besides their involvement in developing the new classification criteria.
SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: New classification criteria for systemic lupus erythematosus (SLE) achieve both high sensitivity and specificity.
Major finding: The sensitivity and specificity of the new criteria were 98% and 96% in the derivation cohort and 96% and 93% in the validation cohort.
Study details: An international cohort of 1,160 SLE patients and 1,058 non-SLE patients in whom the new criteria were tested and validated.
Disclosures: Dr. Aringer and Dr. Dörner had no relevant disclosures besides their involvement in developing the new classification criteria.
Source: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.
Cost of medical care for older adults with epilepsy steadily grows
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
FROM EPILEPSIA
Pediatric asthma patients should be considered priority for flu vaccine
Children with asthma who present to emergency departments for treatment are significantly more likely to test positive for one or more respiratory pathogens, reported Dr. Joanna Merckx of the Montreal Children’s Hospital at the McGill University Health Centre, and her associates.
Nearly two-thirds of patients tested positive for one or more respiratory viruses in a study conducted by Dr. Merckx and her associates. “Given the documented safety of influenza immunization in children with asthma and its expected protective effect,” such cases should be among those prioritized to receive influenza immunization.
In reviewing the findings of the study, Dr. Merckx and her colleagues sought to determine whether closely evaluating the effects of specific respiratory pathogens could be useful in further developing appropriate preventive treatments for children with asthma; improving efforts to diagnose pathogens at the time of ED treatment; and identifying patients at higher risk of treatment failure who could be candidates for more intensive treatment protocols.
Children aged 1-17 years presenting to one of five EDs in the Pediatric Emergency Research Canada network during 2011-2013 with moderate or severe asthma flares were considered for the study. All eligible DOORWAY study participants with a valid respiratory specimen were included in the study and received a standardized dose of oral and bronchodilator treatment with salbutamol; those with severe exacerbations also received ipratropium bromide (Atrovent).
Within 1 hour of study inclusion, patients were tested by way of nasopharyngeal aspirate or swab. Patients identified with coinfection presented with two or more pathogens. Failure of ED management was defined as patients admitted to the hospital for asthma; ED treatment lasting 8 or more hours after corticosteroid treatment; or returns to the ED within 72 hours after discharge that led to hospital admission or prolonged ED stay.
Of 1,012 children enrolled in the study, 958 were assessed for worsening of asthma symptoms. Of the 958 respiratory specimens tested, 62% tested positive for one or more pathogens, 8.5% were found to have coinfection, of which respiratory syncytial virus (RSV) and coronavirus were the most frequent copathogens. Rhinovirus was the most prevalent pathogen, occurring in 29%, and of these, rhinovirus C was the most frequent species (18.2%), followed by RSV (17.9%); only two patients tested positive for Mycoplasma pneumoniae.
Children with a laboratory-confirmed pathogen were younger, had higher tobacco exposure, and were slightly more likely to present with fever (29% vs. 24%), compared with children without a laboratory-confirmed pathogen. Children with rhinovirus were less often febrile (16% vs 41%) and less frequently diagnosed with pneumonia (5% vs. 16%.) than those without a rhinovirus infection The proportion of children presenting with a severe exacerbation of asthma was 33%.
Overall, 17% of patients experienced treatment failure. Those with current respiratory infection were at increased risk of treatment failure, for a risk difference of 8% (95% confidence interval, 3.3%-13.1%). RSV, influenza, and parainfluenza virus (PIV) were associated with 21%, 38%, and 47% higher risks of treatment failure, respectively, noted Dr. Merckx and her associates. These resulted in absolute risks of 9%, 25%, and 34%, respectively, the authors reported in Pediatrics.
Coronavirus, adenovirus, enterovirus D68, and the presence of a coinfection, however, were not found to increase the risk of treatment failure, they noted.
Although rhinovirus may play a role in triggering reactions that require medical attention, such cases still appear to respond favorably to treatment, they said.
A separate study cited by Dr. Merckx and her associates observed the same outcome for rhinovirus patients but more patients diagnosed with nonrhinovirus pathogens, especially human metapneumovirus (hMPV) and PIV, had moderate, rather than severe, symptoms and were much more likely to experience higher treatment failure, particularly those infected with RSV, influenza, and PIV.
“It appears reasonable to pursue strategies to improve immunization coverage for influenza and invest in efforts for the development of vaccines for RSV and rhinovirus,” they said.
In cases in which respiratory pathogens were present (especially nonrhinovirus pathogens), greater treatment failure occurred, despite use of inhaler and corticosteroids. The researchers noted that severity of condition at time of treatment and patient response to treatment should be considered as two separate, distinct dimensions of viral infection impact in children with acute asthma. “The high prevalence of rhinovirus C in children presenting with asthma exacerbation, its presumed association with asthma-related hospitalization, and its peak in the fall,” also should be considered as a leading cause for more potential severe disease.
Dr. Merckx and her associates did point to several possibly significant implications with their findings. Intensifying treatment using inhaled anticholinergics or magnesium sulfate could block the vagally mediated reflex bronchoconstriction typically seen in cases of asthma exacerbation worsened by viral infection. Although these therapies currently only are used only in severe reactions, it may be useful to examine their efficacy in any cases triggered by RSV, influenza, and PIV because these have been associated with a poor treatment response.
While it still is necessary to clarify its mechanism of action, azithromycin’s demonstrated benefit in preschoolers with severe reactions suggests it could be a possible alternative pathogen–nonspecific therapy to address antineutrophilic inflammation, they said.
Any treatment intensification would first require clear identification of responsible pathogens using on-site diagnostic measures in the ED. Until such testing is possible, preventive measures need to be prioritized, they advised.
Dr. Merckx had no relevant disclosures; two of her associates reported receiving grants, salary rewards, and/or unrestricted donations from various pharmaceutical companies or foundations.
SOURCE: Merckx J et al. Pediatrics. 2018 Jun;142(1):e20174105.
Children with asthma who present to emergency departments for treatment are significantly more likely to test positive for one or more respiratory pathogens, reported Dr. Joanna Merckx of the Montreal Children’s Hospital at the McGill University Health Centre, and her associates.
Nearly two-thirds of patients tested positive for one or more respiratory viruses in a study conducted by Dr. Merckx and her associates. “Given the documented safety of influenza immunization in children with asthma and its expected protective effect,” such cases should be among those prioritized to receive influenza immunization.
In reviewing the findings of the study, Dr. Merckx and her colleagues sought to determine whether closely evaluating the effects of specific respiratory pathogens could be useful in further developing appropriate preventive treatments for children with asthma; improving efforts to diagnose pathogens at the time of ED treatment; and identifying patients at higher risk of treatment failure who could be candidates for more intensive treatment protocols.
Children aged 1-17 years presenting to one of five EDs in the Pediatric Emergency Research Canada network during 2011-2013 with moderate or severe asthma flares were considered for the study. All eligible DOORWAY study participants with a valid respiratory specimen were included in the study and received a standardized dose of oral and bronchodilator treatment with salbutamol; those with severe exacerbations also received ipratropium bromide (Atrovent).
Within 1 hour of study inclusion, patients were tested by way of nasopharyngeal aspirate or swab. Patients identified with coinfection presented with two or more pathogens. Failure of ED management was defined as patients admitted to the hospital for asthma; ED treatment lasting 8 or more hours after corticosteroid treatment; or returns to the ED within 72 hours after discharge that led to hospital admission or prolonged ED stay.
Of 1,012 children enrolled in the study, 958 were assessed for worsening of asthma symptoms. Of the 958 respiratory specimens tested, 62% tested positive for one or more pathogens, 8.5% were found to have coinfection, of which respiratory syncytial virus (RSV) and coronavirus were the most frequent copathogens. Rhinovirus was the most prevalent pathogen, occurring in 29%, and of these, rhinovirus C was the most frequent species (18.2%), followed by RSV (17.9%); only two patients tested positive for Mycoplasma pneumoniae.
Children with a laboratory-confirmed pathogen were younger, had higher tobacco exposure, and were slightly more likely to present with fever (29% vs. 24%), compared with children without a laboratory-confirmed pathogen. Children with rhinovirus were less often febrile (16% vs 41%) and less frequently diagnosed with pneumonia (5% vs. 16%.) than those without a rhinovirus infection The proportion of children presenting with a severe exacerbation of asthma was 33%.
Overall, 17% of patients experienced treatment failure. Those with current respiratory infection were at increased risk of treatment failure, for a risk difference of 8% (95% confidence interval, 3.3%-13.1%). RSV, influenza, and parainfluenza virus (PIV) were associated with 21%, 38%, and 47% higher risks of treatment failure, respectively, noted Dr. Merckx and her associates. These resulted in absolute risks of 9%, 25%, and 34%, respectively, the authors reported in Pediatrics.
Coronavirus, adenovirus, enterovirus D68, and the presence of a coinfection, however, were not found to increase the risk of treatment failure, they noted.
Although rhinovirus may play a role in triggering reactions that require medical attention, such cases still appear to respond favorably to treatment, they said.
A separate study cited by Dr. Merckx and her associates observed the same outcome for rhinovirus patients but more patients diagnosed with nonrhinovirus pathogens, especially human metapneumovirus (hMPV) and PIV, had moderate, rather than severe, symptoms and were much more likely to experience higher treatment failure, particularly those infected with RSV, influenza, and PIV.
“It appears reasonable to pursue strategies to improve immunization coverage for influenza and invest in efforts for the development of vaccines for RSV and rhinovirus,” they said.
In cases in which respiratory pathogens were present (especially nonrhinovirus pathogens), greater treatment failure occurred, despite use of inhaler and corticosteroids. The researchers noted that severity of condition at time of treatment and patient response to treatment should be considered as two separate, distinct dimensions of viral infection impact in children with acute asthma. “The high prevalence of rhinovirus C in children presenting with asthma exacerbation, its presumed association with asthma-related hospitalization, and its peak in the fall,” also should be considered as a leading cause for more potential severe disease.
Dr. Merckx and her associates did point to several possibly significant implications with their findings. Intensifying treatment using inhaled anticholinergics or magnesium sulfate could block the vagally mediated reflex bronchoconstriction typically seen in cases of asthma exacerbation worsened by viral infection. Although these therapies currently only are used only in severe reactions, it may be useful to examine their efficacy in any cases triggered by RSV, influenza, and PIV because these have been associated with a poor treatment response.
While it still is necessary to clarify its mechanism of action, azithromycin’s demonstrated benefit in preschoolers with severe reactions suggests it could be a possible alternative pathogen–nonspecific therapy to address antineutrophilic inflammation, they said.
Any treatment intensification would first require clear identification of responsible pathogens using on-site diagnostic measures in the ED. Until such testing is possible, preventive measures need to be prioritized, they advised.
Dr. Merckx had no relevant disclosures; two of her associates reported receiving grants, salary rewards, and/or unrestricted donations from various pharmaceutical companies or foundations.
SOURCE: Merckx J et al. Pediatrics. 2018 Jun;142(1):e20174105.
Children with asthma who present to emergency departments for treatment are significantly more likely to test positive for one or more respiratory pathogens, reported Dr. Joanna Merckx of the Montreal Children’s Hospital at the McGill University Health Centre, and her associates.
Nearly two-thirds of patients tested positive for one or more respiratory viruses in a study conducted by Dr. Merckx and her associates. “Given the documented safety of influenza immunization in children with asthma and its expected protective effect,” such cases should be among those prioritized to receive influenza immunization.
In reviewing the findings of the study, Dr. Merckx and her colleagues sought to determine whether closely evaluating the effects of specific respiratory pathogens could be useful in further developing appropriate preventive treatments for children with asthma; improving efforts to diagnose pathogens at the time of ED treatment; and identifying patients at higher risk of treatment failure who could be candidates for more intensive treatment protocols.
Children aged 1-17 years presenting to one of five EDs in the Pediatric Emergency Research Canada network during 2011-2013 with moderate or severe asthma flares were considered for the study. All eligible DOORWAY study participants with a valid respiratory specimen were included in the study and received a standardized dose of oral and bronchodilator treatment with salbutamol; those with severe exacerbations also received ipratropium bromide (Atrovent).
Within 1 hour of study inclusion, patients were tested by way of nasopharyngeal aspirate or swab. Patients identified with coinfection presented with two or more pathogens. Failure of ED management was defined as patients admitted to the hospital for asthma; ED treatment lasting 8 or more hours after corticosteroid treatment; or returns to the ED within 72 hours after discharge that led to hospital admission or prolonged ED stay.
Of 1,012 children enrolled in the study, 958 were assessed for worsening of asthma symptoms. Of the 958 respiratory specimens tested, 62% tested positive for one or more pathogens, 8.5% were found to have coinfection, of which respiratory syncytial virus (RSV) and coronavirus were the most frequent copathogens. Rhinovirus was the most prevalent pathogen, occurring in 29%, and of these, rhinovirus C was the most frequent species (18.2%), followed by RSV (17.9%); only two patients tested positive for Mycoplasma pneumoniae.
Children with a laboratory-confirmed pathogen were younger, had higher tobacco exposure, and were slightly more likely to present with fever (29% vs. 24%), compared with children without a laboratory-confirmed pathogen. Children with rhinovirus were less often febrile (16% vs 41%) and less frequently diagnosed with pneumonia (5% vs. 16%.) than those without a rhinovirus infection The proportion of children presenting with a severe exacerbation of asthma was 33%.
Overall, 17% of patients experienced treatment failure. Those with current respiratory infection were at increased risk of treatment failure, for a risk difference of 8% (95% confidence interval, 3.3%-13.1%). RSV, influenza, and parainfluenza virus (PIV) were associated with 21%, 38%, and 47% higher risks of treatment failure, respectively, noted Dr. Merckx and her associates. These resulted in absolute risks of 9%, 25%, and 34%, respectively, the authors reported in Pediatrics.
Coronavirus, adenovirus, enterovirus D68, and the presence of a coinfection, however, were not found to increase the risk of treatment failure, they noted.
Although rhinovirus may play a role in triggering reactions that require medical attention, such cases still appear to respond favorably to treatment, they said.
A separate study cited by Dr. Merckx and her associates observed the same outcome for rhinovirus patients but more patients diagnosed with nonrhinovirus pathogens, especially human metapneumovirus (hMPV) and PIV, had moderate, rather than severe, symptoms and were much more likely to experience higher treatment failure, particularly those infected with RSV, influenza, and PIV.
“It appears reasonable to pursue strategies to improve immunization coverage for influenza and invest in efforts for the development of vaccines for RSV and rhinovirus,” they said.
In cases in which respiratory pathogens were present (especially nonrhinovirus pathogens), greater treatment failure occurred, despite use of inhaler and corticosteroids. The researchers noted that severity of condition at time of treatment and patient response to treatment should be considered as two separate, distinct dimensions of viral infection impact in children with acute asthma. “The high prevalence of rhinovirus C in children presenting with asthma exacerbation, its presumed association with asthma-related hospitalization, and its peak in the fall,” also should be considered as a leading cause for more potential severe disease.
Dr. Merckx and her associates did point to several possibly significant implications with their findings. Intensifying treatment using inhaled anticholinergics or magnesium sulfate could block the vagally mediated reflex bronchoconstriction typically seen in cases of asthma exacerbation worsened by viral infection. Although these therapies currently only are used only in severe reactions, it may be useful to examine their efficacy in any cases triggered by RSV, influenza, and PIV because these have been associated with a poor treatment response.
While it still is necessary to clarify its mechanism of action, azithromycin’s demonstrated benefit in preschoolers with severe reactions suggests it could be a possible alternative pathogen–nonspecific therapy to address antineutrophilic inflammation, they said.
Any treatment intensification would first require clear identification of responsible pathogens using on-site diagnostic measures in the ED. Until such testing is possible, preventive measures need to be prioritized, they advised.
Dr. Merckx had no relevant disclosures; two of her associates reported receiving grants, salary rewards, and/or unrestricted donations from various pharmaceutical companies or foundations.
SOURCE: Merckx J et al. Pediatrics. 2018 Jun;142(1):e20174105.
FROM PEDIATRICS
Key clinical point: Nearly two-thirds of emergency asthma cases test positive for multiple pathogens.
Major finding: Risk of treatment failure is higher with respiratory syncytial virus, influenza, and parainfluenza virus.
Study details: Ancillary multicenter, prospective, ethics-approved cohort study of 958 children with asthma.
Disclosures: Dr. Merckx had no relevant disclosures; two of her associates reported receiving grants, salary rewards, and/or unrestricted donations from various pharmaceutical companies or foundations.
Source: Merckx J et al. Pediatrics. 2018;142(1):e20174105.
Q&A: Clinical implications of clonal hematopoiesis
There is growing literature around clonal hematopoiesis (CH) but many questions persist about its clinical significance. On June 14, Hematology News hosted a Twitter question-and-answer session with Aaron Viny, MD, who is on the staff of the leukemia service at Memorial Sloan Kettering Cancer Center in New York and is a member of the Hematology News editorial advisory board, to answer questions about CH and interpret the latest research. The following is an edited version of the Q&A session.
Question: Can you get us started by explaining the difference between clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance?
Question: So are there differences in CH depending on the gene mutated?
Dr. Viny: Hard to say. The most common mutations found in CH are DNMT3A, TET2, PPM1D, and ASXL1, as shown in the Cell Stem Cell paper by Catherine C. Coombs, MD, and Ross Levine, MD (2017 Sep 7;21[3]:374-82.e4). So in the setting of patients with acute myeloid leukemia, there are data from several groups showing that persistence of DNMT3A, TET2, and ASXL1 have less recurrence risk, compared with the field. This, of course, does not apply to CH in the absence of a hematologic disorder.
Question: Are you aware of any screening programs for clonal hematopoiesis?
Dr. Viny: Currently at Memorial Sloan Kettering, patients who undergo MSK-IMPACT testing of their solid tumor have a germ line control from blood that is also sequenced. These samples are screened for CH mutations. In fact, there are two recent papers showing one key issue with tumor sequencing and CH: A blood sample is necessary to resolve the compartment of the CH mutation (that is, not in the solid tumor). The papers are JAMA Oncol. 2018 Jun 5. doi: 10.1001/jamaoncol.2018.2297 and Clin Cancer Res. 2018 Jun 4. doi: 10.1158/1078-0432.CCR-18-1201.
Question: Will patients with CH in screened samples be notified of the results?
Dr. Viny: Yes. The patients are being referred to the Memorial Sloan Kettering clonal hematopoiesis clinic run by Dr. Levine and Kelly Bolton, MD.
Question: Once you screen and detect CH, how should these patients be followed?
Dr. Viny: First, what are the risks these patients face? Extensive work by Siddhartha Jaiswal, MD, PhD, shows that there is an increased risk of cardiovascular disease and an increased risk for leukemia. So with regards to the latter, following with serial complete blood counts seems sufficient, with a bone marrow biopsy at the detection of any cytopenias. With regard to cardiovascular risk, I consider CH akin to an unmodifiable cardiac risk factor. Patients should be counseled to exercise, and depending on any other cardiac risk factors, interventions such as blood pressure control, lipid control, and daily aspirin use should be addressed accordingly.
Question: Is this BRCA1 all over again?
Dr. Viny: Perhaps. With BRCA1, we now have a few decades of follow-up to better understand the risks and even intervene with preventive interventions. Clonal hematopoiesis needs the follow-up and research to support clinical action.
Question: Could you please refer your readers to your favorite review on clonal hematopoiesis?
Dr. Viny: An outstanding review of the mechanisms and molecular consequences of clonal hematopoiesis is in Cell Stem Cell (2018 Feb 1;22[2]:157-70).
Question: Are there any effects of previous radiation on the development of CH?
Dr. Viny: Let’s start by saying that CH in the absence of prior cancer is probably a different entity. Radiation, tobacco use, and increased age all increase the risk for detection of a CH somatic mutation.
Question: What are the clinical implications of CH?
Dr. Viny: While I think it is still too soon to say if these are the only clinical implications, both increased risk of hematologic malignancy and increased risk of cardiovascular disease are the best studied and described to date. Here’s an excellent article on the cardiovascular risk: N Engl J Med. 2017 Jul 13;377(2):111-21. Of interest, it seems that the increased risk, while being relatively low, does not plateau over time.
Question: What do you think about TET2 mutations being among the most frequent mutations in CH, but IDH being relatively rare?
Dr. Viny: Great question. Both are affecting demethylation and epigenetic instability. While I don’t think the answer is known, perhaps the IDH mutations have a more dominant effect on hematopoietic output. The majority of the CH data uses blood; maybe the marrow tells a different story.
Question: Can we cure clonal hematopoiesis with vitamin C?
Dr. Viny: You clearly know the recent work by Iannis Aifantis, PhD, showing the effects of vitamin C on TET enzyme activity, published here: Cell. 2017 Sep 7;170(6):1079-95. For CH patients with TET2 mutations, a high-dose vitamin C regimen sounds very exciting. There is also complementary work by Sean Morrison, PhD, published in Nature (2017 Sep 28;549[7673]:476-81).
Question: Is there a limit to the sequencing depth and variant allele fraction needed to identify clonal hematopoiesis? At what point is CH not CH?
Dr. Viny: So this is as much a technical question as it is a biological question. As of now we can reliably detect variant allele fraction in CH to 0.1%, at best. What is detectable and what is clinically relevant are questions that still need to be answered.
Question: There seems to be a lot of good research going on in CH. What are the big knowledge gaps that future studies should be targeting?
Dr. Viny: First, what are the functional and molecular consequences of the varying alleles in CH? Second, are there other clinical risks to CH beyond leukemia and cardiovascular disease? And third, does inflammation cause CH or does CH cause inflammation?
Dr. Viny is with the Memorial Sloan Kettering Cancer Center, New York, where he is a clinical instructor; is on the staff of the leukemia service; and is a clinical researcher in the Ross Levine Lab. Connect with him on Twitter at @TheDoctorIsVin.
There is growing literature around clonal hematopoiesis (CH) but many questions persist about its clinical significance. On June 14, Hematology News hosted a Twitter question-and-answer session with Aaron Viny, MD, who is on the staff of the leukemia service at Memorial Sloan Kettering Cancer Center in New York and is a member of the Hematology News editorial advisory board, to answer questions about CH and interpret the latest research. The following is an edited version of the Q&A session.
Question: Can you get us started by explaining the difference between clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance?
Question: So are there differences in CH depending on the gene mutated?
Dr. Viny: Hard to say. The most common mutations found in CH are DNMT3A, TET2, PPM1D, and ASXL1, as shown in the Cell Stem Cell paper by Catherine C. Coombs, MD, and Ross Levine, MD (2017 Sep 7;21[3]:374-82.e4). So in the setting of patients with acute myeloid leukemia, there are data from several groups showing that persistence of DNMT3A, TET2, and ASXL1 have less recurrence risk, compared with the field. This, of course, does not apply to CH in the absence of a hematologic disorder.
Question: Are you aware of any screening programs for clonal hematopoiesis?
Dr. Viny: Currently at Memorial Sloan Kettering, patients who undergo MSK-IMPACT testing of their solid tumor have a germ line control from blood that is also sequenced. These samples are screened for CH mutations. In fact, there are two recent papers showing one key issue with tumor sequencing and CH: A blood sample is necessary to resolve the compartment of the CH mutation (that is, not in the solid tumor). The papers are JAMA Oncol. 2018 Jun 5. doi: 10.1001/jamaoncol.2018.2297 and Clin Cancer Res. 2018 Jun 4. doi: 10.1158/1078-0432.CCR-18-1201.
Question: Will patients with CH in screened samples be notified of the results?
Dr. Viny: Yes. The patients are being referred to the Memorial Sloan Kettering clonal hematopoiesis clinic run by Dr. Levine and Kelly Bolton, MD.
Question: Once you screen and detect CH, how should these patients be followed?
Dr. Viny: First, what are the risks these patients face? Extensive work by Siddhartha Jaiswal, MD, PhD, shows that there is an increased risk of cardiovascular disease and an increased risk for leukemia. So with regards to the latter, following with serial complete blood counts seems sufficient, with a bone marrow biopsy at the detection of any cytopenias. With regard to cardiovascular risk, I consider CH akin to an unmodifiable cardiac risk factor. Patients should be counseled to exercise, and depending on any other cardiac risk factors, interventions such as blood pressure control, lipid control, and daily aspirin use should be addressed accordingly.
Question: Is this BRCA1 all over again?
Dr. Viny: Perhaps. With BRCA1, we now have a few decades of follow-up to better understand the risks and even intervene with preventive interventions. Clonal hematopoiesis needs the follow-up and research to support clinical action.
Question: Could you please refer your readers to your favorite review on clonal hematopoiesis?
Dr. Viny: An outstanding review of the mechanisms and molecular consequences of clonal hematopoiesis is in Cell Stem Cell (2018 Feb 1;22[2]:157-70).
Question: Are there any effects of previous radiation on the development of CH?
Dr. Viny: Let’s start by saying that CH in the absence of prior cancer is probably a different entity. Radiation, tobacco use, and increased age all increase the risk for detection of a CH somatic mutation.
Question: What are the clinical implications of CH?
Dr. Viny: While I think it is still too soon to say if these are the only clinical implications, both increased risk of hematologic malignancy and increased risk of cardiovascular disease are the best studied and described to date. Here’s an excellent article on the cardiovascular risk: N Engl J Med. 2017 Jul 13;377(2):111-21. Of interest, it seems that the increased risk, while being relatively low, does not plateau over time.
Question: What do you think about TET2 mutations being among the most frequent mutations in CH, but IDH being relatively rare?
Dr. Viny: Great question. Both are affecting demethylation and epigenetic instability. While I don’t think the answer is known, perhaps the IDH mutations have a more dominant effect on hematopoietic output. The majority of the CH data uses blood; maybe the marrow tells a different story.
Question: Can we cure clonal hematopoiesis with vitamin C?
Dr. Viny: You clearly know the recent work by Iannis Aifantis, PhD, showing the effects of vitamin C on TET enzyme activity, published here: Cell. 2017 Sep 7;170(6):1079-95. For CH patients with TET2 mutations, a high-dose vitamin C regimen sounds very exciting. There is also complementary work by Sean Morrison, PhD, published in Nature (2017 Sep 28;549[7673]:476-81).
Question: Is there a limit to the sequencing depth and variant allele fraction needed to identify clonal hematopoiesis? At what point is CH not CH?
Dr. Viny: So this is as much a technical question as it is a biological question. As of now we can reliably detect variant allele fraction in CH to 0.1%, at best. What is detectable and what is clinically relevant are questions that still need to be answered.
Question: There seems to be a lot of good research going on in CH. What are the big knowledge gaps that future studies should be targeting?
Dr. Viny: First, what are the functional and molecular consequences of the varying alleles in CH? Second, are there other clinical risks to CH beyond leukemia and cardiovascular disease? And third, does inflammation cause CH or does CH cause inflammation?
Dr. Viny is with the Memorial Sloan Kettering Cancer Center, New York, where he is a clinical instructor; is on the staff of the leukemia service; and is a clinical researcher in the Ross Levine Lab. Connect with him on Twitter at @TheDoctorIsVin.
There is growing literature around clonal hematopoiesis (CH) but many questions persist about its clinical significance. On June 14, Hematology News hosted a Twitter question-and-answer session with Aaron Viny, MD, who is on the staff of the leukemia service at Memorial Sloan Kettering Cancer Center in New York and is a member of the Hematology News editorial advisory board, to answer questions about CH and interpret the latest research. The following is an edited version of the Q&A session.
Question: Can you get us started by explaining the difference between clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance?
Question: So are there differences in CH depending on the gene mutated?
Dr. Viny: Hard to say. The most common mutations found in CH are DNMT3A, TET2, PPM1D, and ASXL1, as shown in the Cell Stem Cell paper by Catherine C. Coombs, MD, and Ross Levine, MD (2017 Sep 7;21[3]:374-82.e4). So in the setting of patients with acute myeloid leukemia, there are data from several groups showing that persistence of DNMT3A, TET2, and ASXL1 have less recurrence risk, compared with the field. This, of course, does not apply to CH in the absence of a hematologic disorder.
Question: Are you aware of any screening programs for clonal hematopoiesis?
Dr. Viny: Currently at Memorial Sloan Kettering, patients who undergo MSK-IMPACT testing of their solid tumor have a germ line control from blood that is also sequenced. These samples are screened for CH mutations. In fact, there are two recent papers showing one key issue with tumor sequencing and CH: A blood sample is necessary to resolve the compartment of the CH mutation (that is, not in the solid tumor). The papers are JAMA Oncol. 2018 Jun 5. doi: 10.1001/jamaoncol.2018.2297 and Clin Cancer Res. 2018 Jun 4. doi: 10.1158/1078-0432.CCR-18-1201.
Question: Will patients with CH in screened samples be notified of the results?
Dr. Viny: Yes. The patients are being referred to the Memorial Sloan Kettering clonal hematopoiesis clinic run by Dr. Levine and Kelly Bolton, MD.
Question: Once you screen and detect CH, how should these patients be followed?
Dr. Viny: First, what are the risks these patients face? Extensive work by Siddhartha Jaiswal, MD, PhD, shows that there is an increased risk of cardiovascular disease and an increased risk for leukemia. So with regards to the latter, following with serial complete blood counts seems sufficient, with a bone marrow biopsy at the detection of any cytopenias. With regard to cardiovascular risk, I consider CH akin to an unmodifiable cardiac risk factor. Patients should be counseled to exercise, and depending on any other cardiac risk factors, interventions such as blood pressure control, lipid control, and daily aspirin use should be addressed accordingly.
Question: Is this BRCA1 all over again?
Dr. Viny: Perhaps. With BRCA1, we now have a few decades of follow-up to better understand the risks and even intervene with preventive interventions. Clonal hematopoiesis needs the follow-up and research to support clinical action.
Question: Could you please refer your readers to your favorite review on clonal hematopoiesis?
Dr. Viny: An outstanding review of the mechanisms and molecular consequences of clonal hematopoiesis is in Cell Stem Cell (2018 Feb 1;22[2]:157-70).
Question: Are there any effects of previous radiation on the development of CH?
Dr. Viny: Let’s start by saying that CH in the absence of prior cancer is probably a different entity. Radiation, tobacco use, and increased age all increase the risk for detection of a CH somatic mutation.
Question: What are the clinical implications of CH?
Dr. Viny: While I think it is still too soon to say if these are the only clinical implications, both increased risk of hematologic malignancy and increased risk of cardiovascular disease are the best studied and described to date. Here’s an excellent article on the cardiovascular risk: N Engl J Med. 2017 Jul 13;377(2):111-21. Of interest, it seems that the increased risk, while being relatively low, does not plateau over time.
Question: What do you think about TET2 mutations being among the most frequent mutations in CH, but IDH being relatively rare?
Dr. Viny: Great question. Both are affecting demethylation and epigenetic instability. While I don’t think the answer is known, perhaps the IDH mutations have a more dominant effect on hematopoietic output. The majority of the CH data uses blood; maybe the marrow tells a different story.
Question: Can we cure clonal hematopoiesis with vitamin C?
Dr. Viny: You clearly know the recent work by Iannis Aifantis, PhD, showing the effects of vitamin C on TET enzyme activity, published here: Cell. 2017 Sep 7;170(6):1079-95. For CH patients with TET2 mutations, a high-dose vitamin C regimen sounds very exciting. There is also complementary work by Sean Morrison, PhD, published in Nature (2017 Sep 28;549[7673]:476-81).
Question: Is there a limit to the sequencing depth and variant allele fraction needed to identify clonal hematopoiesis? At what point is CH not CH?
Dr. Viny: So this is as much a technical question as it is a biological question. As of now we can reliably detect variant allele fraction in CH to 0.1%, at best. What is detectable and what is clinically relevant are questions that still need to be answered.
Question: There seems to be a lot of good research going on in CH. What are the big knowledge gaps that future studies should be targeting?
Dr. Viny: First, what are the functional and molecular consequences of the varying alleles in CH? Second, are there other clinical risks to CH beyond leukemia and cardiovascular disease? And third, does inflammation cause CH or does CH cause inflammation?
Dr. Viny is with the Memorial Sloan Kettering Cancer Center, New York, where he is a clinical instructor; is on the staff of the leukemia service; and is a clinical researcher in the Ross Levine Lab. Connect with him on Twitter at @TheDoctorIsVin.
NSAID use early in pregnancy increases miscarriage risk
and a statistically significant dose-response relationship in which the risk increased at a greater duration of exposure was established in a case-control study published in the American Journal of Obstetrics and Gynecology.
The cohorts in the study were NSAID users, acetaminophen-only users, and controls exposed to neither NSAIDs or acetaminophen. The reasoning for including the acetaminophen cohort is that the drug has a similar indication but does not inhibit prostaglandin biosynthesis, as NSAIDs do. Prostaglandin is important for implantation in early pregnancy. The basic facts of what NSAIDs do and how implantation works have led to theories about miscarriage risk, but previous studies have not been conclusive, said De-Kun Li, MD, PhD, of Kaiser Permanente, and his coauthors.
Participants were women in the Kaiser Permanente Northern California database with positive pregnancy test results, questioned by interviewers and compared with pharmacy records when available. The total was 241 women exposed to NSAIDs, 391 exposed to acetaminophen, and 465 unexposed controls.
The adjusted hazard ratio for miscarriage was 1.59 for NSAID users of any timing and any duration, compared with 1.10 for acetaminophen users. If the NSAID exposure first occurred within the first 2 weeks of gestational age, that risk was a 1.89 hazard ratio, and increased to 2.10 when the duration of the near-conception exposure was greater than 14 days. The risk of miscarriage associated with NSAIDs had statistical significance within the first 8 weeks of gestational age, but not later.
“The timing of NSAID use (around conception) and the timing of miscarriage (early miscarriage only) are consistent with the underlying mechanism of the association,” wrote Dr. Li and his associates. The results “provide consistent findings as well as a coherent biological mechanism for the observation.”
The authors warned that the risk “remains largely ignored by both pregnant women and clinicians,” as NSAIDs are still widely prescribed and used.
“The risk was largely confined to women who were not overweight (body mass index less than 25). In contrast, there was little evidence of increased risk of miscarriage due to NSAID use among women who were overweight (body mass index greater than or equal to 25), thus indicating a potential mitigating effect of being overweight,” although this findings requires confirmation, Dr. Li and his associates said.
The study was funded by the National Institute of Child Health and Human Development. The authors reported no conflicts of interest.
SOURCE: Li DK et al. Am J Obstet Gynecol. 2018 Jun. doi: 10.1016/j.ajog.2018.06.002.
and a statistically significant dose-response relationship in which the risk increased at a greater duration of exposure was established in a case-control study published in the American Journal of Obstetrics and Gynecology.
The cohorts in the study were NSAID users, acetaminophen-only users, and controls exposed to neither NSAIDs or acetaminophen. The reasoning for including the acetaminophen cohort is that the drug has a similar indication but does not inhibit prostaglandin biosynthesis, as NSAIDs do. Prostaglandin is important for implantation in early pregnancy. The basic facts of what NSAIDs do and how implantation works have led to theories about miscarriage risk, but previous studies have not been conclusive, said De-Kun Li, MD, PhD, of Kaiser Permanente, and his coauthors.
Participants were women in the Kaiser Permanente Northern California database with positive pregnancy test results, questioned by interviewers and compared with pharmacy records when available. The total was 241 women exposed to NSAIDs, 391 exposed to acetaminophen, and 465 unexposed controls.
The adjusted hazard ratio for miscarriage was 1.59 for NSAID users of any timing and any duration, compared with 1.10 for acetaminophen users. If the NSAID exposure first occurred within the first 2 weeks of gestational age, that risk was a 1.89 hazard ratio, and increased to 2.10 when the duration of the near-conception exposure was greater than 14 days. The risk of miscarriage associated with NSAIDs had statistical significance within the first 8 weeks of gestational age, but not later.
“The timing of NSAID use (around conception) and the timing of miscarriage (early miscarriage only) are consistent with the underlying mechanism of the association,” wrote Dr. Li and his associates. The results “provide consistent findings as well as a coherent biological mechanism for the observation.”
The authors warned that the risk “remains largely ignored by both pregnant women and clinicians,” as NSAIDs are still widely prescribed and used.
“The risk was largely confined to women who were not overweight (body mass index less than 25). In contrast, there was little evidence of increased risk of miscarriage due to NSAID use among women who were overweight (body mass index greater than or equal to 25), thus indicating a potential mitigating effect of being overweight,” although this findings requires confirmation, Dr. Li and his associates said.
The study was funded by the National Institute of Child Health and Human Development. The authors reported no conflicts of interest.
SOURCE: Li DK et al. Am J Obstet Gynecol. 2018 Jun. doi: 10.1016/j.ajog.2018.06.002.
and a statistically significant dose-response relationship in which the risk increased at a greater duration of exposure was established in a case-control study published in the American Journal of Obstetrics and Gynecology.
The cohorts in the study were NSAID users, acetaminophen-only users, and controls exposed to neither NSAIDs or acetaminophen. The reasoning for including the acetaminophen cohort is that the drug has a similar indication but does not inhibit prostaglandin biosynthesis, as NSAIDs do. Prostaglandin is important for implantation in early pregnancy. The basic facts of what NSAIDs do and how implantation works have led to theories about miscarriage risk, but previous studies have not been conclusive, said De-Kun Li, MD, PhD, of Kaiser Permanente, and his coauthors.
Participants were women in the Kaiser Permanente Northern California database with positive pregnancy test results, questioned by interviewers and compared with pharmacy records when available. The total was 241 women exposed to NSAIDs, 391 exposed to acetaminophen, and 465 unexposed controls.
The adjusted hazard ratio for miscarriage was 1.59 for NSAID users of any timing and any duration, compared with 1.10 for acetaminophen users. If the NSAID exposure first occurred within the first 2 weeks of gestational age, that risk was a 1.89 hazard ratio, and increased to 2.10 when the duration of the near-conception exposure was greater than 14 days. The risk of miscarriage associated with NSAIDs had statistical significance within the first 8 weeks of gestational age, but not later.
“The timing of NSAID use (around conception) and the timing of miscarriage (early miscarriage only) are consistent with the underlying mechanism of the association,” wrote Dr. Li and his associates. The results “provide consistent findings as well as a coherent biological mechanism for the observation.”
The authors warned that the risk “remains largely ignored by both pregnant women and clinicians,” as NSAIDs are still widely prescribed and used.
“The risk was largely confined to women who were not overweight (body mass index less than 25). In contrast, there was little evidence of increased risk of miscarriage due to NSAID use among women who were overweight (body mass index greater than or equal to 25), thus indicating a potential mitigating effect of being overweight,” although this findings requires confirmation, Dr. Li and his associates said.
The study was funded by the National Institute of Child Health and Human Development. The authors reported no conflicts of interest.
SOURCE: Li DK et al. Am J Obstet Gynecol. 2018 Jun. doi: 10.1016/j.ajog.2018.06.002.
FROM THE AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Key clinical point: A cohort study in California showed a dose-response relationship between NSAID use early in pregnancy and risk of miscarriage.
Major finding: The adjusted hazard ratio for miscarriage was 1.59 for NSAID users of any timing and any duration, compared with 1.10 for acetaminophen users.
Study details: The study comprised 241 women exposed to NSAIDs, 391 exposed to acetaminophen, and 465 unexposed controls, drawn from the Kaiser Permanente Northern California database.
Disclosures: The National Institute of Child Health and Human Development funded the work. The authors reported no conflicts of interest.
Source: Li DK et al. Am J Obstet Gynecol. 2018 Jun. doi: 10.1016/j.ajog.2018.06.002.
Registry data provide evidence that Mohs surgery remains underutilized
CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the , Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.
Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.
“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”
Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.
His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.
“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.
Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.
Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.
“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.
He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.
“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.
He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.
Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.
CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the , Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.
Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.
“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”
Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.
His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.
“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.
Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.
Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.
“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.
He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.
“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.
He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.
Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.
CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the , Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.
Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.
“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”
Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.
His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.
“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.
Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.
Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.
“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.
He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.
“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.
He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.
Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.
REPORTING FROM THE ACMS 50TH ANNUAL MEETING
Key clinical point: Mohs micrographic surgery remains seriously underutilized for the skin cancers for which it is most advantageous.
Major finding: The use of Mohs micrographic surgery to treat melanoma in situ declined significantly after passage of the Affordable Care Act.
Study details: This was a retrospective study of national SEER data on more than 25,000 patients treated for melanoma in situ or rare cutaneous malignancies during 2008-2014.
Disclosures: The presenter reported having no financial conflicts regarding his study, conducted free of commercial support.
Addressing malnutrition and improving performance
Stakeholders develop a malnutrition Toolkit
Hospitalists are key players in improving hospital performance, but they may be overlooking a leading cause of morbidity and mortality, especially among older adults.
Research suggests that at the time of hospital admission, some 20%-50% of all patients are at risk for malnutrition or are malnourished, but only 7% of those patients are diagnosed during their stay, according to research cited in an abstract presented at HM17.1
“Because individuals who are malnourished lack sufficient nutrients to promote healing and rehabilitation, and are at increased risk of medical complications, it can have a serious impact on patient safety indicators, such as rates of pressure ulcers, wound healing, and risk of falls,” said lead author Eleanor Fitall of Avalere Health. “Early identification and subsequent treatment of these patients is the best way to prevent this risk.”
To address the issue, Avalere Health and the Academy of Nutrition and Dietetics established the Malnutrition Quality Improvement Initiative (MQii), a multi-stakeholder effort to identify tools to support hospital-based care teams in improving malnutrition care quality. They developed a malnutrition Toolkit, which was piloted in 2016 and was shown to effectively improve malnutrition care.
“Since the poster presentation in May, we have successfully implemented the Toolkit at 50 hospitals via a multi-hospital Learning Collaborative,” Ms. Fitall said. They are now recruiting hospitals and health systems to participate in an expanded Learning Collaborative. Interested sites should contact the MQii team at MalnutritionQuality@avalere.com.
“By supporting efforts to improve malnutrition care in the inpatient setting, hospitalists can help reduce the incidence of these problems as well as decrease rates of readmissions and reduce patient lengths of stay,” Ms. Fitall said. “Hospitalists are critical to addressing malnutrition care gaps in the hospital. Dietitians that have undertaken malnutrition quality improvement projects using the MQii Toolkit have found that they are most successful when hospitalists are actively engaged in the team, particularly when looking to improve the rate of malnutrition diagnosis. Hospitalists are ideally positioned to champion these efforts.”
Support for MQii was provided by Abbott, she said.
Reference
1. Fitall E, Bruno M, Jones K, Lynch J, Silver H, Godamunne K, Valladares A, Mitchell K. Malnutrition Care: “Low Hanging Fruit” for Hospitalist Clinical Performance Improvement [abstract]. J Hosp Med. 2017;12(suppl 2).
Stakeholders develop a malnutrition Toolkit
Stakeholders develop a malnutrition Toolkit
Hospitalists are key players in improving hospital performance, but they may be overlooking a leading cause of morbidity and mortality, especially among older adults.
Research suggests that at the time of hospital admission, some 20%-50% of all patients are at risk for malnutrition or are malnourished, but only 7% of those patients are diagnosed during their stay, according to research cited in an abstract presented at HM17.1
“Because individuals who are malnourished lack sufficient nutrients to promote healing and rehabilitation, and are at increased risk of medical complications, it can have a serious impact on patient safety indicators, such as rates of pressure ulcers, wound healing, and risk of falls,” said lead author Eleanor Fitall of Avalere Health. “Early identification and subsequent treatment of these patients is the best way to prevent this risk.”
To address the issue, Avalere Health and the Academy of Nutrition and Dietetics established the Malnutrition Quality Improvement Initiative (MQii), a multi-stakeholder effort to identify tools to support hospital-based care teams in improving malnutrition care quality. They developed a malnutrition Toolkit, which was piloted in 2016 and was shown to effectively improve malnutrition care.
“Since the poster presentation in May, we have successfully implemented the Toolkit at 50 hospitals via a multi-hospital Learning Collaborative,” Ms. Fitall said. They are now recruiting hospitals and health systems to participate in an expanded Learning Collaborative. Interested sites should contact the MQii team at MalnutritionQuality@avalere.com.
“By supporting efforts to improve malnutrition care in the inpatient setting, hospitalists can help reduce the incidence of these problems as well as decrease rates of readmissions and reduce patient lengths of stay,” Ms. Fitall said. “Hospitalists are critical to addressing malnutrition care gaps in the hospital. Dietitians that have undertaken malnutrition quality improvement projects using the MQii Toolkit have found that they are most successful when hospitalists are actively engaged in the team, particularly when looking to improve the rate of malnutrition diagnosis. Hospitalists are ideally positioned to champion these efforts.”
Support for MQii was provided by Abbott, she said.
Reference
1. Fitall E, Bruno M, Jones K, Lynch J, Silver H, Godamunne K, Valladares A, Mitchell K. Malnutrition Care: “Low Hanging Fruit” for Hospitalist Clinical Performance Improvement [abstract]. J Hosp Med. 2017;12(suppl 2).
Hospitalists are key players in improving hospital performance, but they may be overlooking a leading cause of morbidity and mortality, especially among older adults.
Research suggests that at the time of hospital admission, some 20%-50% of all patients are at risk for malnutrition or are malnourished, but only 7% of those patients are diagnosed during their stay, according to research cited in an abstract presented at HM17.1
“Because individuals who are malnourished lack sufficient nutrients to promote healing and rehabilitation, and are at increased risk of medical complications, it can have a serious impact on patient safety indicators, such as rates of pressure ulcers, wound healing, and risk of falls,” said lead author Eleanor Fitall of Avalere Health. “Early identification and subsequent treatment of these patients is the best way to prevent this risk.”
To address the issue, Avalere Health and the Academy of Nutrition and Dietetics established the Malnutrition Quality Improvement Initiative (MQii), a multi-stakeholder effort to identify tools to support hospital-based care teams in improving malnutrition care quality. They developed a malnutrition Toolkit, which was piloted in 2016 and was shown to effectively improve malnutrition care.
“Since the poster presentation in May, we have successfully implemented the Toolkit at 50 hospitals via a multi-hospital Learning Collaborative,” Ms. Fitall said. They are now recruiting hospitals and health systems to participate in an expanded Learning Collaborative. Interested sites should contact the MQii team at MalnutritionQuality@avalere.com.
“By supporting efforts to improve malnutrition care in the inpatient setting, hospitalists can help reduce the incidence of these problems as well as decrease rates of readmissions and reduce patient lengths of stay,” Ms. Fitall said. “Hospitalists are critical to addressing malnutrition care gaps in the hospital. Dietitians that have undertaken malnutrition quality improvement projects using the MQii Toolkit have found that they are most successful when hospitalists are actively engaged in the team, particularly when looking to improve the rate of malnutrition diagnosis. Hospitalists are ideally positioned to champion these efforts.”
Support for MQii was provided by Abbott, she said.
Reference
1. Fitall E, Bruno M, Jones K, Lynch J, Silver H, Godamunne K, Valladares A, Mitchell K. Malnutrition Care: “Low Hanging Fruit” for Hospitalist Clinical Performance Improvement [abstract]. J Hosp Med. 2017;12(suppl 2).
Herpesvirus infections may have a pathogenic link to Alzheimer’s disease
Also today, midlife retinopathy predicts ischemic stroke, fingernails may hold a clue for relapsing scabies, and canakinumab cuts gout attacks by nearly half.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Also today, midlife retinopathy predicts ischemic stroke, fingernails may hold a clue for relapsing scabies, and canakinumab cuts gout attacks by nearly half.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Also today, midlife retinopathy predicts ischemic stroke, fingernails may hold a clue for relapsing scabies, and canakinumab cuts gout attacks by nearly half.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Repurposing With a Purpose
Cryptococcal meningitis is one of the most common mycoses in patients with HIV/AIDS. In developed countries, mortality rates due to the disease hover around 9%—in poor and underdeveloped regions, the number leaps to 70%. Many of those deaths are related to lack of access and difficulty in administering amphotericin B and flucytosine. That is the most effective standard treatment, but it is expensive and carries serious adverse effects, including nephrotoxicity, hepatotoxicity, and bone marrow suppression. Fluconazole, also commonly used, does not effectively clear fungal burden and is associated with clinical relapse.
More antifungals are desperately needed, but it takes billions of dollars to get a drug to market, and the process is slow. Where are the new antifungals to come from? Maybe from other drugs?
Researchers have begun mining drug compound “libraries,” searching for existing drugs that can be repurposed. The drugs have already passed all the regulatory hurdles—it is just a matter of finding which ones could be turned to a new use. The antidepressant sertraline, for instance, has been found to be a potent antifungal that works synergistically with fluconazole and is now being repurposed for cryptococcal meningitis.
Researchers from University of Technology Sydney screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. The search turned up promising results for the anthelminthic agent flubendazole, as well as the L-type calcium channel blockers nifedipine, nisoldipine, and felodipine. Flubendazole was very active against all pathogenic Cryptococcus species, and, importantly, was equally effective against isolates resistant to fluconazole. Nifedipine, nisoldipine and felodipine inhibited Cryptococcus. Nisoldipine was also effective against Candida, Saccharomyces and Aspergillus.
The researchers say flubendazole may be the best starting point for treating cryptococcal disease, both for its effectiveness and because research has not found serious adverse effects from antihelminthic treatment. Flubendazole interferes with normal cell growth as early as 3 hours posttreatment and continues to render treated Cryptococcus cells unviable. However, because flubendazole is formulated to treat gastrointestinal worms, it is not yet known whether it would be able to reach therapeutic concentrations in the brain required for an antifungal effect.
Overall, their findings, the researchers say, “validates repurposing as a rapid approach for finding new agents to treat neglected infectious diseases.”
Source:
Truong M, Monahan LG, Carter DA, Charles IG. PeerJ. 2018;6: e4761.
doi: 10.7717/peerj.4761
Cryptococcal meningitis is one of the most common mycoses in patients with HIV/AIDS. In developed countries, mortality rates due to the disease hover around 9%—in poor and underdeveloped regions, the number leaps to 70%. Many of those deaths are related to lack of access and difficulty in administering amphotericin B and flucytosine. That is the most effective standard treatment, but it is expensive and carries serious adverse effects, including nephrotoxicity, hepatotoxicity, and bone marrow suppression. Fluconazole, also commonly used, does not effectively clear fungal burden and is associated with clinical relapse.
More antifungals are desperately needed, but it takes billions of dollars to get a drug to market, and the process is slow. Where are the new antifungals to come from? Maybe from other drugs?
Researchers have begun mining drug compound “libraries,” searching for existing drugs that can be repurposed. The drugs have already passed all the regulatory hurdles—it is just a matter of finding which ones could be turned to a new use. The antidepressant sertraline, for instance, has been found to be a potent antifungal that works synergistically with fluconazole and is now being repurposed for cryptococcal meningitis.
Researchers from University of Technology Sydney screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. The search turned up promising results for the anthelminthic agent flubendazole, as well as the L-type calcium channel blockers nifedipine, nisoldipine, and felodipine. Flubendazole was very active against all pathogenic Cryptococcus species, and, importantly, was equally effective against isolates resistant to fluconazole. Nifedipine, nisoldipine and felodipine inhibited Cryptococcus. Nisoldipine was also effective against Candida, Saccharomyces and Aspergillus.
The researchers say flubendazole may be the best starting point for treating cryptococcal disease, both for its effectiveness and because research has not found serious adverse effects from antihelminthic treatment. Flubendazole interferes with normal cell growth as early as 3 hours posttreatment and continues to render treated Cryptococcus cells unviable. However, because flubendazole is formulated to treat gastrointestinal worms, it is not yet known whether it would be able to reach therapeutic concentrations in the brain required for an antifungal effect.
Overall, their findings, the researchers say, “validates repurposing as a rapid approach for finding new agents to treat neglected infectious diseases.”
Source:
Truong M, Monahan LG, Carter DA, Charles IG. PeerJ. 2018;6: e4761.
doi: 10.7717/peerj.4761
Cryptococcal meningitis is one of the most common mycoses in patients with HIV/AIDS. In developed countries, mortality rates due to the disease hover around 9%—in poor and underdeveloped regions, the number leaps to 70%. Many of those deaths are related to lack of access and difficulty in administering amphotericin B and flucytosine. That is the most effective standard treatment, but it is expensive and carries serious adverse effects, including nephrotoxicity, hepatotoxicity, and bone marrow suppression. Fluconazole, also commonly used, does not effectively clear fungal burden and is associated with clinical relapse.
More antifungals are desperately needed, but it takes billions of dollars to get a drug to market, and the process is slow. Where are the new antifungals to come from? Maybe from other drugs?
Researchers have begun mining drug compound “libraries,” searching for existing drugs that can be repurposed. The drugs have already passed all the regulatory hurdles—it is just a matter of finding which ones could be turned to a new use. The antidepressant sertraline, for instance, has been found to be a potent antifungal that works synergistically with fluconazole and is now being repurposed for cryptococcal meningitis.
Researchers from University of Technology Sydney screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. The search turned up promising results for the anthelminthic agent flubendazole, as well as the L-type calcium channel blockers nifedipine, nisoldipine, and felodipine. Flubendazole was very active against all pathogenic Cryptococcus species, and, importantly, was equally effective against isolates resistant to fluconazole. Nifedipine, nisoldipine and felodipine inhibited Cryptococcus. Nisoldipine was also effective against Candida, Saccharomyces and Aspergillus.
The researchers say flubendazole may be the best starting point for treating cryptococcal disease, both for its effectiveness and because research has not found serious adverse effects from antihelminthic treatment. Flubendazole interferes with normal cell growth as early as 3 hours posttreatment and continues to render treated Cryptococcus cells unviable. However, because flubendazole is formulated to treat gastrointestinal worms, it is not yet known whether it would be able to reach therapeutic concentrations in the brain required for an antifungal effect.
Overall, their findings, the researchers say, “validates repurposing as a rapid approach for finding new agents to treat neglected infectious diseases.”
Source:
Truong M, Monahan LG, Carter DA, Charles IG. PeerJ. 2018;6: e4761.
doi: 10.7717/peerj.4761