SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.

ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.

“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).

That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”

ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.

ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.

The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.

To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.

Dr. Pagnoux had no financial disclosures relevant to either study.

[email protected]

SOURCE: Pagnoux C. CCR 2018

SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.

ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.

“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).

That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”

ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.

ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.

The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.

To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.

Dr. Pagnoux had no financial disclosures relevant to either study.

[email protected]

SOURCE: Pagnoux C. CCR 2018

SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.

ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.

“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).

That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”

ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.

ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.

The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.

To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.

Dr. Pagnoux had no financial disclosures relevant to either study.

[email protected]

SOURCE: Pagnoux C. CCR 2018

SANDESTIN, FLA. – Big data informing patient treatment, computer algorithms reading imaging instead of humans, and even accurate patient self-diagnosis could emerge over the next 10 years in the treatment of rheumatoid arthritis, an expert said at the annual Congress of Clinical Rheumatology.

Gerd Burmester, MD, director of rheumatology and clinical immunology at Charité University in Berlin, trotted out staggering numbers on future medical data collection on patients. Data analytics companies project that more than 1,000 terabytes of data per lifetime is expected to be gathered, with just 10% expected to be clinical information and 30% in the form of “-omics,” such as proteomics and genomics, he said. The other 60% is expected to come from sensors and wearables that patients essentially collect themselves with their own devices, he said.

“We will have to use data in the interest of the patient,” he said. “This is the real secret. In order to do this, we need cognitive computing, which assesses structured and unstructured data and is self-learning.”

The days of images being read by human radiologists could be numbered, he said.

“There will be a revolution in imaging scoring,” he said, with computer algorithms generating scores, more quickly separating the normal scans from those that need clinical attention.

He described a possible scenario in which patients get genetic analyses, blood biomarker testing, and imaging performed at kiosks about town, producing a diagnosis without a single physician visit. It might seem fanciful, but when he asked the audience how many thought it was impossible over the next decade, no one raised a hand.

With advances such as the self-rheumatoid arthritis examination tool Rheuma-Check and the decline in cost for whole genome sequencing – along with wait times to see rheumatologists sometimes as long as 6 months – such a scenario might not be far fetched, Dr. Burmester said. It is possible, he said, because patient histories that used to sit in charts, images that used to be on film only, and genetic data that used to be unavailable, are all now in structured, digital form.

Referring to a recent commentary in the New England Journal of Medicine, Dr. Burmester said physicians have to accept the coming role of computer algorithms.

“If medicine wishes to stay in control of its own future,” he said, “physicians will not only have to embrace algorithms, they will also have to excel at developing and evaluating them, bringing machine-learning methods into the medical domain.”

SOURCE: Burmester, G. CCR 2018.

SANDESTIN, FLA. – Big data informing patient treatment, computer algorithms reading imaging instead of humans, and even accurate patient self-diagnosis could emerge over the next 10 years in the treatment of rheumatoid arthritis, an expert said at the annual Congress of Clinical Rheumatology.

Gerd Burmester, MD, director of rheumatology and clinical immunology at Charité University in Berlin, trotted out staggering numbers on future medical data collection on patients. Data analytics companies project that more than 1,000 terabytes of data per lifetime is expected to be gathered, with just 10% expected to be clinical information and 30% in the form of “-omics,” such as proteomics and genomics, he said. The other 60% is expected to come from sensors and wearables that patients essentially collect themselves with their own devices, he said.

“We will have to use data in the interest of the patient,” he said. “This is the real secret. In order to do this, we need cognitive computing, which assesses structured and unstructured data and is self-learning.”

The days of images being read by human radiologists could be numbered, he said.

“There will be a revolution in imaging scoring,” he said, with computer algorithms generating scores, more quickly separating the normal scans from those that need clinical attention.

He described a possible scenario in which patients get genetic analyses, blood biomarker testing, and imaging performed at kiosks about town, producing a diagnosis without a single physician visit. It might seem fanciful, but when he asked the audience how many thought it was impossible over the next decade, no one raised a hand.

With advances such as the self-rheumatoid arthritis examination tool Rheuma-Check and the decline in cost for whole genome sequencing – along with wait times to see rheumatologists sometimes as long as 6 months – such a scenario might not be far fetched, Dr. Burmester said. It is possible, he said, because patient histories that used to sit in charts, images that used to be on film only, and genetic data that used to be unavailable, are all now in structured, digital form.

Referring to a recent commentary in the New England Journal of Medicine, Dr. Burmester said physicians have to accept the coming role of computer algorithms.

“If medicine wishes to stay in control of its own future,” he said, “physicians will not only have to embrace algorithms, they will also have to excel at developing and evaluating them, bringing machine-learning methods into the medical domain.”

SOURCE: Burmester, G. CCR 2018.

SANDESTIN, FLA. – Big data informing patient treatment, computer algorithms reading imaging instead of humans, and even accurate patient self-diagnosis could emerge over the next 10 years in the treatment of rheumatoid arthritis, an expert said at the annual Congress of Clinical Rheumatology.

Gerd Burmester, MD, director of rheumatology and clinical immunology at Charité University in Berlin, trotted out staggering numbers on future medical data collection on patients. Data analytics companies project that more than 1,000 terabytes of data per lifetime is expected to be gathered, with just 10% expected to be clinical information and 30% in the form of “-omics,” such as proteomics and genomics, he said. The other 60% is expected to come from sensors and wearables that patients essentially collect themselves with their own devices, he said.

“We will have to use data in the interest of the patient,” he said. “This is the real secret. In order to do this, we need cognitive computing, which assesses structured and unstructured data and is self-learning.”

The days of images being read by human radiologists could be numbered, he said.

“There will be a revolution in imaging scoring,” he said, with computer algorithms generating scores, more quickly separating the normal scans from those that need clinical attention.

He described a possible scenario in which patients get genetic analyses, blood biomarker testing, and imaging performed at kiosks about town, producing a diagnosis without a single physician visit. It might seem fanciful, but when he asked the audience how many thought it was impossible over the next decade, no one raised a hand.

With advances such as the self-rheumatoid arthritis examination tool Rheuma-Check and the decline in cost for whole genome sequencing – along with wait times to see rheumatologists sometimes as long as 6 months – such a scenario might not be far fetched, Dr. Burmester said. It is possible, he said, because patient histories that used to sit in charts, images that used to be on film only, and genetic data that used to be unavailable, are all now in structured, digital form.

Referring to a recent commentary in the New England Journal of Medicine, Dr. Burmester said physicians have to accept the coming role of computer algorithms.

“If medicine wishes to stay in control of its own future,” he said, “physicians will not only have to embrace algorithms, they will also have to excel at developing and evaluating them, bringing machine-learning methods into the medical domain.”

SOURCE: Burmester, G. CCR 2018.

In today’s edition of the Daily News Podcast, heart rate variability may be a risk factor for depression, not a consequence of it. Also, results of the SYGMA1 and SYGMA1 trials show that as-needed budesonide-formoterol prevented exacerbations in mild asthma, patients with Parkinson’s disease may have impaired insulin secretion, and FDA commissioner Scott Gottlieb floats ideas on Medicare drug coverage. Listen to the MDedge Daily News podcast for all the details on today’s top news.

In today’s edition of the Daily News Podcast, heart rate variability may be a risk factor for depression, not a consequence of it. Also, results of the SYGMA1 and SYGMA1 trials show that as-needed budesonide-formoterol prevented exacerbations in mild asthma, patients with Parkinson’s disease may have impaired insulin secretion, and FDA commissioner Scott Gottlieb floats ideas on Medicare drug coverage. Listen to the MDedge Daily News podcast for all the details on today’s top news.

In today’s edition of the Daily News Podcast, heart rate variability may be a risk factor for depression, not a consequence of it. Also, results of the SYGMA1 and SYGMA1 trials show that as-needed budesonide-formoterol prevented exacerbations in mild asthma, patients with Parkinson’s disease may have impaired insulin secretion, and FDA commissioner Scott Gottlieb floats ideas on Medicare drug coverage. Listen to the MDedge Daily News podcast for all the details on today’s top news.

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Lab mouse

Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).

Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.

However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.

Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.

The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.

However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.

With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.

The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.

The researchers found they could induce PMP in symptom-free Tet2^−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.

However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2^−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.

Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.

Lab mouse

Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).

Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.

However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.

Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.

The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.

However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.

With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.

The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.

The researchers found they could induce PMP in symptom-free Tet2^−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.

However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2^−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.

Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.

Lab mouse

Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).

Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.

However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.

Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.

The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.

However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.

With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.

The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.

The researchers found they could induce PMP in symptom-free Tet2^−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.

However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2^−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.

Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.

Photo by Darren Baker

Electronic health records (EHRs) can enhance results from randomized controlled trials (RCTs), according to research published in Scientific Reports.

Researchers found EHRs could be used to track trial participants, enabling long-term monitoring of medical interventions and health outcomes and providing new insights into population health.

“In this study, we reported on the feasibility and efficiency of electronic follow-up and compared it with traditional trial follow-up,” said study author Sue Jordan, PhD, MB BCh, of Swansea University in Swansea, UK.

“We gained new insights from outcomes electronically recorded 3 years after the end of the trial and could then identify the differences between trial data and electronic data.”

Dr Jordan and her colleagues followed up on RCT participants using EHRs in the Secure Anonymised Information Linkage (SAIL) databank at Swansea University Medical School.

In this RCT, investigators had assessed the impact of probiotics on asthma and eczema in children born from 2005 to 2007. The trial had 2 years of traditional fieldwork follow-up.

Dr Jordan and her colleagues compared field results to EHR results at 2 years in 93% of trial participants.

The researchers said EHRs improved retention of children from lower socio-economic groups, which helped reduce volunteer bias.

The team also performed electronic follow-up at 5 years, which provided the “first robust analysis of asthma endpoints.”

The researchers said the asthma endpoints are “generally more reliable” in the 5-year EHR data for 2 reasons. The first is that the children are older, and asthma typically appears after 2 years of age.

The second reason is that, with the fieldwork follow-up, parents or guardians may have mistakenly identified symptoms as asthma without a child actually having an asthma diagnosis.

“Trial data are vulnerable to misunderstandings of questionnaires or definitions of illness,” Dr Jordan noted.

She and her colleagues also pointed out that retention was still high (82%) and free of bias in socio-economic status with the 5-year EHR data.

“These results lead us to conclude that using electronic health records have benefits relating to the cost-effective, long-term monitoring of complex interventions, which could have a positive impact for future clinical trial design,” said study author Michael Gravenor, DPhil, of Swansea University.

Photo by Darren Baker

Electronic health records (EHRs) can enhance results from randomized controlled trials (RCTs), according to research published in Scientific Reports.

Researchers found EHRs could be used to track trial participants, enabling long-term monitoring of medical interventions and health outcomes and providing new insights into population health.

“In this study, we reported on the feasibility and efficiency of electronic follow-up and compared it with traditional trial follow-up,” said study author Sue Jordan, PhD, MB BCh, of Swansea University in Swansea, UK.

“We gained new insights from outcomes electronically recorded 3 years after the end of the trial and could then identify the differences between trial data and electronic data.”

Dr Jordan and her colleagues followed up on RCT participants using EHRs in the Secure Anonymised Information Linkage (SAIL) databank at Swansea University Medical School.

In this RCT, investigators had assessed the impact of probiotics on asthma and eczema in children born from 2005 to 2007. The trial had 2 years of traditional fieldwork follow-up.

Dr Jordan and her colleagues compared field results to EHR results at 2 years in 93% of trial participants.

The researchers said EHRs improved retention of children from lower socio-economic groups, which helped reduce volunteer bias.

The team also performed electronic follow-up at 5 years, which provided the “first robust analysis of asthma endpoints.”

The researchers said the asthma endpoints are “generally more reliable” in the 5-year EHR data for 2 reasons. The first is that the children are older, and asthma typically appears after 2 years of age.

The second reason is that, with the fieldwork follow-up, parents or guardians may have mistakenly identified symptoms as asthma without a child actually having an asthma diagnosis.

“Trial data are vulnerable to misunderstandings of questionnaires or definitions of illness,” Dr Jordan noted.

She and her colleagues also pointed out that retention was still high (82%) and free of bias in socio-economic status with the 5-year EHR data.

“These results lead us to conclude that using electronic health records have benefits relating to the cost-effective, long-term monitoring of complex interventions, which could have a positive impact for future clinical trial design,” said study author Michael Gravenor, DPhil, of Swansea University.

Photo by Darren Baker

Electronic health records (EHRs) can enhance results from randomized controlled trials (RCTs), according to research published in Scientific Reports.

Researchers found EHRs could be used to track trial participants, enabling long-term monitoring of medical interventions and health outcomes and providing new insights into population health.

“In this study, we reported on the feasibility and efficiency of electronic follow-up and compared it with traditional trial follow-up,” said study author Sue Jordan, PhD, MB BCh, of Swansea University in Swansea, UK.

“We gained new insights from outcomes electronically recorded 3 years after the end of the trial and could then identify the differences between trial data and electronic data.”

Dr Jordan and her colleagues followed up on RCT participants using EHRs in the Secure Anonymised Information Linkage (SAIL) databank at Swansea University Medical School.

In this RCT, investigators had assessed the impact of probiotics on asthma and eczema in children born from 2005 to 2007. The trial had 2 years of traditional fieldwork follow-up.

Dr Jordan and her colleagues compared field results to EHR results at 2 years in 93% of trial participants.

The researchers said EHRs improved retention of children from lower socio-economic groups, which helped reduce volunteer bias.

The team also performed electronic follow-up at 5 years, which provided the “first robust analysis of asthma endpoints.”

The researchers said the asthma endpoints are “generally more reliable” in the 5-year EHR data for 2 reasons. The first is that the children are older, and asthma typically appears after 2 years of age.

The second reason is that, with the fieldwork follow-up, parents or guardians may have mistakenly identified symptoms as asthma without a child actually having an asthma diagnosis.

“Trial data are vulnerable to misunderstandings of questionnaires or definitions of illness,” Dr Jordan noted.

She and her colleagues also pointed out that retention was still high (82%) and free of bias in socio-economic status with the 5-year EHR data.

“These results lead us to conclude that using electronic health records have benefits relating to the cost-effective, long-term monitoring of complex interventions, which could have a positive impact for future clinical trial design,” said study author Michael Gravenor, DPhil, of Swansea University.

Martinez, K.A., et al, Am J Prev Med 53(4):533, October 2017

The authors, from the Cleveland Clinic, explore the reasons for divergent responses to recent guideline recommendations against screening for breast cancer and prostate cancer. Both cancers are common (lifetime incidence of 12% and 16%, respectively), with indolent forms that are more prevalent with age. Screening with mammography and prostate-specific antigen (PSA) testing achieves earlier detection and relative risk reductions in cancer-specific mortality of 15% to 20%, but negligible effects on overall mortality and a risk of overtreatment that is estimated to be 30% to 80%. Benefits of screening and risks of overtreatment are unclear because of study limitations and evolution in diagnostic criteria, screening and management. Beginning in 2008, the US Preventive Services Task Force downgraded its recommendations for routine mammography (e.g., a rating of C for average-risk women aged 40-49) and for routine PSA testing (rating of D regardless of age). [EDITOR’S NOTE: USPSTF PSA screening recommendations have changed. See “USPSTF advises against widespread prostate cancer screening.”] While objections to the PSA rating were minimal, the public and professional backlash about mammography was profound. Reasons may include unique characteristics of breast (versus prostate) cancer, including mortality at a younger age, financial conflicts of interest (with mammography generating $8 billion per year in the US), bureaucratic incentives (e.g., quality measures, insurance reimbursement), and the influence of profit-generating advocacy groups. Many physicians do not understand the risks and harms of overtreatment or the inability of early detection to prevent metastasis, and patients want to be “better safe than sorry.” Rates of screening mammography may not decrease until truly informed decisions are possible, which will necessitate better algorithms to predict those cancers that are likely to spread.  20 references ([email protected] – no reprints)

Martinez, K.A., et al, Am J Prev Med 53(4):533, October 2017

The authors, from the Cleveland Clinic, explore the reasons for divergent responses to recent guideline recommendations against screening for breast cancer and prostate cancer. Both cancers are common (lifetime incidence of 12% and 16%, respectively), with indolent forms that are more prevalent with age. Screening with mammography and prostate-specific antigen (PSA) testing achieves earlier detection and relative risk reductions in cancer-specific mortality of 15% to 20%, but negligible effects on overall mortality and a risk of overtreatment that is estimated to be 30% to 80%. Benefits of screening and risks of overtreatment are unclear because of study limitations and evolution in diagnostic criteria, screening and management. Beginning in 2008, the US Preventive Services Task Force downgraded its recommendations for routine mammography (e.g., a rating of C for average-risk women aged 40-49) and for routine PSA testing (rating of D regardless of age). [EDITOR’S NOTE: USPSTF PSA screening recommendations have changed. See “USPSTF advises against widespread prostate cancer screening.”] While objections to the PSA rating were minimal, the public and professional backlash about mammography was profound. Reasons may include unique characteristics of breast (versus prostate) cancer, including mortality at a younger age, financial conflicts of interest (with mammography generating $8 billion per year in the US), bureaucratic incentives (e.g., quality measures, insurance reimbursement), and the influence of profit-generating advocacy groups. Many physicians do not understand the risks and harms of overtreatment or the inability of early detection to prevent metastasis, and patients want to be “better safe than sorry.” Rates of screening mammography may not decrease until truly informed decisions are possible, which will necessitate better algorithms to predict those cancers that are likely to spread.  20 references ([email protected] – no reprints)

Martinez, K.A., et al, Am J Prev Med 53(4):533, October 2017

The authors, from the Cleveland Clinic, explore the reasons for divergent responses to recent guideline recommendations against screening for breast cancer and prostate cancer. Both cancers are common (lifetime incidence of 12% and 16%, respectively), with indolent forms that are more prevalent with age. Screening with mammography and prostate-specific antigen (PSA) testing achieves earlier detection and relative risk reductions in cancer-specific mortality of 15% to 20%, but negligible effects on overall mortality and a risk of overtreatment that is estimated to be 30% to 80%. Benefits of screening and risks of overtreatment are unclear because of study limitations and evolution in diagnostic criteria, screening and management. Beginning in 2008, the US Preventive Services Task Force downgraded its recommendations for routine mammography (e.g., a rating of C for average-risk women aged 40-49) and for routine PSA testing (rating of D regardless of age). [EDITOR’S NOTE: USPSTF PSA screening recommendations have changed. See “USPSTF advises against widespread prostate cancer screening.”] While objections to the PSA rating were minimal, the public and professional backlash about mammography was profound. Reasons may include unique characteristics of breast (versus prostate) cancer, including mortality at a younger age, financial conflicts of interest (with mammography generating $8 billion per year in the US), bureaucratic incentives (e.g., quality measures, insurance reimbursement), and the influence of profit-generating advocacy groups. Many physicians do not understand the risks and harms of overtreatment or the inability of early detection to prevent metastasis, and patients want to be “better safe than sorry.” Rates of screening mammography may not decrease until truly informed decisions are possible, which will necessitate better algorithms to predict those cancers that are likely to spread.  20 references ([email protected] – no reprints)

Clinical question: What guidance is there for clinical care of complex heart failure patients?

Background: The prevalence of heart failure (HF)is escalating and consumes significant health care resources, inflicts significant morbidity and mortality, and greatly affects quality of life. There is a plethora of research, multiple medical therapies, devices, and care strategies that have been shown to improve outcomes in heart failure patients. Previous publications have reviewed evidence-based literature but left a gap in knowledge for those more-complex areas or lacked practical clinical guidance. This policy document was created to guide physicians in informed decision making in a directed decision pathway form.

Study design: Expert consensus guidelines.

Setting: American College of Cardiology Task Force on Expert Consensus Decision Pathways.

Synopsis: A multidisciplinary group of specialties including physicians, nurses, pharmacists, epidemiologists, and patient advocacy groups addressed 10 pivotal issues in heart failure through literature review, expert consensus, and round table discussion.

Ten principles were identified and addressed:

• Initiating, adding, or switching to new evidenced-based guideline-directed therapy.
• Achieving optimal therapy using multiple HF drugs and therapies.
• Knowing when to refer a patient to an HF specialist.
• Addressing the challenges of care coordination for team-based HF treatment.
• Improving patient adherence.
• Managing specific patient cohorts, such as African Americans, older adults, and the frail.
• Managing your patients’ cost of care for HF.
• Reducing costs and managing the increased complexity of HF.
• Managing the most common cardiac and noncardiac comorbidities.
• Integrating palliative care and transitioning patients to hospice care

Bottom line: Structured guidelines to provide practical and actionable recommendations to improve heart failure outcomes, integrate evidence-based medicine when available, and utilize expert conscious when evidence-based medicine is not available.

Citation: Yancy CW et al. 2017 ACC expert consensus on decision pathway for optimizing of heart failure treatment: Answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018 Jan 16;71(2):201-30.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Clinical question: What guidance is there for clinical care of complex heart failure patients?

Background: The prevalence of heart failure (HF)is escalating and consumes significant health care resources, inflicts significant morbidity and mortality, and greatly affects quality of life. There is a plethora of research, multiple medical therapies, devices, and care strategies that have been shown to improve outcomes in heart failure patients. Previous publications have reviewed evidence-based literature but left a gap in knowledge for those more-complex areas or lacked practical clinical guidance. This policy document was created to guide physicians in informed decision making in a directed decision pathway form.

Study design: Expert consensus guidelines.

Setting: American College of Cardiology Task Force on Expert Consensus Decision Pathways.

Synopsis: A multidisciplinary group of specialties including physicians, nurses, pharmacists, epidemiologists, and patient advocacy groups addressed 10 pivotal issues in heart failure through literature review, expert consensus, and round table discussion.

Ten principles were identified and addressed:

• Initiating, adding, or switching to new evidenced-based guideline-directed therapy.
• Achieving optimal therapy using multiple HF drugs and therapies.
• Knowing when to refer a patient to an HF specialist.
• Addressing the challenges of care coordination for team-based HF treatment.
• Improving patient adherence.
• Managing specific patient cohorts, such as African Americans, older adults, and the frail.
• Managing your patients’ cost of care for HF.
• Reducing costs and managing the increased complexity of HF.
• Managing the most common cardiac and noncardiac comorbidities.
• Integrating palliative care and transitioning patients to hospice care

Bottom line: Structured guidelines to provide practical and actionable recommendations to improve heart failure outcomes, integrate evidence-based medicine when available, and utilize expert conscious when evidence-based medicine is not available.

Citation: Yancy CW et al. 2017 ACC expert consensus on decision pathway for optimizing of heart failure treatment: Answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018 Jan 16;71(2):201-30.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Clinical question: What guidance is there for clinical care of complex heart failure patients?

Background: The prevalence of heart failure (HF)is escalating and consumes significant health care resources, inflicts significant morbidity and mortality, and greatly affects quality of life. There is a plethora of research, multiple medical therapies, devices, and care strategies that have been shown to improve outcomes in heart failure patients. Previous publications have reviewed evidence-based literature but left a gap in knowledge for those more-complex areas or lacked practical clinical guidance. This policy document was created to guide physicians in informed decision making in a directed decision pathway form.

Study design: Expert consensus guidelines.

Setting: American College of Cardiology Task Force on Expert Consensus Decision Pathways.

Synopsis: A multidisciplinary group of specialties including physicians, nurses, pharmacists, epidemiologists, and patient advocacy groups addressed 10 pivotal issues in heart failure through literature review, expert consensus, and round table discussion.

Ten principles were identified and addressed:

• Initiating, adding, or switching to new evidenced-based guideline-directed therapy.
• Achieving optimal therapy using multiple HF drugs and therapies.
• Knowing when to refer a patient to an HF specialist.
• Addressing the challenges of care coordination for team-based HF treatment.
• Improving patient adherence.
• Managing specific patient cohorts, such as African Americans, older adults, and the frail.
• Managing your patients’ cost of care for HF.
• Reducing costs and managing the increased complexity of HF.
• Managing the most common cardiac and noncardiac comorbidities.
• Integrating palliative care and transitioning patients to hospice care

Bottom line: Structured guidelines to provide practical and actionable recommendations to improve heart failure outcomes, integrate evidence-based medicine when available, and utilize expert conscious when evidence-based medicine is not available.

Citation: Yancy CW et al. 2017 ACC expert consensus on decision pathway for optimizing of heart failure treatment: Answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018 Jan 16;71(2):201-30.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.

Grigorev_Vladimir/iStock Editorial/Getty Images

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Four more e-cigarette manufacturers are facing Food and Drug Administration scrutiny in an effort for the agency to better understand youth appeal and usage of e-cigarettes.

“Too many kids continue to experiment with e-cigarette and vaping products, putting them at risk for developing a lifelong nicotine addiction,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “These products should never be marketed to, sold to, or used by kids, and it’s critical that we take aggressive steps to address the youth use of these products.”

Thinkstockphotos.com

The May 17 letters note that the four companies manufacture products similar to JUUL’s product offering, sharing similar characteristics, “including e-liquids that contain nicotine salts with corresponding high nicotine concentration, small size which makes them easily concealable, and product design features that are intuitive, even for novice [electronic nicotine delivery system] users. These attributes may relate to the appeal and addictiveness of the product, particularly for youth who may be experimenting with tobacco products.”

The action is the latest in the agency’s effort to combat nicotine addiction. In March, the agency issues an advanced notice of proposed rule making seeking information on the role flavoring plays in youth tobacco consumption.

[email protected]

Four more e-cigarette manufacturers are facing Food and Drug Administration scrutiny in an effort for the agency to better understand youth appeal and usage of e-cigarettes.

“Too many kids continue to experiment with e-cigarette and vaping products, putting them at risk for developing a lifelong nicotine addiction,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “These products should never be marketed to, sold to, or used by kids, and it’s critical that we take aggressive steps to address the youth use of these products.”

Thinkstockphotos.com

The May 17 letters note that the four companies manufacture products similar to JUUL’s product offering, sharing similar characteristics, “including e-liquids that contain nicotine salts with corresponding high nicotine concentration, small size which makes them easily concealable, and product design features that are intuitive, even for novice [electronic nicotine delivery system] users. These attributes may relate to the appeal and addictiveness of the product, particularly for youth who may be experimenting with tobacco products.”

The action is the latest in the agency’s effort to combat nicotine addiction. In March, the agency issues an advanced notice of proposed rule making seeking information on the role flavoring plays in youth tobacco consumption.

[email protected]

Four more e-cigarette manufacturers are facing Food and Drug Administration scrutiny in an effort for the agency to better understand youth appeal and usage of e-cigarettes.

“Too many kids continue to experiment with e-cigarette and vaping products, putting them at risk for developing a lifelong nicotine addiction,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “These products should never be marketed to, sold to, or used by kids, and it’s critical that we take aggressive steps to address the youth use of these products.”

Thinkstockphotos.com

The May 17 letters note that the four companies manufacture products similar to JUUL’s product offering, sharing similar characteristics, “including e-liquids that contain nicotine salts with corresponding high nicotine concentration, small size which makes them easily concealable, and product design features that are intuitive, even for novice [electronic nicotine delivery system] users. These attributes may relate to the appeal and addictiveness of the product, particularly for youth who may be experimenting with tobacco products.”

The action is the latest in the agency’s effort to combat nicotine addiction. In March, the agency issues an advanced notice of proposed rule making seeking information on the role flavoring plays in youth tobacco consumption.

[email protected]