New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

Transtympanic antibiotic delivery

Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.

Biofilms

Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.

Probiotics

The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.

Vaccines

The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.

Biomarkers.

Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.

Overdiagnosis

Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.

Immunity

The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].

New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

Transtympanic antibiotic delivery

Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.

Biofilms

Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.

Probiotics

The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.

Vaccines

The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.

Biomarkers.

Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.

Overdiagnosis

Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.

Immunity

The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].

New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

Transtympanic antibiotic delivery

Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.

Biofilms

Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.

Probiotics

The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.

Vaccines

The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.

Biomarkers.

Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.

Overdiagnosis

Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.

Immunity

The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].

MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).

The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.

Sara Freeman/MDedge News

“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.

“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”

A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.

“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.

Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.

The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.

The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.

The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.

Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”

Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”

The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.

“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”

Dr. Kiltz had no relevant conflicts of interest.

SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.

MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).

The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.

Sara Freeman/MDedge News

“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.

“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”

A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.

“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.

Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.

The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.

The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.

The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.

Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”

Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”

The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.

“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”

Dr. Kiltz had no relevant conflicts of interest.

SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.

MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).

The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.

Sara Freeman/MDedge News

“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.

“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”

A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.

“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.

Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.

The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.

The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.

The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.

Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”

Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”

The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.

“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”

Dr. Kiltz had no relevant conflicts of interest.

SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.

Background: In patients with primary degenerative MR, MVR is curative, with the transcatheter approach being safer than surgical repair. However, it is unknown whether patients with secondary MR from left ventricular dilatation would confer the same benefit of MVR.

Limitations include that investigators were not blinded because the device was visible on imaging. Longer follow-up in the device group may have contributed to the observed decreased mortality. It is unknown whether less-symptomatic patients would attain the same benefit.

Bottom line: In patients with symptomatic, moderate to severe, and severe secondary MR, MVR lowers rates of hospitalization, decreases mortality, and improves quality of life.

Citation: Stone GW et al. Trans­catheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640.
 

Dr. Kochar is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

Background: In patients with primary degenerative MR, MVR is curative, with the transcatheter approach being safer than surgical repair. However, it is unknown whether patients with secondary MR from left ventricular dilatation would confer the same benefit of MVR.

Limitations include that investigators were not blinded because the device was visible on imaging. Longer follow-up in the device group may have contributed to the observed decreased mortality. It is unknown whether less-symptomatic patients would attain the same benefit.

Bottom line: In patients with symptomatic, moderate to severe, and severe secondary MR, MVR lowers rates of hospitalization, decreases mortality, and improves quality of life.

Citation: Stone GW et al. Trans­catheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640.
 

Dr. Kochar is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

Background: In patients with primary degenerative MR, MVR is curative, with the transcatheter approach being safer than surgical repair. However, it is unknown whether patients with secondary MR from left ventricular dilatation would confer the same benefit of MVR.

Limitations include that investigators were not blinded because the device was visible on imaging. Longer follow-up in the device group may have contributed to the observed decreased mortality. It is unknown whether less-symptomatic patients would attain the same benefit.

Bottom line: In patients with symptomatic, moderate to severe, and severe secondary MR, MVR lowers rates of hospitalization, decreases mortality, and improves quality of life.

Citation: Stone GW et al. Trans­catheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640.
 

Dr. Kochar is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.

“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.

The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.

“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.

The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.

“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.

The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

Eraxion/Thinkstock

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues. “Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine. “However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease. The literature search returned 22 eligible studies involving 2,588 patients.

The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

Eraxion/Thinkstock

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues. “Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine. “However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease. The literature search returned 22 eligible studies involving 2,588 patients.

The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.

Eraxion/Thinkstock

The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues. “Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine. “However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.

To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease. The literature search returned 22 eligible studies involving 2,588 patients.

The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I² = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I² = 94%), histologic NAFLD activity score (-0.92; I²= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I² =0%), alanine aminotransferase (-9.81 U/L; I²= 97%), aspartate transaminase (-4.84 U/L; I² = 96%), alkaline phosphatase (-5.53 U/L; I² = 96%), and gamma-glutamyl transferase (-4.35 U/L; I² = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.

“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”

“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.

The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.

SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.

Radioactive iodine therapy for hyperthyroidism may be associated with an increased risk of death from cancer, according to a longitudinal cohort study published in the July 1 issue of JAMA Internal Medicine.

Sebastian Kaulitzki/Fotolia

The study followed 18,805 individuals whose hyperthyroidism was treated with radioactive iodine in the United States and United Kingdom between 1946 and 1964.

Researchers found positive dose-response relationships between radioactive iodine therapy and most of the solid cancers that were evaluated. However these only attained statistical significance in the case of female breast cancer – where there was a 12% increase in the risk of death from breast cancer from a 100-mGy tissue- or organ-absorbed dose – or for all solid cancers combined, where a 100-mGy dose to the stomach was associated with a 6% increase in death from all solid cancers.

Based on this, the authors estimated that 8% of solid cancer deaths, including 14% of breast cancer deaths, could be attributed to the radiation. When combined with current US mortality rates, that translated to around 13 excess solid cancer deaths, including three deaths from breast cancer, for every 1000 patients receiving a 100 mGy absorbed dose to the stomach or breast at age 40 years.

However they noted that patients with Graves disease are now recommended to receive higher doses, and calculated that for 150-mGy, 200-mGy and 250-mGy dosages there would be 19-32 excess solid cancer deaths per 1000 patients treated at age 40 years.

“To our knowledge, this is the first study to characterize the dose-response relationship between RAI treatment and site-specific cancer mortality in patients with hyperthyroidism using reliable estimates of absorbed dose to exposed organs or tissues,” wrote Cari M. Kitahara, PhD, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and co-authors.

Radioactive iodine therapy did not appear to be associated with an increased risk of death from leukemia, non-Hodgkin lymphoma or multiple myeloma.

The authors noted that this was unexpected given previous findings of an elevated risk of leukemia in patients with thyroid cancer who received higher levels of radiation. They suggested that the greater uncertainty in calculation of red bone marrow exposure compared to that of other organs and tissue, as well as the relatively small number of leukemia deaths, may have limited their ability to detect a dose-response relationship.

The study was funded by the National Cancer Institute. One author declared membership of a consortium supported by the pharmaceutical sector.
 

SOURCE: Kitahara C et al. JAMA Internal Medicine 2019, July 1. DOI:10.1001/jamainternmed.2019.0981.

Radioactive iodine therapy for hyperthyroidism may be associated with an increased risk of death from cancer, according to a longitudinal cohort study published in the July 1 issue of JAMA Internal Medicine.

Sebastian Kaulitzki/Fotolia

The study followed 18,805 individuals whose hyperthyroidism was treated with radioactive iodine in the United States and United Kingdom between 1946 and 1964.

Researchers found positive dose-response relationships between radioactive iodine therapy and most of the solid cancers that were evaluated. However these only attained statistical significance in the case of female breast cancer – where there was a 12% increase in the risk of death from breast cancer from a 100-mGy tissue- or organ-absorbed dose – or for all solid cancers combined, where a 100-mGy dose to the stomach was associated with a 6% increase in death from all solid cancers.

Based on this, the authors estimated that 8% of solid cancer deaths, including 14% of breast cancer deaths, could be attributed to the radiation. When combined with current US mortality rates, that translated to around 13 excess solid cancer deaths, including three deaths from breast cancer, for every 1000 patients receiving a 100 mGy absorbed dose to the stomach or breast at age 40 years.

However they noted that patients with Graves disease are now recommended to receive higher doses, and calculated that for 150-mGy, 200-mGy and 250-mGy dosages there would be 19-32 excess solid cancer deaths per 1000 patients treated at age 40 years.

“To our knowledge, this is the first study to characterize the dose-response relationship between RAI treatment and site-specific cancer mortality in patients with hyperthyroidism using reliable estimates of absorbed dose to exposed organs or tissues,” wrote Cari M. Kitahara, PhD, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and co-authors.

Radioactive iodine therapy did not appear to be associated with an increased risk of death from leukemia, non-Hodgkin lymphoma or multiple myeloma.

The authors noted that this was unexpected given previous findings of an elevated risk of leukemia in patients with thyroid cancer who received higher levels of radiation. They suggested that the greater uncertainty in calculation of red bone marrow exposure compared to that of other organs and tissue, as well as the relatively small number of leukemia deaths, may have limited their ability to detect a dose-response relationship.

The study was funded by the National Cancer Institute. One author declared membership of a consortium supported by the pharmaceutical sector.
 

SOURCE: Kitahara C et al. JAMA Internal Medicine 2019, July 1. DOI:10.1001/jamainternmed.2019.0981.

Radioactive iodine therapy for hyperthyroidism may be associated with an increased risk of death from cancer, according to a longitudinal cohort study published in the July 1 issue of JAMA Internal Medicine.

Sebastian Kaulitzki/Fotolia

The study followed 18,805 individuals whose hyperthyroidism was treated with radioactive iodine in the United States and United Kingdom between 1946 and 1964.

Researchers found positive dose-response relationships between radioactive iodine therapy and most of the solid cancers that were evaluated. However these only attained statistical significance in the case of female breast cancer – where there was a 12% increase in the risk of death from breast cancer from a 100-mGy tissue- or organ-absorbed dose – or for all solid cancers combined, where a 100-mGy dose to the stomach was associated with a 6% increase in death from all solid cancers.

Based on this, the authors estimated that 8% of solid cancer deaths, including 14% of breast cancer deaths, could be attributed to the radiation. When combined with current US mortality rates, that translated to around 13 excess solid cancer deaths, including three deaths from breast cancer, for every 1000 patients receiving a 100 mGy absorbed dose to the stomach or breast at age 40 years.

However they noted that patients with Graves disease are now recommended to receive higher doses, and calculated that for 150-mGy, 200-mGy and 250-mGy dosages there would be 19-32 excess solid cancer deaths per 1000 patients treated at age 40 years.

“To our knowledge, this is the first study to characterize the dose-response relationship between RAI treatment and site-specific cancer mortality in patients with hyperthyroidism using reliable estimates of absorbed dose to exposed organs or tissues,” wrote Cari M. Kitahara, PhD, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and co-authors.

Radioactive iodine therapy did not appear to be associated with an increased risk of death from leukemia, non-Hodgkin lymphoma or multiple myeloma.

The authors noted that this was unexpected given previous findings of an elevated risk of leukemia in patients with thyroid cancer who received higher levels of radiation. They suggested that the greater uncertainty in calculation of red bone marrow exposure compared to that of other organs and tissue, as well as the relatively small number of leukemia deaths, may have limited their ability to detect a dose-response relationship.

The study was funded by the National Cancer Institute. One author declared membership of a consortium supported by the pharmaceutical sector.
 

SOURCE: Kitahara C et al. JAMA Internal Medicine 2019, July 1. DOI:10.1001/jamainternmed.2019.0981.

Breast density should be a factor in assessing breast cancer risk and recommending supplemental imaging, but not the primary factor, according to a study of women who were screened for the disease.

Dr. Cecil Fox/National Cancer Institute

“Counseling strategies that identified women for supplemental imaging based on breast density and BCSC 5-year risk were more efficient compared with strategies based on age and density or density alone,” wrote Karla Kerlikowske, MD, of the Department of Veterans Affairs, and her coauthors. The study was published in JAMA Internal Medicine.

To assess breast cancer risk and strategies for recommending supplemental screening, the researchers assembled a cohort of 638,856 women aged 40 to 74 years who received mammograms at Breast Cancer Surveillance Consortium (BCSC) facilities from Jan. 3, 2005, to Dec. 31, 2014. Participants were identified as high risk via combinations of Breast Imaging Reporting and Data System (BI-RADS) breast density, BCSC 5-year breast cancer risk, and age.

Women with dense breasts made up 47% of those screened, and 60% of those with advanced cancers. Low advanced cancer rates (less than .61 per 1,000 mammograms) occurred in 34.5% of women with dense breasts, while high advanced cancer rates (greater than or equal to .61 cases per 1,000 mammograms) occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women).

In a hypothetical cohort of 100,000 women, supplemental imaging for all 47,012 women with dense breasts would mean a ratio of 1,866 supplemental imaging discussions per potential advanced breast cancer prevented. If imaging was considered based on a combination of density plus BCSC 5-year risk, the number of women screened would be reduced to 12,506 and the ratio would become 1,097 supplemental imaging discussions per potential advanced cancer prevented.

The coauthors acknowledged their study’s limitations, including their lack of ability to determine if women at high risk of advanced cancer would benefit from supplemental screening. In addition, they were unable to evaluate digital breast tomosynthesis outcomes, though they noted that, to their knowledge, “no published evidence indicates that advanced cancer rates differ for digital mammography vs. tomosynthesis according to breast density.”

The study was funded by the Patient-Centered Outcomes Research Institute, the Breast Cancer Surveillance Consortium, the National Cancer Institute, the Agency for Health Research and Quality, and the Lake Champlain Cancer Research Organization. The authors reported several potential conflicts of interest, including being members of various working groups, advisory boards, committees, task forces, and panels.

SOURCE: Kerlikowske K et al. JAMA Intern Med. 2019 Jul 1. doi:10.1001/jamainternmed.2019.1758 .

Breast density should be a factor in assessing breast cancer risk and recommending supplemental imaging, but not the primary factor, according to a study of women who were screened for the disease.

Dr. Cecil Fox/National Cancer Institute

“Counseling strategies that identified women for supplemental imaging based on breast density and BCSC 5-year risk were more efficient compared with strategies based on age and density or density alone,” wrote Karla Kerlikowske, MD, of the Department of Veterans Affairs, and her coauthors. The study was published in JAMA Internal Medicine.

To assess breast cancer risk and strategies for recommending supplemental screening, the researchers assembled a cohort of 638,856 women aged 40 to 74 years who received mammograms at Breast Cancer Surveillance Consortium (BCSC) facilities from Jan. 3, 2005, to Dec. 31, 2014. Participants were identified as high risk via combinations of Breast Imaging Reporting and Data System (BI-RADS) breast density, BCSC 5-year breast cancer risk, and age.

Women with dense breasts made up 47% of those screened, and 60% of those with advanced cancers. Low advanced cancer rates (less than .61 per 1,000 mammograms) occurred in 34.5% of women with dense breasts, while high advanced cancer rates (greater than or equal to .61 cases per 1,000 mammograms) occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women).

In a hypothetical cohort of 100,000 women, supplemental imaging for all 47,012 women with dense breasts would mean a ratio of 1,866 supplemental imaging discussions per potential advanced breast cancer prevented. If imaging was considered based on a combination of density plus BCSC 5-year risk, the number of women screened would be reduced to 12,506 and the ratio would become 1,097 supplemental imaging discussions per potential advanced cancer prevented.

The coauthors acknowledged their study’s limitations, including their lack of ability to determine if women at high risk of advanced cancer would benefit from supplemental screening. In addition, they were unable to evaluate digital breast tomosynthesis outcomes, though they noted that, to their knowledge, “no published evidence indicates that advanced cancer rates differ for digital mammography vs. tomosynthesis according to breast density.”

The study was funded by the Patient-Centered Outcomes Research Institute, the Breast Cancer Surveillance Consortium, the National Cancer Institute, the Agency for Health Research and Quality, and the Lake Champlain Cancer Research Organization. The authors reported several potential conflicts of interest, including being members of various working groups, advisory boards, committees, task forces, and panels.

SOURCE: Kerlikowske K et al. JAMA Intern Med. 2019 Jul 1. doi:10.1001/jamainternmed.2019.1758 .

Breast density should be a factor in assessing breast cancer risk and recommending supplemental imaging, but not the primary factor, according to a study of women who were screened for the disease.

Dr. Cecil Fox/National Cancer Institute

“Counseling strategies that identified women for supplemental imaging based on breast density and BCSC 5-year risk were more efficient compared with strategies based on age and density or density alone,” wrote Karla Kerlikowske, MD, of the Department of Veterans Affairs, and her coauthors. The study was published in JAMA Internal Medicine.

To assess breast cancer risk and strategies for recommending supplemental screening, the researchers assembled a cohort of 638,856 women aged 40 to 74 years who received mammograms at Breast Cancer Surveillance Consortium (BCSC) facilities from Jan. 3, 2005, to Dec. 31, 2014. Participants were identified as high risk via combinations of Breast Imaging Reporting and Data System (BI-RADS) breast density, BCSC 5-year breast cancer risk, and age.

Women with dense breasts made up 47% of those screened, and 60% of those with advanced cancers. Low advanced cancer rates (less than .61 per 1,000 mammograms) occurred in 34.5% of women with dense breasts, while high advanced cancer rates (greater than or equal to .61 cases per 1,000 mammograms) occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women).

In a hypothetical cohort of 100,000 women, supplemental imaging for all 47,012 women with dense breasts would mean a ratio of 1,866 supplemental imaging discussions per potential advanced breast cancer prevented. If imaging was considered based on a combination of density plus BCSC 5-year risk, the number of women screened would be reduced to 12,506 and the ratio would become 1,097 supplemental imaging discussions per potential advanced cancer prevented.

The coauthors acknowledged their study’s limitations, including their lack of ability to determine if women at high risk of advanced cancer would benefit from supplemental screening. In addition, they were unable to evaluate digital breast tomosynthesis outcomes, though they noted that, to their knowledge, “no published evidence indicates that advanced cancer rates differ for digital mammography vs. tomosynthesis according to breast density.”

The study was funded by the Patient-Centered Outcomes Research Institute, the Breast Cancer Surveillance Consortium, the National Cancer Institute, the Agency for Health Research and Quality, and the Lake Champlain Cancer Research Organization. The authors reported several potential conflicts of interest, including being members of various working groups, advisory boards, committees, task forces, and panels.

SOURCE: Kerlikowske K et al. JAMA Intern Med. 2019 Jul 1. doi:10.1001/jamainternmed.2019.1758 .

SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office). Talk about smartphone alarms, promote auto-fill services, and understand why patients don’t adhere to their regimens.

Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.

“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”

According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).

Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).

Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.

Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).

Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:

• Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
• Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
• Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
• Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
• Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
• Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.

And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.

Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.

SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office). Talk about smartphone alarms, promote auto-fill services, and understand why patients don’t adhere to their regimens.

Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.

“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”

According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).

Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).

Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.

Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).

Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:

• Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
• Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
• Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
• Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
• Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
• Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.

And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.

Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.

SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office). Talk about smartphone alarms, promote auto-fill services, and understand why patients don’t adhere to their regimens.

Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.

“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”

According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).

Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).

Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.

Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).

Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:

• Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
• Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
• Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
• Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
• Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
• Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.

And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.

Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.