LONDON – Maintenance azithromycin may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) who also have few symptoms, according to an analysis from the COLUMBUS randomized controlled trial.

Significantly fewer exacerbations (1.06 vs. 2.62; P = .02) occurred at 1 year in patients treated with the macrolide antibiotic azithromycin rather than placebo if they were classified as having GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 1 or 2 versus stage 4.

©decade3d/Thinkstock

Study participants who were classified as being part of GOLD group C (which includes patients with a high risk of COPD exacerbation but a low level of COPD symptoms) who were treated with maintenance azithromycin were also more likely to have fewer exacerbations at 1 year, compared with patients classified as being part of GOLD group D (which includes patients with a high risk of COPD exacerbation and a high level of COPD symptoms), who took the same antibiotic (0.45 vs. 2.18; P less than .01).

Having a high serum eosinophil level (2% or higher) was a third factor found in COPD patients that was predictive of fewer exacerbations following azithromycin use (1.26 vs. 2.5; P = .02).

“Azithromycin maintenance therapy should not be given to every COPD patient,” Remco Djamin, MD, of Amphia Hospital Breda in the Netherlands said in an interview at the annual congress of the European Respiratory Society. There is, of course, the concern over antibiotic resistance developing and macrolide antibiotic use has been linked with heart problems such as arrhythmia.

These data show, however, that there are certain predictors that might help clinicians decide if long-term antibiotic therapy might be beneficial for their patients who are experiencing frequent acute exacerbations of COPD.

Further research should look at the dosing and duration of azithromycin, Dr. Djamin suggested. Perhaps reducing the dose by half to 250 mg three times per week would be just as good; maybe 6 months’ rather than 12 months’ treatment would be sufficient, or perhaps it could be given intermittently. The aim is to ensure that patients are not being exposed unnecessarily, as there is concern over antibiotic resistance.

The use of azithromycin is not currently recommended in guidelines for COPD management to prevent exacerbations, but it is something that is likely to be added to the guidelines, as the evidence for its benefit mounts, Dr. Djamin said.

In addition to COLUMBUS, there have been at least two other studies looking at long-term antibiotic use to prevent exacerbations in patients with COPD. One (Am J Respir Crit Care Med. 2008;178:1139-47) showed erythromycin could decrease the exacerbation rate at 1 year by 36%, compared with placebo, while the other (N Engl J Med. 2011;365:689-8) again showed a benefit for azithromycin, with a 27% decrease in the 1-year exacerbation rate.

In COLUMBUS, 92 patients who had experienced at least three or more acute COPD exacerbations in the previous year were randomized to treatment with azithromycin 500 mg or placebo, taken three times per week for 12 months. This was a single-center, double-blind trial conducted in the Netherlands that showed a 42% reduction in the 1-year exacerbation rate could be achieved with the antibiotic treatment (Lancet Respir Med. 2014;2:361-8).

An additional benefit to using the antibiotic was seen in patients with GOLD stage 1-2 over patients with GOLD stage 4 and in patients with a higher percentage of serum eosinophils. The GOLD stage 1-2 patients experienced fewer exacerbations leading to hospitalization, compared with patients with GOLD stage 4 (0.31 vs. 1.00; P = .04), while the patients with higher levels of eosinophils experienced fewer exacerbations requiring hospitalization than those patients with lower percentages of eosinophils (0.26 vs. 1.07; P = 0.01).

“What you should consider is that this is a group of patients who have frequent exacerbations, and most of these exacerbations are caused by infections,” Dr. Djamin said, during a poster presentation at the conference. “Their exacerbations are often already being treated with antibiotics and so maintaining treatment has become one possible way of perhaps preventing exacerbations in the future.”

The study received no industry funding. Dr. Djamin had no competing interests to disclose.

LONDON – Maintenance azithromycin may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) who also have few symptoms, according to an analysis from the COLUMBUS randomized controlled trial.

Significantly fewer exacerbations (1.06 vs. 2.62; P = .02) occurred at 1 year in patients treated with the macrolide antibiotic azithromycin rather than placebo if they were classified as having GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 1 or 2 versus stage 4.

©decade3d/Thinkstock

Study participants who were classified as being part of GOLD group C (which includes patients with a high risk of COPD exacerbation but a low level of COPD symptoms) who were treated with maintenance azithromycin were also more likely to have fewer exacerbations at 1 year, compared with patients classified as being part of GOLD group D (which includes patients with a high risk of COPD exacerbation and a high level of COPD symptoms), who took the same antibiotic (0.45 vs. 2.18; P less than .01).

Having a high serum eosinophil level (2% or higher) was a third factor found in COPD patients that was predictive of fewer exacerbations following azithromycin use (1.26 vs. 2.5; P = .02).

“Azithromycin maintenance therapy should not be given to every COPD patient,” Remco Djamin, MD, of Amphia Hospital Breda in the Netherlands said in an interview at the annual congress of the European Respiratory Society. There is, of course, the concern over antibiotic resistance developing and macrolide antibiotic use has been linked with heart problems such as arrhythmia.

These data show, however, that there are certain predictors that might help clinicians decide if long-term antibiotic therapy might be beneficial for their patients who are experiencing frequent acute exacerbations of COPD.

Further research should look at the dosing and duration of azithromycin, Dr. Djamin suggested. Perhaps reducing the dose by half to 250 mg three times per week would be just as good; maybe 6 months’ rather than 12 months’ treatment would be sufficient, or perhaps it could be given intermittently. The aim is to ensure that patients are not being exposed unnecessarily, as there is concern over antibiotic resistance.

The use of azithromycin is not currently recommended in guidelines for COPD management to prevent exacerbations, but it is something that is likely to be added to the guidelines, as the evidence for its benefit mounts, Dr. Djamin said.

In addition to COLUMBUS, there have been at least two other studies looking at long-term antibiotic use to prevent exacerbations in patients with COPD. One (Am J Respir Crit Care Med. 2008;178:1139-47) showed erythromycin could decrease the exacerbation rate at 1 year by 36%, compared with placebo, while the other (N Engl J Med. 2011;365:689-8) again showed a benefit for azithromycin, with a 27% decrease in the 1-year exacerbation rate.

In COLUMBUS, 92 patients who had experienced at least three or more acute COPD exacerbations in the previous year were randomized to treatment with azithromycin 500 mg or placebo, taken three times per week for 12 months. This was a single-center, double-blind trial conducted in the Netherlands that showed a 42% reduction in the 1-year exacerbation rate could be achieved with the antibiotic treatment (Lancet Respir Med. 2014;2:361-8).

An additional benefit to using the antibiotic was seen in patients with GOLD stage 1-2 over patients with GOLD stage 4 and in patients with a higher percentage of serum eosinophils. The GOLD stage 1-2 patients experienced fewer exacerbations leading to hospitalization, compared with patients with GOLD stage 4 (0.31 vs. 1.00; P = .04), while the patients with higher levels of eosinophils experienced fewer exacerbations requiring hospitalization than those patients with lower percentages of eosinophils (0.26 vs. 1.07; P = 0.01).

“What you should consider is that this is a group of patients who have frequent exacerbations, and most of these exacerbations are caused by infections,” Dr. Djamin said, during a poster presentation at the conference. “Their exacerbations are often already being treated with antibiotics and so maintaining treatment has become one possible way of perhaps preventing exacerbations in the future.”

The study received no industry funding. Dr. Djamin had no competing interests to disclose.

LONDON – Maintenance azithromycin may be best reserved for patients with mild to moderate chronic obstructive pulmonary disease (COPD) who also have few symptoms, according to an analysis from the COLUMBUS randomized controlled trial.

Significantly fewer exacerbations (1.06 vs. 2.62; P = .02) occurred at 1 year in patients treated with the macrolide antibiotic azithromycin rather than placebo if they were classified as having GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 1 or 2 versus stage 4.

©decade3d/Thinkstock

Study participants who were classified as being part of GOLD group C (which includes patients with a high risk of COPD exacerbation but a low level of COPD symptoms) who were treated with maintenance azithromycin were also more likely to have fewer exacerbations at 1 year, compared with patients classified as being part of GOLD group D (which includes patients with a high risk of COPD exacerbation and a high level of COPD symptoms), who took the same antibiotic (0.45 vs. 2.18; P less than .01).

Having a high serum eosinophil level (2% or higher) was a third factor found in COPD patients that was predictive of fewer exacerbations following azithromycin use (1.26 vs. 2.5; P = .02).

“Azithromycin maintenance therapy should not be given to every COPD patient,” Remco Djamin, MD, of Amphia Hospital Breda in the Netherlands said in an interview at the annual congress of the European Respiratory Society. There is, of course, the concern over antibiotic resistance developing and macrolide antibiotic use has been linked with heart problems such as arrhythmia.

These data show, however, that there are certain predictors that might help clinicians decide if long-term antibiotic therapy might be beneficial for their patients who are experiencing frequent acute exacerbations of COPD.

Further research should look at the dosing and duration of azithromycin, Dr. Djamin suggested. Perhaps reducing the dose by half to 250 mg three times per week would be just as good; maybe 6 months’ rather than 12 months’ treatment would be sufficient, or perhaps it could be given intermittently. The aim is to ensure that patients are not being exposed unnecessarily, as there is concern over antibiotic resistance.

The use of azithromycin is not currently recommended in guidelines for COPD management to prevent exacerbations, but it is something that is likely to be added to the guidelines, as the evidence for its benefit mounts, Dr. Djamin said.

In addition to COLUMBUS, there have been at least two other studies looking at long-term antibiotic use to prevent exacerbations in patients with COPD. One (Am J Respir Crit Care Med. 2008;178:1139-47) showed erythromycin could decrease the exacerbation rate at 1 year by 36%, compared with placebo, while the other (N Engl J Med. 2011;365:689-8) again showed a benefit for azithromycin, with a 27% decrease in the 1-year exacerbation rate.

In COLUMBUS, 92 patients who had experienced at least three or more acute COPD exacerbations in the previous year were randomized to treatment with azithromycin 500 mg or placebo, taken three times per week for 12 months. This was a single-center, double-blind trial conducted in the Netherlands that showed a 42% reduction in the 1-year exacerbation rate could be achieved with the antibiotic treatment (Lancet Respir Med. 2014;2:361-8).

An additional benefit to using the antibiotic was seen in patients with GOLD stage 1-2 over patients with GOLD stage 4 and in patients with a higher percentage of serum eosinophils. The GOLD stage 1-2 patients experienced fewer exacerbations leading to hospitalization, compared with patients with GOLD stage 4 (0.31 vs. 1.00; P = .04), while the patients with higher levels of eosinophils experienced fewer exacerbations requiring hospitalization than those patients with lower percentages of eosinophils (0.26 vs. 1.07; P = 0.01).

“What you should consider is that this is a group of patients who have frequent exacerbations, and most of these exacerbations are caused by infections,” Dr. Djamin said, during a poster presentation at the conference. “Their exacerbations are often already being treated with antibiotics and so maintaining treatment has become one possible way of perhaps preventing exacerbations in the future.”

The study received no industry funding. Dr. Djamin had no competing interests to disclose.

The porcine acellular dermal mesh product Strattice was associated with significantly lower odds of hernia recurrence, compared with several other biologic mesh products, in a study of 223 patients who underwent open ventral hernia repair.

Prospective operative outcomes data from a tertiary referral hernia center showed that at a mean follow-up of 18.2 months, the rate of hernia recurrence was 35% in 40 patients who were treated with Alloderm (LifeCell Corporation), 34.5% in 23 patients treated with AlloMax (Bard/Davol), 37.1% in 70 patients treated with FlexHD (Ethicon), and 59.1% in 22 patients treated with Xenmatrix (Bard/Davol), compared with 14.7% in 68 patients treated with Strattice (LifeCell Corporation). Alloderm, AlloMax, and FlexHD are all human acellular dermal mesh products, and Strattice and Xenmatrix are both porcine acellular dermal mesh products, Ciara R. Huntington, MD, and her colleagues at the Carolinas Medical Center in Charlotte, N.C., reported.

Photo courtesy Acelity. STRATTICETM Reconstructive Tissue Matrix

After multivariate analysis to adjust for factors such as comorbidities, hernia size, and intraoperative techniques, the odds ratios for recurrence with each product as compared with Strattice were 2.4 with Alloderm, 2.9 with FlexHD, 3.4 with AlloMax, and 7.8 with Xenmatrix. The odds for recurrence were significantly greater with all except Alloderm, the investigators said (Surgery. 2016. doi: 10.1016/j.surg.2016.07.008).

The significant differences between the two porcine acellular dermal meshes (Xenmatrix and Strattice) may reflect variation in tissue processing and design in biomesh engineering, they noted.

Study subjects were adults with a mean age of 57.7 years and mean body mass index of 34.8 kg/m². Overall, 9.8% had an American Society of Anesthesiology classification of 4, 54.6% had a classification of 3, and 35.6% had a classification of 1 or 2. Average operative time was 241 minutes with estimated blood loss of 202 mL.

Average hernia defect size was 257 cm², with average mesh size of 384 cm².

“Component separation was performed in 47.5% of cases, and abdomen was left open prior to definitive closure in 10.7%. Biologic mesh was used to bridge fascial defects in 19.6% of cases. The mesh was placed in the preperitoneal space in 38.2% of cases,” the investigators wrote, noting that a concomitant procedure was performed in 82% of cases.

Sepsis developed in 6.7% of patients, 36.3% had a wound infection, and 24.3% required a negative pressure dressing for healing. The inpatient mortality rate was 1.4%.

However, mesh infections requiring explantation occurred in less than 1% of cases.

On adjusted analysis, Xenmatrix was the most expensive mesh and AlloMax was the least expensive (mean of $59,122 and $22,304, respectively). Strattice costs averaged $40,490.

Ventral hernia repair (VHR) is a common operation, with about 350,000 performed each year. Rates of postoperative wound infection and hernia recurrence vary widely, but may be improved with appropriate mesh selection. However, prospective data to guide selection are lacking, the investigators said.

“The great number of meshes available for use complicates the debate surrounding the best timing and use of biologic mesh in VHR, and the search for the better mesh for use in the abdominal wall reconstruction continues. Biologic mesh usually is reserved for the patients at the highest risk for developing a postoperative wound complication, and although there is a current dearth of high-level evidence supporting its use, this report confirms that complications are low despite obvious surgical complexity presented herein,” they wrote.

The findings of this study – the largest report of outcomes with biologic mesh in ventral hernia repair to date, according to the authors – support the safety of using biologic mesh in high-risk patients, they said.

They noted, however, that the study may still be underpowered to make final clinical decisions.

“Although our study provides useful information to the practicing surgeon, there is much work to be done regarding the selection of biologic mesh,” they wrote, adding that while “a well-performing biologic mesh should be in the toolkit of every general surgeon who may face complex abdominal walls requiring reconstruction in patients that are at high risk for a postoperative wound complication,” additional research is necessary to further clarify the role of biologic mesh in these operations.

Dr. Huntington reported having no disclosures. Other authors reported having been awarded honoraria, speaking fees, surgical research funding, and education grants from W.L. Gore and Associates, Ethicon, Novadaq, Bard/Davol, and LifeCell Corporation.

sworcester@frontlinemedcom.com

The porcine acellular dermal mesh product Strattice was associated with significantly lower odds of hernia recurrence, compared with several other biologic mesh products, in a study of 223 patients who underwent open ventral hernia repair.

Prospective operative outcomes data from a tertiary referral hernia center showed that at a mean follow-up of 18.2 months, the rate of hernia recurrence was 35% in 40 patients who were treated with Alloderm (LifeCell Corporation), 34.5% in 23 patients treated with AlloMax (Bard/Davol), 37.1% in 70 patients treated with FlexHD (Ethicon), and 59.1% in 22 patients treated with Xenmatrix (Bard/Davol), compared with 14.7% in 68 patients treated with Strattice (LifeCell Corporation). Alloderm, AlloMax, and FlexHD are all human acellular dermal mesh products, and Strattice and Xenmatrix are both porcine acellular dermal mesh products, Ciara R. Huntington, MD, and her colleagues at the Carolinas Medical Center in Charlotte, N.C., reported.

Photo courtesy Acelity. STRATTICETM Reconstructive Tissue Matrix

After multivariate analysis to adjust for factors such as comorbidities, hernia size, and intraoperative techniques, the odds ratios for recurrence with each product as compared with Strattice were 2.4 with Alloderm, 2.9 with FlexHD, 3.4 with AlloMax, and 7.8 with Xenmatrix. The odds for recurrence were significantly greater with all except Alloderm, the investigators said (Surgery. 2016. doi: 10.1016/j.surg.2016.07.008).

The significant differences between the two porcine acellular dermal meshes (Xenmatrix and Strattice) may reflect variation in tissue processing and design in biomesh engineering, they noted.

Study subjects were adults with a mean age of 57.7 years and mean body mass index of 34.8 kg/m². Overall, 9.8% had an American Society of Anesthesiology classification of 4, 54.6% had a classification of 3, and 35.6% had a classification of 1 or 2. Average operative time was 241 minutes with estimated blood loss of 202 mL.

Average hernia defect size was 257 cm², with average mesh size of 384 cm².

“Component separation was performed in 47.5% of cases, and abdomen was left open prior to definitive closure in 10.7%. Biologic mesh was used to bridge fascial defects in 19.6% of cases. The mesh was placed in the preperitoneal space in 38.2% of cases,” the investigators wrote, noting that a concomitant procedure was performed in 82% of cases.

Sepsis developed in 6.7% of patients, 36.3% had a wound infection, and 24.3% required a negative pressure dressing for healing. The inpatient mortality rate was 1.4%.

However, mesh infections requiring explantation occurred in less than 1% of cases.

On adjusted analysis, Xenmatrix was the most expensive mesh and AlloMax was the least expensive (mean of $59,122 and $22,304, respectively). Strattice costs averaged $40,490.

Ventral hernia repair (VHR) is a common operation, with about 350,000 performed each year. Rates of postoperative wound infection and hernia recurrence vary widely, but may be improved with appropriate mesh selection. However, prospective data to guide selection are lacking, the investigators said.

“The great number of meshes available for use complicates the debate surrounding the best timing and use of biologic mesh in VHR, and the search for the better mesh for use in the abdominal wall reconstruction continues. Biologic mesh usually is reserved for the patients at the highest risk for developing a postoperative wound complication, and although there is a current dearth of high-level evidence supporting its use, this report confirms that complications are low despite obvious surgical complexity presented herein,” they wrote.

The findings of this study – the largest report of outcomes with biologic mesh in ventral hernia repair to date, according to the authors – support the safety of using biologic mesh in high-risk patients, they said.

They noted, however, that the study may still be underpowered to make final clinical decisions.

“Although our study provides useful information to the practicing surgeon, there is much work to be done regarding the selection of biologic mesh,” they wrote, adding that while “a well-performing biologic mesh should be in the toolkit of every general surgeon who may face complex abdominal walls requiring reconstruction in patients that are at high risk for a postoperative wound complication,” additional research is necessary to further clarify the role of biologic mesh in these operations.

Dr. Huntington reported having no disclosures. Other authors reported having been awarded honoraria, speaking fees, surgical research funding, and education grants from W.L. Gore and Associates, Ethicon, Novadaq, Bard/Davol, and LifeCell Corporation.

sworcester@frontlinemedcom.com

The porcine acellular dermal mesh product Strattice was associated with significantly lower odds of hernia recurrence, compared with several other biologic mesh products, in a study of 223 patients who underwent open ventral hernia repair.

Prospective operative outcomes data from a tertiary referral hernia center showed that at a mean follow-up of 18.2 months, the rate of hernia recurrence was 35% in 40 patients who were treated with Alloderm (LifeCell Corporation), 34.5% in 23 patients treated with AlloMax (Bard/Davol), 37.1% in 70 patients treated with FlexHD (Ethicon), and 59.1% in 22 patients treated with Xenmatrix (Bard/Davol), compared with 14.7% in 68 patients treated with Strattice (LifeCell Corporation). Alloderm, AlloMax, and FlexHD are all human acellular dermal mesh products, and Strattice and Xenmatrix are both porcine acellular dermal mesh products, Ciara R. Huntington, MD, and her colleagues at the Carolinas Medical Center in Charlotte, N.C., reported.

Photo courtesy Acelity. STRATTICETM Reconstructive Tissue Matrix

After multivariate analysis to adjust for factors such as comorbidities, hernia size, and intraoperative techniques, the odds ratios for recurrence with each product as compared with Strattice were 2.4 with Alloderm, 2.9 with FlexHD, 3.4 with AlloMax, and 7.8 with Xenmatrix. The odds for recurrence were significantly greater with all except Alloderm, the investigators said (Surgery. 2016. doi: 10.1016/j.surg.2016.07.008).

The significant differences between the two porcine acellular dermal meshes (Xenmatrix and Strattice) may reflect variation in tissue processing and design in biomesh engineering, they noted.

Study subjects were adults with a mean age of 57.7 years and mean body mass index of 34.8 kg/m². Overall, 9.8% had an American Society of Anesthesiology classification of 4, 54.6% had a classification of 3, and 35.6% had a classification of 1 or 2. Average operative time was 241 minutes with estimated blood loss of 202 mL.

Average hernia defect size was 257 cm², with average mesh size of 384 cm².

“Component separation was performed in 47.5% of cases, and abdomen was left open prior to definitive closure in 10.7%. Biologic mesh was used to bridge fascial defects in 19.6% of cases. The mesh was placed in the preperitoneal space in 38.2% of cases,” the investigators wrote, noting that a concomitant procedure was performed in 82% of cases.

Sepsis developed in 6.7% of patients, 36.3% had a wound infection, and 24.3% required a negative pressure dressing for healing. The inpatient mortality rate was 1.4%.

However, mesh infections requiring explantation occurred in less than 1% of cases.

On adjusted analysis, Xenmatrix was the most expensive mesh and AlloMax was the least expensive (mean of $59,122 and $22,304, respectively). Strattice costs averaged $40,490.

Ventral hernia repair (VHR) is a common operation, with about 350,000 performed each year. Rates of postoperative wound infection and hernia recurrence vary widely, but may be improved with appropriate mesh selection. However, prospective data to guide selection are lacking, the investigators said.

“The great number of meshes available for use complicates the debate surrounding the best timing and use of biologic mesh in VHR, and the search for the better mesh for use in the abdominal wall reconstruction continues. Biologic mesh usually is reserved for the patients at the highest risk for developing a postoperative wound complication, and although there is a current dearth of high-level evidence supporting its use, this report confirms that complications are low despite obvious surgical complexity presented herein,” they wrote.

The findings of this study – the largest report of outcomes with biologic mesh in ventral hernia repair to date, according to the authors – support the safety of using biologic mesh in high-risk patients, they said.

They noted, however, that the study may still be underpowered to make final clinical decisions.

“Although our study provides useful information to the practicing surgeon, there is much work to be done regarding the selection of biologic mesh,” they wrote, adding that while “a well-performing biologic mesh should be in the toolkit of every general surgeon who may face complex abdominal walls requiring reconstruction in patients that are at high risk for a postoperative wound complication,” additional research is necessary to further clarify the role of biologic mesh in these operations.

Dr. Huntington reported having no disclosures. Other authors reported having been awarded honoraria, speaking fees, surgical research funding, and education grants from W.L. Gore and Associates, Ethicon, Novadaq, Bard/Davol, and LifeCell Corporation.

sworcester@frontlinemedcom.com

An international study “unprecedented in both scale and scope” has provided some important answers to the mysteries of how diabetes develops—not least, the answer to a century-old debate about whether genetic differences are shared and common or rare and individual.

Led by researchers from University of Michigan, University of Oxford, Massachusetts Institute of Technology (MIT), Harvard University, and Massachusetts General Hospital, more than 300 scientists from 22 countries used DNA from 120,000 individuals to pinpoint genes and their variants.

Related: A Window Into the Genetics Behind Diabetes

The collaboration brought together 2 research projects: GoT2D and T2D-DENES. The research teams completed whole genome sequencing of more than 2,600 people and exome sequencing of 12,940, as well as genome- or exomewide array genotyping of 111,548 people. Unlike most previous studies, which involved people only of European ancestry, this study included people with ancestral origins in Europe, South and East Asia, the Americas, and Africa.

The researchers were able to highlight “with unprecedented precision” a number of genes directly involved in the development of type 2 diabetes mellitus (T2DM)—promising new avenues for research into treatment or prevention. They also identified more than a dozen genetic regions that harbor variants that influence risk of T2DM. Most were common to all human populations and had previously been detected by other genomewide association studies.

Related: Confronting the Diabetes Epidemic

“While rare variants certainly influence type 2 diabetes risk, our results demonstrate that common variants shared across populations explain most of the genetic risk,” said Michael Boehnke, director of the Center for Statistical Genetics at the University of Michigan School of Public Health and one of the study’s  3 senior authors.

“The conclusions seem clear,” agreed Mark McCarthy, Group Head, Wellcome Trust Centre for Human Genetics. He noted, “[T]he evidence is increasingly stacking up in favor of the view that most of the genetic risk of T2D can be attributed to common alleles that are widely shared within, and between, human populations.”

Related: Thanks to IHS Funding Program, “Sustained Achievements” in Diabetes Prevention

“While this large range of genetic risk may challenge our efforts at precision medicine,” said Jason Flannick, co-lead author and senior group leader at the Broad Institute of Harvard and MIT and research associate at the Massachusetts General Hospital, “our consortium also offers a publicly accessible dataset, unprecedented in scope, for researchers around the world to advance our molecular understanding of type 2 diabetes.”

An international study “unprecedented in both scale and scope” has provided some important answers to the mysteries of how diabetes develops—not least, the answer to a century-old debate about whether genetic differences are shared and common or rare and individual.

Led by researchers from University of Michigan, University of Oxford, Massachusetts Institute of Technology (MIT), Harvard University, and Massachusetts General Hospital, more than 300 scientists from 22 countries used DNA from 120,000 individuals to pinpoint genes and their variants.

Related: A Window Into the Genetics Behind Diabetes

The collaboration brought together 2 research projects: GoT2D and T2D-DENES. The research teams completed whole genome sequencing of more than 2,600 people and exome sequencing of 12,940, as well as genome- or exomewide array genotyping of 111,548 people. Unlike most previous studies, which involved people only of European ancestry, this study included people with ancestral origins in Europe, South and East Asia, the Americas, and Africa.

The researchers were able to highlight “with unprecedented precision” a number of genes directly involved in the development of type 2 diabetes mellitus (T2DM)—promising new avenues for research into treatment or prevention. They also identified more than a dozen genetic regions that harbor variants that influence risk of T2DM. Most were common to all human populations and had previously been detected by other genomewide association studies.

Related: Confronting the Diabetes Epidemic

“While rare variants certainly influence type 2 diabetes risk, our results demonstrate that common variants shared across populations explain most of the genetic risk,” said Michael Boehnke, director of the Center for Statistical Genetics at the University of Michigan School of Public Health and one of the study’s  3 senior authors.

“The conclusions seem clear,” agreed Mark McCarthy, Group Head, Wellcome Trust Centre for Human Genetics. He noted, “[T]he evidence is increasingly stacking up in favor of the view that most of the genetic risk of T2D can be attributed to common alleles that are widely shared within, and between, human populations.”

Related: Thanks to IHS Funding Program, “Sustained Achievements” in Diabetes Prevention

“While this large range of genetic risk may challenge our efforts at precision medicine,” said Jason Flannick, co-lead author and senior group leader at the Broad Institute of Harvard and MIT and research associate at the Massachusetts General Hospital, “our consortium also offers a publicly accessible dataset, unprecedented in scope, for researchers around the world to advance our molecular understanding of type 2 diabetes.”

An international study “unprecedented in both scale and scope” has provided some important answers to the mysteries of how diabetes develops—not least, the answer to a century-old debate about whether genetic differences are shared and common or rare and individual.

Led by researchers from University of Michigan, University of Oxford, Massachusetts Institute of Technology (MIT), Harvard University, and Massachusetts General Hospital, more than 300 scientists from 22 countries used DNA from 120,000 individuals to pinpoint genes and their variants.

Related: A Window Into the Genetics Behind Diabetes

The collaboration brought together 2 research projects: GoT2D and T2D-DENES. The research teams completed whole genome sequencing of more than 2,600 people and exome sequencing of 12,940, as well as genome- or exomewide array genotyping of 111,548 people. Unlike most previous studies, which involved people only of European ancestry, this study included people with ancestral origins in Europe, South and East Asia, the Americas, and Africa.

The researchers were able to highlight “with unprecedented precision” a number of genes directly involved in the development of type 2 diabetes mellitus (T2DM)—promising new avenues for research into treatment or prevention. They also identified more than a dozen genetic regions that harbor variants that influence risk of T2DM. Most were common to all human populations and had previously been detected by other genomewide association studies.

Related: Confronting the Diabetes Epidemic

“While rare variants certainly influence type 2 diabetes risk, our results demonstrate that common variants shared across populations explain most of the genetic risk,” said Michael Boehnke, director of the Center for Statistical Genetics at the University of Michigan School of Public Health and one of the study’s  3 senior authors.

“The conclusions seem clear,” agreed Mark McCarthy, Group Head, Wellcome Trust Centre for Human Genetics. He noted, “[T]he evidence is increasingly stacking up in favor of the view that most of the genetic risk of T2D can be attributed to common alleles that are widely shared within, and between, human populations.”

Related: Thanks to IHS Funding Program, “Sustained Achievements” in Diabetes Prevention

“While this large range of genetic risk may challenge our efforts at precision medicine,” said Jason Flannick, co-lead author and senior group leader at the Broad Institute of Harvard and MIT and research associate at the Massachusetts General Hospital, “our consortium also offers a publicly accessible dataset, unprecedented in scope, for researchers around the world to advance our molecular understanding of type 2 diabetes.”

Micrograph showing AML

Compounds that inhibit the metabolic enzyme dihydroorotate dehydrogenase (DHODH) may be effective in treating acute myeloid leukemia (AML), according to preclinical research.

Investigators found that inhibiting DHODH enables myeloid differentiation in AML cells.

In mouse models of AML, treatment with a DHODH inhibitor reduced leukemia burden, decreased leukemia-initiating cell activity, and improved survival.

David Scadden, MD, of Massachusetts General Hospital in Boston, and his colleagues conducted this research and reported the results in Cell.

The research began with the observation that HoxA9, which is normally downregulated during myeloid differentiation, is expressed in roughly 70% of AML patients.

Since no inhibitors of HoxA9 have been identified, Dr Scadden and his colleagues set out to identify compounds that could overcome the differentiation blockade characteristic of AML cells.

The investigators first set up a cellular model of AML by inducing HoxA9 overexpression in mouse myeloid cells genetically engineered to fluoresce if they reached maturity.

The team then screened more than 330,000 small molecules, looking for those that would cause the cells to fluoresce, indicating that the HoxA9-induced differentiation blockade had been overcome.

Only 12 compounds produced the desired result. Eleven of these compounds were found to act by suppressing DHODH, which was not previously known to have a role in myeloid differentiation.

Further experiments showed that DHODH inhibition could induce differentiation in both mouse and human AML cells.

The investigators then tested BRQ, a known DHODH inhibitor, in several mouse models of AML.

Treatment with BRQ led to differentiation, reduced leukemia burden, decreased activity of leukemia-initiating cells, and prolonged survival when compared to treatment with cytarabine and doxorubicin.

“Drug companies tend to be skeptical of the kind of functional screening we used to identify DHODH as a target because it can be complicated and imprecise,” Dr Scadden noted.

“We think that, with modern tools, we may be able to improve target identification, so applying this approach to a broader range of cancers may be justified.”

Micrograph showing AML

Compounds that inhibit the metabolic enzyme dihydroorotate dehydrogenase (DHODH) may be effective in treating acute myeloid leukemia (AML), according to preclinical research.

Investigators found that inhibiting DHODH enables myeloid differentiation in AML cells.

In mouse models of AML, treatment with a DHODH inhibitor reduced leukemia burden, decreased leukemia-initiating cell activity, and improved survival.

David Scadden, MD, of Massachusetts General Hospital in Boston, and his colleagues conducted this research and reported the results in Cell.

The research began with the observation that HoxA9, which is normally downregulated during myeloid differentiation, is expressed in roughly 70% of AML patients.

Since no inhibitors of HoxA9 have been identified, Dr Scadden and his colleagues set out to identify compounds that could overcome the differentiation blockade characteristic of AML cells.

The investigators first set up a cellular model of AML by inducing HoxA9 overexpression in mouse myeloid cells genetically engineered to fluoresce if they reached maturity.

The team then screened more than 330,000 small molecules, looking for those that would cause the cells to fluoresce, indicating that the HoxA9-induced differentiation blockade had been overcome.

Only 12 compounds produced the desired result. Eleven of these compounds were found to act by suppressing DHODH, which was not previously known to have a role in myeloid differentiation.

Further experiments showed that DHODH inhibition could induce differentiation in both mouse and human AML cells.

The investigators then tested BRQ, a known DHODH inhibitor, in several mouse models of AML.

Treatment with BRQ led to differentiation, reduced leukemia burden, decreased activity of leukemia-initiating cells, and prolonged survival when compared to treatment with cytarabine and doxorubicin.

“Drug companies tend to be skeptical of the kind of functional screening we used to identify DHODH as a target because it can be complicated and imprecise,” Dr Scadden noted.

“We think that, with modern tools, we may be able to improve target identification, so applying this approach to a broader range of cancers may be justified.”

Micrograph showing AML

Compounds that inhibit the metabolic enzyme dihydroorotate dehydrogenase (DHODH) may be effective in treating acute myeloid leukemia (AML), according to preclinical research.

Investigators found that inhibiting DHODH enables myeloid differentiation in AML cells.

In mouse models of AML, treatment with a DHODH inhibitor reduced leukemia burden, decreased leukemia-initiating cell activity, and improved survival.

David Scadden, MD, of Massachusetts General Hospital in Boston, and his colleagues conducted this research and reported the results in Cell.

The research began with the observation that HoxA9, which is normally downregulated during myeloid differentiation, is expressed in roughly 70% of AML patients.

Since no inhibitors of HoxA9 have been identified, Dr Scadden and his colleagues set out to identify compounds that could overcome the differentiation blockade characteristic of AML cells.

The investigators first set up a cellular model of AML by inducing HoxA9 overexpression in mouse myeloid cells genetically engineered to fluoresce if they reached maturity.

The team then screened more than 330,000 small molecules, looking for those that would cause the cells to fluoresce, indicating that the HoxA9-induced differentiation blockade had been overcome.

Only 12 compounds produced the desired result. Eleven of these compounds were found to act by suppressing DHODH, which was not previously known to have a role in myeloid differentiation.

Further experiments showed that DHODH inhibition could induce differentiation in both mouse and human AML cells.

The investigators then tested BRQ, a known DHODH inhibitor, in several mouse models of AML.

Treatment with BRQ led to differentiation, reduced leukemia burden, decreased activity of leukemia-initiating cells, and prolonged survival when compared to treatment with cytarabine and doxorubicin.

“Drug companies tend to be skeptical of the kind of functional screening we used to identify DHODH as a target because it can be complicated and imprecise,” Dr Scadden noted.

“We think that, with modern tools, we may be able to improve target identification, so applying this approach to a broader range of cancers may be justified.”

Blood samples

Photo by William Weinert

The US Food and Drug Administration has granted 510(k) clearance for the BC-5390 Hematology Analyzer.

The product is designed to meet the testing needs of mid-volume hematology laboratories but offers features commonly found on large-volume analyzers.

The BC-5390 Hematology Analyzer provides a complete blood count with 21 parameters and a 5-part differential from a venous or capillary blood sample.

The product’s built-in autoloader has a 40-sample capacity, but it processes up to 60 samples per hour and stores up to 100,000 results with histograms.

The BC-5390 Hematology Analyzer’s barcode reader and optional laboratory information system connectivity enables seamless sample data transmission.

And nearly all scheduled maintenance procedures are automated by touch buttons.

The BC-5390 Hematology Analyzer is manufactured by Mindray, and MedTest will be the primary distributor of the analyzer in the US.

“We are excited to launch the BC-5390 Hematology Analyzer into the United States laboratory market,” said Caroline Li, general manager of Mindray IVD North America.

“The commercialization of the BC-5390 Hematology Analyzer in the US represents the first analyzer with a 5-part differential from Mindray.”

Blood samples

Photo by William Weinert

The US Food and Drug Administration has granted 510(k) clearance for the BC-5390 Hematology Analyzer.

The product is designed to meet the testing needs of mid-volume hematology laboratories but offers features commonly found on large-volume analyzers.

The BC-5390 Hematology Analyzer provides a complete blood count with 21 parameters and a 5-part differential from a venous or capillary blood sample.

The product’s built-in autoloader has a 40-sample capacity, but it processes up to 60 samples per hour and stores up to 100,000 results with histograms.

The BC-5390 Hematology Analyzer’s barcode reader and optional laboratory information system connectivity enables seamless sample data transmission.

And nearly all scheduled maintenance procedures are automated by touch buttons.

The BC-5390 Hematology Analyzer is manufactured by Mindray, and MedTest will be the primary distributor of the analyzer in the US.

“We are excited to launch the BC-5390 Hematology Analyzer into the United States laboratory market,” said Caroline Li, general manager of Mindray IVD North America.

“The commercialization of the BC-5390 Hematology Analyzer in the US represents the first analyzer with a 5-part differential from Mindray.”

Blood samples

Photo by William Weinert

The US Food and Drug Administration has granted 510(k) clearance for the BC-5390 Hematology Analyzer.

The product is designed to meet the testing needs of mid-volume hematology laboratories but offers features commonly found on large-volume analyzers.

The BC-5390 Hematology Analyzer provides a complete blood count with 21 parameters and a 5-part differential from a venous or capillary blood sample.

The product’s built-in autoloader has a 40-sample capacity, but it processes up to 60 samples per hour and stores up to 100,000 results with histograms.

The BC-5390 Hematology Analyzer’s barcode reader and optional laboratory information system connectivity enables seamless sample data transmission.

And nearly all scheduled maintenance procedures are automated by touch buttons.

The BC-5390 Hematology Analyzer is manufactured by Mindray, and MedTest will be the primary distributor of the analyzer in the US.

“We are excited to launch the BC-5390 Hematology Analyzer into the United States laboratory market,” said Caroline Li, general manager of Mindray IVD North America.

“The commercialization of the BC-5390 Hematology Analyzer in the US represents the first analyzer with a 5-part differential from Mindray.”

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.

“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”

Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.

Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.

The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.

Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.

Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.

“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.

The report did not use external funding, and the authors reported no relevant financial disclosures.

A surveillance project to evaluate the safety and effectiveness of transcarotid artery revascularization (TCAR) in comparison with carotid endarterectomy (CEA) is being launched by the Society for Vascular Surgery Patient Safety Organization (SVS PSO).  Carotid artery stenting (CAS) and CEA are performed in patients with atherosclerotic narrowing of the carotid artery in order to reduce stroke risk.  

In the TCAR procedure, a stent is inserted into the common carotid artery through a small neck incision (transcarotid), whereas typical carotid stents are inserted with a long catheter inserted in a groin artery (transfemoral) that must pass through the aorta to reach the carotid artery which is a potential source of stroke with the trans-femoral approach.   During TCAR, stroke risk is also reduced by temporarily reversing blood flow direction in the carotid artery, so that any debris dislodged by the procedure will not travel to the brain where it could cause stroke.  Initial publications suggest that TCAR may have a lower stroke rate than standard transfemoral CAS, potentially due to avoidance of a catheter manipulation in the aorta combined with carotid artery flow reversal.

The TCAR Surveillance Project is designed to obtain more data about real-world outcomes of TCAR in comparison with CEA as performed by centers participating in the Vascular Quality Initiative (VQI). The TCAR Surveillance Project will be directed by an SVS PSO Steering Committee that will make periodic analyses of data collected in the VQI CAS and CEA Registries.  

The TCAR Surveillance Project was evaluated by the US Food and Drug Administration (FDA) and found scientifically valid and clinically relevant.  Based on this, reimbursement for TCAR procedures performed by centers participating in the VQI TCAR Surveillance Project was approved on Sept. 1, 2016, by the Centers for Medicare and Medicaid Services (CMS) under the current National Coverage Determination.

The project requires that the procedure be performed in high surgical risk patients (asymptomatic or symptomatic) using FDA-approved or FDA-cleared devices labeled for the transcarotid approach and that data about the procedure and one-year follow-up be submitted to the VQI CAS Registry in order to qualify for Medicare coverage.  

“We are very pleased about this collaboration between the SVS PSO, CMS and the FDA that has enabled this important study,” said Dr. Larry Kraiss, Chair of the PSO Governing Council.  “It is through initiatives like the TCAR Surveillance Project that we can accomplish the SVS PSO mission, by using real-world registry data to evaluate and improve the care of our patients with carotid artery disease.”

Sites interested in participating in the project can enroll in the VQI CAS Registry if they do not already participate and obtain the National Clinical Trial identifier required for billing.

“The SVS applauds the efforts of its PSO to continually explore new and innovative ways to improve patient care,” said Dr. R. Clement Darling, President-Elect of the Society for Vascular Surgery.  “We are excited to learn what this study will find, and encourage participation in the TCAR Surveillance Project.”

For further information about participating in the VQI CAS registry, please contact vqi@m2s.com or call (603) 298-5509.

A surveillance project to evaluate the safety and effectiveness of transcarotid artery revascularization (TCAR) in comparison with carotid endarterectomy (CEA) is being launched by the Society for Vascular Surgery Patient Safety Organization (SVS PSO).  Carotid artery stenting (CAS) and CEA are performed in patients with atherosclerotic narrowing of the carotid artery in order to reduce stroke risk.  

In the TCAR procedure, a stent is inserted into the common carotid artery through a small neck incision (transcarotid), whereas typical carotid stents are inserted with a long catheter inserted in a groin artery (transfemoral) that must pass through the aorta to reach the carotid artery which is a potential source of stroke with the trans-femoral approach.   During TCAR, stroke risk is also reduced by temporarily reversing blood flow direction in the carotid artery, so that any debris dislodged by the procedure will not travel to the brain where it could cause stroke.  Initial publications suggest that TCAR may have a lower stroke rate than standard transfemoral CAS, potentially due to avoidance of a catheter manipulation in the aorta combined with carotid artery flow reversal.

The TCAR Surveillance Project is designed to obtain more data about real-world outcomes of TCAR in comparison with CEA as performed by centers participating in the Vascular Quality Initiative (VQI). The TCAR Surveillance Project will be directed by an SVS PSO Steering Committee that will make periodic analyses of data collected in the VQI CAS and CEA Registries.  

The TCAR Surveillance Project was evaluated by the US Food and Drug Administration (FDA) and found scientifically valid and clinically relevant.  Based on this, reimbursement for TCAR procedures performed by centers participating in the VQI TCAR Surveillance Project was approved on Sept. 1, 2016, by the Centers for Medicare and Medicaid Services (CMS) under the current National Coverage Determination.

The project requires that the procedure be performed in high surgical risk patients (asymptomatic or symptomatic) using FDA-approved or FDA-cleared devices labeled for the transcarotid approach and that data about the procedure and one-year follow-up be submitted to the VQI CAS Registry in order to qualify for Medicare coverage.  

“We are very pleased about this collaboration between the SVS PSO, CMS and the FDA that has enabled this important study,” said Dr. Larry Kraiss, Chair of the PSO Governing Council.  “It is through initiatives like the TCAR Surveillance Project that we can accomplish the SVS PSO mission, by using real-world registry data to evaluate and improve the care of our patients with carotid artery disease.”

Sites interested in participating in the project can enroll in the VQI CAS Registry if they do not already participate and obtain the National Clinical Trial identifier required for billing.

“The SVS applauds the efforts of its PSO to continually explore new and innovative ways to improve patient care,” said Dr. R. Clement Darling, President-Elect of the Society for Vascular Surgery.  “We are excited to learn what this study will find, and encourage participation in the TCAR Surveillance Project.”

For further information about participating in the VQI CAS registry, please contact vqi@m2s.com or call (603) 298-5509.

A surveillance project to evaluate the safety and effectiveness of transcarotid artery revascularization (TCAR) in comparison with carotid endarterectomy (CEA) is being launched by the Society for Vascular Surgery Patient Safety Organization (SVS PSO).  Carotid artery stenting (CAS) and CEA are performed in patients with atherosclerotic narrowing of the carotid artery in order to reduce stroke risk.  

In the TCAR procedure, a stent is inserted into the common carotid artery through a small neck incision (transcarotid), whereas typical carotid stents are inserted with a long catheter inserted in a groin artery (transfemoral) that must pass through the aorta to reach the carotid artery which is a potential source of stroke with the trans-femoral approach.   During TCAR, stroke risk is also reduced by temporarily reversing blood flow direction in the carotid artery, so that any debris dislodged by the procedure will not travel to the brain where it could cause stroke.  Initial publications suggest that TCAR may have a lower stroke rate than standard transfemoral CAS, potentially due to avoidance of a catheter manipulation in the aorta combined with carotid artery flow reversal.

The TCAR Surveillance Project is designed to obtain more data about real-world outcomes of TCAR in comparison with CEA as performed by centers participating in the Vascular Quality Initiative (VQI). The TCAR Surveillance Project will be directed by an SVS PSO Steering Committee that will make periodic analyses of data collected in the VQI CAS and CEA Registries.  

The TCAR Surveillance Project was evaluated by the US Food and Drug Administration (FDA) and found scientifically valid and clinically relevant.  Based on this, reimbursement for TCAR procedures performed by centers participating in the VQI TCAR Surveillance Project was approved on Sept. 1, 2016, by the Centers for Medicare and Medicaid Services (CMS) under the current National Coverage Determination.

The project requires that the procedure be performed in high surgical risk patients (asymptomatic or symptomatic) using FDA-approved or FDA-cleared devices labeled for the transcarotid approach and that data about the procedure and one-year follow-up be submitted to the VQI CAS Registry in order to qualify for Medicare coverage.  

“We are very pleased about this collaboration between the SVS PSO, CMS and the FDA that has enabled this important study,” said Dr. Larry Kraiss, Chair of the PSO Governing Council.  “It is through initiatives like the TCAR Surveillance Project that we can accomplish the SVS PSO mission, by using real-world registry data to evaluate and improve the care of our patients with carotid artery disease.”

Sites interested in participating in the project can enroll in the VQI CAS Registry if they do not already participate and obtain the National Clinical Trial identifier required for billing.

“The SVS applauds the efforts of its PSO to continually explore new and innovative ways to improve patient care,” said Dr. R. Clement Darling, President-Elect of the Society for Vascular Surgery.  “We are excited to learn what this study will find, and encourage participation in the TCAR Surveillance Project.”

For further information about participating in the VQI CAS registry, please contact vqi@m2s.com or call (603) 298-5509.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

LONDON – Four questions from the eight-question COPD Assessment Test (CAT) provide about the same prognostic accuracy in patients with chronic obstructive pulmonary disease (COPD) as does the full CAT, according to an analysis presented at the annual congress of the European Respiratory Society.

When the four- and eight-question versions were compared for exacerbation and other clinical outcomes over a 1-year period of follow-up, “both strategies demonstrated similar discrimination,” reported Carlos H. Martinez, MD, division of pulmonary and critical care medicine, University of Michigan Health System, Ann Arbor.

The CAT is an eight-item tool for evaluating the health status of patients with COPD as well as for predicting risk of COPD-related events, particularly exacerbations. The test is designed for self-administration by patients. For each of the questions, which address symptoms and activity limitations, patients are asked to answer on a scale ranging from one (indicating no clinical burden) to five (indicating severe burden). Based on the maximum score of 40, a score below 10 signifies a low impact from COPD, a score of 10-20 signifies a medium impact, and a score above 20 signifies a high impact.

©designer491/Thinkstock

In this study, a simplified version of the CAT that employed just four of the questions was evaluated in 880 participants in the observational SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study), which was funded by the National Heart, Lung, and Blood Institute and has prospectively enrolled COPD patients at seven participating centers. Ever-smokers from SPIROMICS were eligible for this analysis if they had a forced expiratory volume in one second (FEV₁₎/forced vital capacity (FVC) ratio of greater than or equal to 0.70 and an FVC above the lower limit of normal.

The four questions that were retained were about cough, phlegm, chest tightness, and breathlessness. The four questions that were eliminated were about activity limitation, sleep, energy, and the effect of lung symptoms on willingness to leave the house.

With the traditional test, using a cut point of greater than or equal to 10, 51.8% were classified as having a significant COPD burden. In this group, 15.3% experienced one or more exacerbations during 1 year of follow-up. With the simplified version focused on respiratory-related symptoms alone and using a cut point of greater than or equal to 7, 45.8% were classified as having a significant COPD burden, and 15.6% had one or more exacerbations during the same period of follow-up.

“The two strategies largely identified the same individuals,” according to Dr. Martinez, who reported the agreement as 88.5% (Kappa 0.77; P less than .001). He further noted that there was no difference in the area under the curve (AUC) to predict exacerbations at 1 year.

In further analysis, “subjects identified by either method also had more depression and anxiety symptoms, poorer sleep quality, and greater fatigue [than did the lower risk group],” Dr. Martinez added.

An AUC ROC (receiver operating characteristic) statistical analysis to compare the traditional and abbreviated CATs for cross-sectional associations showed close agreement. The values were nearly identical for such variables as dyspnea, impairment as measured with the 6-minute walking distance (6MWD) test, and quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ). Similarly, the AUC ROC values diverged little or not at all for longitudinal comparisons of any exacerbation or exacerbations requiring steroids or antibiotics.

The data from this study provide “a proof of concept that simpler strategies could be used for identifying these patients [at risk of exacerbations] in primary care,” Dr. Martinez maintained. Although further validation of this four-question assessment tool is needed, Dr. Martinez implied that there is value in a relatively rapid self-assessment tool that could be interpreted quickly by clinicians.

LONDON – Four questions from the eight-question COPD Assessment Test (CAT) provide about the same prognostic accuracy in patients with chronic obstructive pulmonary disease (COPD) as does the full CAT, according to an analysis presented at the annual congress of the European Respiratory Society.

When the four- and eight-question versions were compared for exacerbation and other clinical outcomes over a 1-year period of follow-up, “both strategies demonstrated similar discrimination,” reported Carlos H. Martinez, MD, division of pulmonary and critical care medicine, University of Michigan Health System, Ann Arbor.

The CAT is an eight-item tool for evaluating the health status of patients with COPD as well as for predicting risk of COPD-related events, particularly exacerbations. The test is designed for self-administration by patients. For each of the questions, which address symptoms and activity limitations, patients are asked to answer on a scale ranging from one (indicating no clinical burden) to five (indicating severe burden). Based on the maximum score of 40, a score below 10 signifies a low impact from COPD, a score of 10-20 signifies a medium impact, and a score above 20 signifies a high impact.

©designer491/Thinkstock

In this study, a simplified version of the CAT that employed just four of the questions was evaluated in 880 participants in the observational SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study), which was funded by the National Heart, Lung, and Blood Institute and has prospectively enrolled COPD patients at seven participating centers. Ever-smokers from SPIROMICS were eligible for this analysis if they had a forced expiratory volume in one second (FEV₁₎/forced vital capacity (FVC) ratio of greater than or equal to 0.70 and an FVC above the lower limit of normal.

The four questions that were retained were about cough, phlegm, chest tightness, and breathlessness. The four questions that were eliminated were about activity limitation, sleep, energy, and the effect of lung symptoms on willingness to leave the house.

With the traditional test, using a cut point of greater than or equal to 10, 51.8% were classified as having a significant COPD burden. In this group, 15.3% experienced one or more exacerbations during 1 year of follow-up. With the simplified version focused on respiratory-related symptoms alone and using a cut point of greater than or equal to 7, 45.8% were classified as having a significant COPD burden, and 15.6% had one or more exacerbations during the same period of follow-up.

“The two strategies largely identified the same individuals,” according to Dr. Martinez, who reported the agreement as 88.5% (Kappa 0.77; P less than .001). He further noted that there was no difference in the area under the curve (AUC) to predict exacerbations at 1 year.

In further analysis, “subjects identified by either method also had more depression and anxiety symptoms, poorer sleep quality, and greater fatigue [than did the lower risk group],” Dr. Martinez added.

An AUC ROC (receiver operating characteristic) statistical analysis to compare the traditional and abbreviated CATs for cross-sectional associations showed close agreement. The values were nearly identical for such variables as dyspnea, impairment as measured with the 6-minute walking distance (6MWD) test, and quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ). Similarly, the AUC ROC values diverged little or not at all for longitudinal comparisons of any exacerbation or exacerbations requiring steroids or antibiotics.

The data from this study provide “a proof of concept that simpler strategies could be used for identifying these patients [at risk of exacerbations] in primary care,” Dr. Martinez maintained. Although further validation of this four-question assessment tool is needed, Dr. Martinez implied that there is value in a relatively rapid self-assessment tool that could be interpreted quickly by clinicians.

LONDON – Four questions from the eight-question COPD Assessment Test (CAT) provide about the same prognostic accuracy in patients with chronic obstructive pulmonary disease (COPD) as does the full CAT, according to an analysis presented at the annual congress of the European Respiratory Society.

When the four- and eight-question versions were compared for exacerbation and other clinical outcomes over a 1-year period of follow-up, “both strategies demonstrated similar discrimination,” reported Carlos H. Martinez, MD, division of pulmonary and critical care medicine, University of Michigan Health System, Ann Arbor.

The CAT is an eight-item tool for evaluating the health status of patients with COPD as well as for predicting risk of COPD-related events, particularly exacerbations. The test is designed for self-administration by patients. For each of the questions, which address symptoms and activity limitations, patients are asked to answer on a scale ranging from one (indicating no clinical burden) to five (indicating severe burden). Based on the maximum score of 40, a score below 10 signifies a low impact from COPD, a score of 10-20 signifies a medium impact, and a score above 20 signifies a high impact.

©designer491/Thinkstock

In this study, a simplified version of the CAT that employed just four of the questions was evaluated in 880 participants in the observational SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study), which was funded by the National Heart, Lung, and Blood Institute and has prospectively enrolled COPD patients at seven participating centers. Ever-smokers from SPIROMICS were eligible for this analysis if they had a forced expiratory volume in one second (FEV₁₎/forced vital capacity (FVC) ratio of greater than or equal to 0.70 and an FVC above the lower limit of normal.

The four questions that were retained were about cough, phlegm, chest tightness, and breathlessness. The four questions that were eliminated were about activity limitation, sleep, energy, and the effect of lung symptoms on willingness to leave the house.

With the traditional test, using a cut point of greater than or equal to 10, 51.8% were classified as having a significant COPD burden. In this group, 15.3% experienced one or more exacerbations during 1 year of follow-up. With the simplified version focused on respiratory-related symptoms alone and using a cut point of greater than or equal to 7, 45.8% were classified as having a significant COPD burden, and 15.6% had one or more exacerbations during the same period of follow-up.

“The two strategies largely identified the same individuals,” according to Dr. Martinez, who reported the agreement as 88.5% (Kappa 0.77; P less than .001). He further noted that there was no difference in the area under the curve (AUC) to predict exacerbations at 1 year.

In further analysis, “subjects identified by either method also had more depression and anxiety symptoms, poorer sleep quality, and greater fatigue [than did the lower risk group],” Dr. Martinez added.

An AUC ROC (receiver operating characteristic) statistical analysis to compare the traditional and abbreviated CATs for cross-sectional associations showed close agreement. The values were nearly identical for such variables as dyspnea, impairment as measured with the 6-minute walking distance (6MWD) test, and quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ). Similarly, the AUC ROC values diverged little or not at all for longitudinal comparisons of any exacerbation or exacerbations requiring steroids or antibiotics.

The data from this study provide “a proof of concept that simpler strategies could be used for identifying these patients [at risk of exacerbations] in primary care,” Dr. Martinez maintained. Although further validation of this four-question assessment tool is needed, Dr. Martinez implied that there is value in a relatively rapid self-assessment tool that could be interpreted quickly by clinicians.

The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.

The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.

“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”

But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.

“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”

The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.

The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.

During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.

Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.

“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”

Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.

But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.

“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”

Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.

“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.

agallegos@frontlinemedcom.com

On Twitter @legal_med

The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.

The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.

“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”

But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.

“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”

The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.

The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.

During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.

Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.

“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”

Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.

But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.

“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”

Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.

“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.

agallegos@frontlinemedcom.com

On Twitter @legal_med

The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.

The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.

“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”

But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.

“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”

The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.

The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.

During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.

Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.

“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”

Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.

But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.

“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”

Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.

“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.

agallegos@frontlinemedcom.com

On Twitter @legal_med