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Atrial fibrillation blunts beta-blockers for HFrEF
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: All-cause mortality was similar in patients with HFrEF and atrial fibrillation regardless of whether they received a beta-blocker or placebo.
Data source: BB-META-HF, a meta-analysis of 11 beta-blocker treatment trials with 17,378 HFrEF patients.
Disclosures: BB-META-HF received funding from Menarini and GlaxoSmithKline. Dr. Cleland has received research funding and honoraria from GlaxoSmithKline.
Immediate-completion lymph node dissection in metastatic melanoma
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%).
Data source: A prospective international randomized phase-III trial involving 1,939 adults followed for a median of 43 months at 63 medical centers.
Disclosures: This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
Quality measures and diabetic foot care: What endos need to know
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
IL-23 antibody risankizumab can effect, maintain remission in Crohn’s
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: By week 52, clinical remission was maintained in 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo.
Disclosures: Dr. Feagan reported financial relationships with Boehringer Ingelheim and AbbVie.
Dual SGLT1-2 inhibitor improved glycemic control in T1DM
SAN DIEGO – levels to less than 7% without severe diabetic ketoacidosis or hypoglycemia, compared with placebo, in a pivotal phase III trial of adults with type 1 diabetes.
After 24 weeks, 58 (22%) of patients on placebo achieved this combined endpoint, compared with 44% of patients who received 400 mg oral daily sotagliflozin (P less than .001) and 34% of those who received 200 mg (P = .002), John B. Buse, MD, PhD, reported at the annual scientific sessions of the American Diabetes Association. “Sotagliflozin significantly reduced hemoglobin A1c in the setting of optimized insulin therapy, with a safety profile that supports further clinical development,” said Dr. Buse, lead investigator of the Tandem1 trial.
To further evaluate the efficacy and safety of adjunctive sotagliflozin for type 1 diabetes, Dr. Buse and his associates randomly assigned 793 patients from 75 North American sites to receive either placebo or treatment at 200 mg or 400 mg for 24 weeks. Patients and investigators were blinded as to treatment arm. Patients received optimized insulin, and the trial arms were demographically and clinically similar at baseline. The average age was 46 years, mean body mass index was 30 kg per m2, average daily insulin dose was 0.73 U per kg, and mean baseline HbA1c was 7.58 % (standard deviation, 0.73%).
By week 24, HbA1c levels fell by an average of 8% on placebo, 43% on 200 mg sotagliflozin, and 49% on 400 mg sotagliflozin, Dr. Buse reported. “The decrease from baseline was highly significant at both doses of sotagliflozin, compared with placebo,” he noted. Adjunctive sotagliflozin therapy also led to significant reductions in bolus insulin doses, fasting blood glucose levels, and body weight as compared with placebo. Drops in body weight averaged 1.6 kg at 200 mg and 2.7 kg at 400 mg, while placebo patients gained an average of 0.8 kg.
There were no deaths during the trial. Rates of treatment-associated adverse events were similar across groups, and serious adverse events affected 3% of placebo patients, 4% of 200-mg patients, and 7% of 400-mg patients. In all, 7% of placebo recipients experienced severe hypoglycemia, compared with 4%-5% of patients on sotagliflozin. The incidence of DKA was 0% on placebo and 1%-3% on sotagliflozin, with a higher rate among patients on pumps, Dr. Buse noted. Most cases of DKA were considered mildly to moderately severe, with blood glucose levels under 250 mg per dL, he added. Sotagliflozin also was associated with dose-dependent increases in rates of diarrhea and genital mycotic infections, which reached about 10% in the 400-mg arm. However, less than 1% of patients stopped treatment because of either adverse event.
“This is the first report of a successful phase III trial of an oral antidiabetic as an adjunct to insulin therapy for type 1 diabetes,” Dr. Buse commented. Sotagliflozin met all prespecified endpoints in the trial, and the 400-mg dose significantly outperformed placebo on each endpoint, he added. A second phase III trial of sotagliflozin (inTandem2) is ongoing, and investigators plan to present pooled data from both trials later this year. Meanwhile, a third phase III trial (inTandem3) is comparing 400 mg sotagliflozin or placebo for patients receiving any type of insulin therapy.
Lexicon Pharmaceuticals developed sotagliflozin and funded the study. Dr. Buse disclosed research funding from Lexicon, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, and several other pharmaceutical companies.
SAN DIEGO – levels to less than 7% without severe diabetic ketoacidosis or hypoglycemia, compared with placebo, in a pivotal phase III trial of adults with type 1 diabetes.
After 24 weeks, 58 (22%) of patients on placebo achieved this combined endpoint, compared with 44% of patients who received 400 mg oral daily sotagliflozin (P less than .001) and 34% of those who received 200 mg (P = .002), John B. Buse, MD, PhD, reported at the annual scientific sessions of the American Diabetes Association. “Sotagliflozin significantly reduced hemoglobin A1c in the setting of optimized insulin therapy, with a safety profile that supports further clinical development,” said Dr. Buse, lead investigator of the Tandem1 trial.
To further evaluate the efficacy and safety of adjunctive sotagliflozin for type 1 diabetes, Dr. Buse and his associates randomly assigned 793 patients from 75 North American sites to receive either placebo or treatment at 200 mg or 400 mg for 24 weeks. Patients and investigators were blinded as to treatment arm. Patients received optimized insulin, and the trial arms were demographically and clinically similar at baseline. The average age was 46 years, mean body mass index was 30 kg per m2, average daily insulin dose was 0.73 U per kg, and mean baseline HbA1c was 7.58 % (standard deviation, 0.73%).
By week 24, HbA1c levels fell by an average of 8% on placebo, 43% on 200 mg sotagliflozin, and 49% on 400 mg sotagliflozin, Dr. Buse reported. “The decrease from baseline was highly significant at both doses of sotagliflozin, compared with placebo,” he noted. Adjunctive sotagliflozin therapy also led to significant reductions in bolus insulin doses, fasting blood glucose levels, and body weight as compared with placebo. Drops in body weight averaged 1.6 kg at 200 mg and 2.7 kg at 400 mg, while placebo patients gained an average of 0.8 kg.
There were no deaths during the trial. Rates of treatment-associated adverse events were similar across groups, and serious adverse events affected 3% of placebo patients, 4% of 200-mg patients, and 7% of 400-mg patients. In all, 7% of placebo recipients experienced severe hypoglycemia, compared with 4%-5% of patients on sotagliflozin. The incidence of DKA was 0% on placebo and 1%-3% on sotagliflozin, with a higher rate among patients on pumps, Dr. Buse noted. Most cases of DKA were considered mildly to moderately severe, with blood glucose levels under 250 mg per dL, he added. Sotagliflozin also was associated with dose-dependent increases in rates of diarrhea and genital mycotic infections, which reached about 10% in the 400-mg arm. However, less than 1% of patients stopped treatment because of either adverse event.
“This is the first report of a successful phase III trial of an oral antidiabetic as an adjunct to insulin therapy for type 1 diabetes,” Dr. Buse commented. Sotagliflozin met all prespecified endpoints in the trial, and the 400-mg dose significantly outperformed placebo on each endpoint, he added. A second phase III trial of sotagliflozin (inTandem2) is ongoing, and investigators plan to present pooled data from both trials later this year. Meanwhile, a third phase III trial (inTandem3) is comparing 400 mg sotagliflozin or placebo for patients receiving any type of insulin therapy.
Lexicon Pharmaceuticals developed sotagliflozin and funded the study. Dr. Buse disclosed research funding from Lexicon, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, and several other pharmaceutical companies.
SAN DIEGO – levels to less than 7% without severe diabetic ketoacidosis or hypoglycemia, compared with placebo, in a pivotal phase III trial of adults with type 1 diabetes.
After 24 weeks, 58 (22%) of patients on placebo achieved this combined endpoint, compared with 44% of patients who received 400 mg oral daily sotagliflozin (P less than .001) and 34% of those who received 200 mg (P = .002), John B. Buse, MD, PhD, reported at the annual scientific sessions of the American Diabetes Association. “Sotagliflozin significantly reduced hemoglobin A1c in the setting of optimized insulin therapy, with a safety profile that supports further clinical development,” said Dr. Buse, lead investigator of the Tandem1 trial.
To further evaluate the efficacy and safety of adjunctive sotagliflozin for type 1 diabetes, Dr. Buse and his associates randomly assigned 793 patients from 75 North American sites to receive either placebo or treatment at 200 mg or 400 mg for 24 weeks. Patients and investigators were blinded as to treatment arm. Patients received optimized insulin, and the trial arms were demographically and clinically similar at baseline. The average age was 46 years, mean body mass index was 30 kg per m2, average daily insulin dose was 0.73 U per kg, and mean baseline HbA1c was 7.58 % (standard deviation, 0.73%).
By week 24, HbA1c levels fell by an average of 8% on placebo, 43% on 200 mg sotagliflozin, and 49% on 400 mg sotagliflozin, Dr. Buse reported. “The decrease from baseline was highly significant at both doses of sotagliflozin, compared with placebo,” he noted. Adjunctive sotagliflozin therapy also led to significant reductions in bolus insulin doses, fasting blood glucose levels, and body weight as compared with placebo. Drops in body weight averaged 1.6 kg at 200 mg and 2.7 kg at 400 mg, while placebo patients gained an average of 0.8 kg.
There were no deaths during the trial. Rates of treatment-associated adverse events were similar across groups, and serious adverse events affected 3% of placebo patients, 4% of 200-mg patients, and 7% of 400-mg patients. In all, 7% of placebo recipients experienced severe hypoglycemia, compared with 4%-5% of patients on sotagliflozin. The incidence of DKA was 0% on placebo and 1%-3% on sotagliflozin, with a higher rate among patients on pumps, Dr. Buse noted. Most cases of DKA were considered mildly to moderately severe, with blood glucose levels under 250 mg per dL, he added. Sotagliflozin also was associated with dose-dependent increases in rates of diarrhea and genital mycotic infections, which reached about 10% in the 400-mg arm. However, less than 1% of patients stopped treatment because of either adverse event.
“This is the first report of a successful phase III trial of an oral antidiabetic as an adjunct to insulin therapy for type 1 diabetes,” Dr. Buse commented. Sotagliflozin met all prespecified endpoints in the trial, and the 400-mg dose significantly outperformed placebo on each endpoint, he added. A second phase III trial of sotagliflozin (inTandem2) is ongoing, and investigators plan to present pooled data from both trials later this year. Meanwhile, a third phase III trial (inTandem3) is comparing 400 mg sotagliflozin or placebo for patients receiving any type of insulin therapy.
Lexicon Pharmaceuticals developed sotagliflozin and funded the study. Dr. Buse disclosed research funding from Lexicon, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, and several other pharmaceutical companies.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: Augmenting optimized insulin with a dual SGLT1-2 inhibitor significantly increased the chances of improved glycemic control without severe hypoglycemia or diabetic ketoacidosis in adults with type 1 diabetes.
Major finding: After 24 weeks, 22% of the placebo group achieved this combined endpoint, compared with 44% of patients receiving 400 mg oral daily sotagliflozin (P less than .001) and 34% of patients receiving 200 mg (P = .002).
Data source: A multicenter, randomized, double-blind phase III trial of 793 adults with type 1 diabetes.
Disclosures: Lexicon Pharmaceuticals developed sotagliflozin and funded the study. Dr. Buse disclosed research funding from Lexicon, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, and several other pharmaceutical companies.
Majority of AML patients do not receive recommended molecular genetic testing
CHICAGO—While 67% of newly diagnosed patients with acute myeloid leukemia (AML) receive some genetic testing, only 9% receive all 7 of the genetic tests recommended by the National Comprehensive Cancer Network (NCCN), according to new research.
The data comes from the CONNECT MDS/AML Disease Registry, which collects treatment and outcome statistics from 86 sites across the United States, both academic medical centers and community settings. The findings reflect data gathered from 2013 to 2016.
Previously, data on genetic testing in AML patients came primarily from clinical trials, where adherence to guidelines is very high. The current analysis evaluated adherence to genetic testing guidelines in AML treated outside the clinic trial setting.
Daniel A. Pollyea, MD, of the University of Colorado Comprehensive Cancer Center in Aurora, presented the findings on behalf of the CONNECT MDS/AML Disease Registry Scientific Steering Committee (abstract 7022).
The CONNECT registry is a US prospective, observational cohort study of patients with newly diagnosed AML or myelodysplastic syndromes (MDS) aged 55 years or older. Enrollment is ongoing and study clinicians make all clinical decisions.
NCCN guidelines recommend testing AML patients for NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, DNMT3A, and KIT mutations.
“We now know a tremendous amount about the genetic underpinnings of the disease,” Dr Pollyea said.
“We can test for these genetic changes in the clinic to see what’s making a patient’s disease tick. And often there are targeted therapies that can be matched with these genetic changes," he added. "But there’s a disconnect between what can be done, what should be done, and what is being done.”
The current analysis evaluated genetic testing in 259 AML patients, 173 (67%) of whom had some genetic testing.
The likelihood of patients getting tested varied by type of treatment center, age, karyotype, and insurance.
Patients treated at academic medical centers had higher rates of testing than those treated at community clinics (76% and 62%, respectively), P= 0.018
Patients younger than 65 years more often were tested than older patients (83% and 60%, respectively), P= 0.0003.
Patients with non-Medicare insurance were more often tested than those with Medicare (74% and 61%, respectively), P= .025.
And patients with normal karyotype were more often tested than those with abnormal karyotype (77% and 59%, respectively), P= 0.006.
Of the 173 patients who had some genetic testing, only 15 (9%) had all the molecular tests recommended by NCCN.
Of the 7 recommended tests, NPM1 (77%) and FLT3-ITD (76%) were most often reported and DNMT3A least often (16%).
Dr Pollyea attributed the lack of adherence to the guidelines in part to willingness of insurance companies to pay for testing.
He also suggested the guidelines themselves might need adjustment, given the low adherence rate.
Nevertheless, he affirmed the guidelines are well founded. “I think the guidelines are pretty solid and, in my opinion, I would say they don’t go far enough in recommending genetic testing.”
“We’re in our infancy with this testing, and even earlier than infancy in seeing how we’re doing on testing. But now with this registry we at least have the infrastructure available to ask these kinds of questions,” Dr Pollyea added. 
CHICAGO—While 67% of newly diagnosed patients with acute myeloid leukemia (AML) receive some genetic testing, only 9% receive all 7 of the genetic tests recommended by the National Comprehensive Cancer Network (NCCN), according to new research.
The data comes from the CONNECT MDS/AML Disease Registry, which collects treatment and outcome statistics from 86 sites across the United States, both academic medical centers and community settings. The findings reflect data gathered from 2013 to 2016.
Previously, data on genetic testing in AML patients came primarily from clinical trials, where adherence to guidelines is very high. The current analysis evaluated adherence to genetic testing guidelines in AML treated outside the clinic trial setting.
Daniel A. Pollyea, MD, of the University of Colorado Comprehensive Cancer Center in Aurora, presented the findings on behalf of the CONNECT MDS/AML Disease Registry Scientific Steering Committee (abstract 7022).
The CONNECT registry is a US prospective, observational cohort study of patients with newly diagnosed AML or myelodysplastic syndromes (MDS) aged 55 years or older. Enrollment is ongoing and study clinicians make all clinical decisions.
NCCN guidelines recommend testing AML patients for NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, DNMT3A, and KIT mutations.
“We now know a tremendous amount about the genetic underpinnings of the disease,” Dr Pollyea said.
“We can test for these genetic changes in the clinic to see what’s making a patient’s disease tick. And often there are targeted therapies that can be matched with these genetic changes," he added. "But there’s a disconnect between what can be done, what should be done, and what is being done.”
The current analysis evaluated genetic testing in 259 AML patients, 173 (67%) of whom had some genetic testing.
The likelihood of patients getting tested varied by type of treatment center, age, karyotype, and insurance.
Patients treated at academic medical centers had higher rates of testing than those treated at community clinics (76% and 62%, respectively), P= 0.018
Patients younger than 65 years more often were tested than older patients (83% and 60%, respectively), P= 0.0003.
Patients with non-Medicare insurance were more often tested than those with Medicare (74% and 61%, respectively), P= .025.
And patients with normal karyotype were more often tested than those with abnormal karyotype (77% and 59%, respectively), P= 0.006.
Of the 173 patients who had some genetic testing, only 15 (9%) had all the molecular tests recommended by NCCN.
Of the 7 recommended tests, NPM1 (77%) and FLT3-ITD (76%) were most often reported and DNMT3A least often (16%).
Dr Pollyea attributed the lack of adherence to the guidelines in part to willingness of insurance companies to pay for testing.
He also suggested the guidelines themselves might need adjustment, given the low adherence rate.
Nevertheless, he affirmed the guidelines are well founded. “I think the guidelines are pretty solid and, in my opinion, I would say they don’t go far enough in recommending genetic testing.”
“We’re in our infancy with this testing, and even earlier than infancy in seeing how we’re doing on testing. But now with this registry we at least have the infrastructure available to ask these kinds of questions,” Dr Pollyea added.
CHICAGO—While 67% of newly diagnosed patients with acute myeloid leukemia (AML) receive some genetic testing, only 9% receive all 7 of the genetic tests recommended by the National Comprehensive Cancer Network (NCCN), according to new research.
The data comes from the CONNECT MDS/AML Disease Registry, which collects treatment and outcome statistics from 86 sites across the United States, both academic medical centers and community settings. The findings reflect data gathered from 2013 to 2016.
Previously, data on genetic testing in AML patients came primarily from clinical trials, where adherence to guidelines is very high. The current analysis evaluated adherence to genetic testing guidelines in AML treated outside the clinic trial setting.
Daniel A. Pollyea, MD, of the University of Colorado Comprehensive Cancer Center in Aurora, presented the findings on behalf of the CONNECT MDS/AML Disease Registry Scientific Steering Committee (abstract 7022).
The CONNECT registry is a US prospective, observational cohort study of patients with newly diagnosed AML or myelodysplastic syndromes (MDS) aged 55 years or older. Enrollment is ongoing and study clinicians make all clinical decisions.
NCCN guidelines recommend testing AML patients for NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, DNMT3A, and KIT mutations.
“We now know a tremendous amount about the genetic underpinnings of the disease,” Dr Pollyea said.
“We can test for these genetic changes in the clinic to see what’s making a patient’s disease tick. And often there are targeted therapies that can be matched with these genetic changes," he added. "But there’s a disconnect between what can be done, what should be done, and what is being done.”
The current analysis evaluated genetic testing in 259 AML patients, 173 (67%) of whom had some genetic testing.
The likelihood of patients getting tested varied by type of treatment center, age, karyotype, and insurance.
Patients treated at academic medical centers had higher rates of testing than those treated at community clinics (76% and 62%, respectively), P= 0.018
Patients younger than 65 years more often were tested than older patients (83% and 60%, respectively), P= 0.0003.
Patients with non-Medicare insurance were more often tested than those with Medicare (74% and 61%, respectively), P= .025.
And patients with normal karyotype were more often tested than those with abnormal karyotype (77% and 59%, respectively), P= 0.006.
Of the 173 patients who had some genetic testing, only 15 (9%) had all the molecular tests recommended by NCCN.
Of the 7 recommended tests, NPM1 (77%) and FLT3-ITD (76%) were most often reported and DNMT3A least often (16%).
Dr Pollyea attributed the lack of adherence to the guidelines in part to willingness of insurance companies to pay for testing.
He also suggested the guidelines themselves might need adjustment, given the low adherence rate.
Nevertheless, he affirmed the guidelines are well founded. “I think the guidelines are pretty solid and, in my opinion, I would say they don’t go far enough in recommending genetic testing.”
“We’re in our infancy with this testing, and even earlier than infancy in seeing how we’re doing on testing. But now with this registry we at least have the infrastructure available to ask these kinds of questions,” Dr Pollyea added.
Bedside CGM boosts glucose control in hospital
BY RANDY DOTINGA
SAN DIEGO – Bedside continuous glucose monitoring (CGM) with a wireless hookup to a response team allowed doctors and nurses to gain better blood sugar control in hospitalized high-risk patients with diabetes, according to research reported at the annual scientific sessions of the American Diabetes Association.
“Continuous glucose monitoring and wireless connections can be useful in the hospital setting, not just in the outpatient setting,” said Maria Isabel Garcia, RN, of Scripps Whittier Diabetes Institute. “They help us to prevent problems rather than fixing them after they happen.”
Research suggests that complications due to dangerous blood sugar levels can lead to longer hospital stays, she noted.
For the study, researchers assigned 45 high-risk hospitalized patients with type 2 diabetes to be monitored by DexCom G4 CGM devices. The patients were being treated for a variety of conditions, and all were expected to be hospitalized for more than 2 days.
Researchers housed the normal-sized CGM devices in toolbox-sized containers at bedside. “We don’t want the equipment to get misplaced if the patient has to go from room to room or if the patient is discharged and takes the equipment by mistake,” Ms. Garcia said.
The patients were 43-82 years old (median, 61.4 years; standard deviation, 9.8), 56% male, 73% Hispanic (with 60% preferring to speak Spanish). The mean hemoglobin A1c was 10.2% (SD, 2.3), and the mean body mass index was 32.9 (SD, 8).
The patients were randomized to two groups. In both, the CGM devices were operative and tracked blood sugar levels. In one group, the information was transmitted via wireless hookup to a team of researchers (during the day) or a telemetry team (at night), who were alerted via alarms if blood sugar levels seemed too high or low. The teams would then alert nurses who’d confirm the levels via bedside testing and take appropriate action.
CGM data were gathered from the patients for an average of 4.2 days each (SD, 2.49; range 2-10), and the number of readings per patient ranged from 102 to 2,334 each (median 859.4; SD, 627.8).
The findings suggest that wireless transmission of CGM allowed hospital staff to improve blood sugar control. Readings under 70 mg/dL occurred 0.7% of the time in patients monitored via wireless hookup and 1.4% in the others. Readings over 250 mg/dL appeared 9.8% and 13.2% of the time, respectively and readings over 300 mg/dL appeared 2.6% and 5.1% of the time, respectively.
The investigators plan to recruit 460 patients for the study, Ms. Garcia said. Results may be available within a couple of years, she said.
DexCom provided the CGM devices for the study, which was funded by Diabetes Research Connection and the Confidence Foundation. Ms. Garcia reports no disclosures.
BY RANDY DOTINGA
SAN DIEGO – Bedside continuous glucose monitoring (CGM) with a wireless hookup to a response team allowed doctors and nurses to gain better blood sugar control in hospitalized high-risk patients with diabetes, according to research reported at the annual scientific sessions of the American Diabetes Association.
“Continuous glucose monitoring and wireless connections can be useful in the hospital setting, not just in the outpatient setting,” said Maria Isabel Garcia, RN, of Scripps Whittier Diabetes Institute. “They help us to prevent problems rather than fixing them after they happen.”
Research suggests that complications due to dangerous blood sugar levels can lead to longer hospital stays, she noted.
For the study, researchers assigned 45 high-risk hospitalized patients with type 2 diabetes to be monitored by DexCom G4 CGM devices. The patients were being treated for a variety of conditions, and all were expected to be hospitalized for more than 2 days.
Researchers housed the normal-sized CGM devices in toolbox-sized containers at bedside. “We don’t want the equipment to get misplaced if the patient has to go from room to room or if the patient is discharged and takes the equipment by mistake,” Ms. Garcia said.
The patients were 43-82 years old (median, 61.4 years; standard deviation, 9.8), 56% male, 73% Hispanic (with 60% preferring to speak Spanish). The mean hemoglobin A1c was 10.2% (SD, 2.3), and the mean body mass index was 32.9 (SD, 8).
The patients were randomized to two groups. In both, the CGM devices were operative and tracked blood sugar levels. In one group, the information was transmitted via wireless hookup to a team of researchers (during the day) or a telemetry team (at night), who were alerted via alarms if blood sugar levels seemed too high or low. The teams would then alert nurses who’d confirm the levels via bedside testing and take appropriate action.
CGM data were gathered from the patients for an average of 4.2 days each (SD, 2.49; range 2-10), and the number of readings per patient ranged from 102 to 2,334 each (median 859.4; SD, 627.8).
The findings suggest that wireless transmission of CGM allowed hospital staff to improve blood sugar control. Readings under 70 mg/dL occurred 0.7% of the time in patients monitored via wireless hookup and 1.4% in the others. Readings over 250 mg/dL appeared 9.8% and 13.2% of the time, respectively and readings over 300 mg/dL appeared 2.6% and 5.1% of the time, respectively.
The investigators plan to recruit 460 patients for the study, Ms. Garcia said. Results may be available within a couple of years, she said.
DexCom provided the CGM devices for the study, which was funded by Diabetes Research Connection and the Confidence Foundation. Ms. Garcia reports no disclosures.
BY RANDY DOTINGA
SAN DIEGO – Bedside continuous glucose monitoring (CGM) with a wireless hookup to a response team allowed doctors and nurses to gain better blood sugar control in hospitalized high-risk patients with diabetes, according to research reported at the annual scientific sessions of the American Diabetes Association.
“Continuous glucose monitoring and wireless connections can be useful in the hospital setting, not just in the outpatient setting,” said Maria Isabel Garcia, RN, of Scripps Whittier Diabetes Institute. “They help us to prevent problems rather than fixing them after they happen.”
Research suggests that complications due to dangerous blood sugar levels can lead to longer hospital stays, she noted.
For the study, researchers assigned 45 high-risk hospitalized patients with type 2 diabetes to be monitored by DexCom G4 CGM devices. The patients were being treated for a variety of conditions, and all were expected to be hospitalized for more than 2 days.
Researchers housed the normal-sized CGM devices in toolbox-sized containers at bedside. “We don’t want the equipment to get misplaced if the patient has to go from room to room or if the patient is discharged and takes the equipment by mistake,” Ms. Garcia said.
The patients were 43-82 years old (median, 61.4 years; standard deviation, 9.8), 56% male, 73% Hispanic (with 60% preferring to speak Spanish). The mean hemoglobin A1c was 10.2% (SD, 2.3), and the mean body mass index was 32.9 (SD, 8).
The patients were randomized to two groups. In both, the CGM devices were operative and tracked blood sugar levels. In one group, the information was transmitted via wireless hookup to a team of researchers (during the day) or a telemetry team (at night), who were alerted via alarms if blood sugar levels seemed too high or low. The teams would then alert nurses who’d confirm the levels via bedside testing and take appropriate action.
CGM data were gathered from the patients for an average of 4.2 days each (SD, 2.49; range 2-10), and the number of readings per patient ranged from 102 to 2,334 each (median 859.4; SD, 627.8).
The findings suggest that wireless transmission of CGM allowed hospital staff to improve blood sugar control. Readings under 70 mg/dL occurred 0.7% of the time in patients monitored via wireless hookup and 1.4% in the others. Readings over 250 mg/dL appeared 9.8% and 13.2% of the time, respectively and readings over 300 mg/dL appeared 2.6% and 5.1% of the time, respectively.
The investigators plan to recruit 460 patients for the study, Ms. Garcia said. Results may be available within a couple of years, she said.
DexCom provided the CGM devices for the study, which was funded by Diabetes Research Connection and the Confidence Foundation. Ms. Garcia reports no disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: about high or low readings.
Major finding: Readings under 70 mg/dL occurred 0.7% of the time in patients monitored via wireless hookup and 1.4% in other patients. Readings over 250 mg/dL appeared 9.8% and 13.2% of the time, respectively, and readings over 300 mg/dL appeared 2.6% and 5.1% of the time, respectively.
Data source: Early results from a pilot randomized, controlled study of 45 hospitalized, high-risk patients with type 2 diabetes. CGM devices measured glucose levels in all patients, but they were only transmitted via wireless hookup to teams in one group.
Disclosures: DexCom provided the CGM machines for the study, which was funded by Diabetes Research Connection and the Confidence Foundation. Garcia reports no disclosures.
Rapid culture, stewardship improve S. aureus bacteremia outcomes
NEW ORLEANS – Community hospitals could see positive outcomes using a Staphylococcus aureus bacteremia strategy that combines rapid blood cultures to speed diagnosis with antibiotic stewardship to guide treatment.
Many academic medical centers report improved outcomes with this approach. Now a study of 66 patients at a medium-sized hospital in rural North Dakota suggests this strategy translates well to the community hospital setting and can reduce mortality and 30-day readmission rates, and increase cost-effectiveness overall.
“I was pleased to see we were able to replicate the positive outcomes observed in studies from large tertiary care centers with our small cohort,” Marijo Roiko, PhD, microbiology program director for pathology and laboratory services at Altru Health System in Grand Forks, N.D., said in an interview.
Dr. Roiko and colleagues compared 33 patients diagnosed and treated prior to the strategy with 33 others following its implementation. A total of 13 patients, or 39% of each cohort, developed potentially fatal methicillin-resistant S. aureus (MRSA) bacteremia. Patients’ average age ranged from 60 to 64 years, and about two-thirds of each group were men.
The investigators reported that 30-day all-cause mortality decreased from 15.6% to 13.3% after the protocol. In addition, 30-day readmission rates decreased from 25% to 11% of the group diagnosed and managed with the new strategy. Dr. Roiko presented these and other findings from the chart review at the annual meeting of the American Society for Microbiology.
Overall, the average length of stay decreased from 13 days to 10 days among the patients with S. aureus bacteremia. Among the subgroup of patients with MRSA, the length of stay dropped from 15 to 12 days. Among those with methicillin-susceptible S. aureus infections, 11 days decreased to 9 days after institution of the protocol.
The researchers also looked at time to antibiotic deescalation, and the average time decreased from 3 days to 1 day with the new strategy.
“These results demonstrate the utility of rapid testing from positive blood cultures and antibiotic stewardship for patients with Staph. aureus bacteremia,” Dr. Roiko said.
In terms of return on investment, the estimated cost savings associated with the 3-day reduction in length of hospital stay was sufficient to cover the increased capital expenditures and reagent costs, the researchers found. They estimated these increased costs as $78,960, excluding ICU and ancillary charges. The approximate $4,290 saved per day multiplied by 33 patients means the new protocol saved a total of $141,570.
Traditionally, patients with a positive blood culture of S. aureus had a gram stain, followed by provider notification when positive. Targeted antibiotic therapy was either administered at this point or held for culture-based identification and susceptibility testing. In the new protocol, a rapid culture identification panel (FilmArray BCID) is added at the time of gram staining. Positive results are reported to both the provider and pharmacist. Targeted therapy is then either administered or held based on culture-based susceptibility testing (species identification is determined as needed).
The current study findings add to a literature already supporting use of rapid blood cultures and/or stewardship guidance to address S. aureus bacteremia in academic and tertiary care centers (J Clin Microbiol. 2016;54:2455-63; Clin Microbiol Infect. 2015;21:313-22, and Clin. Infect. Dis. 2015;61:1071-80.
Dr. Roiko had no relevant financial disclosures.
NEW ORLEANS – Community hospitals could see positive outcomes using a Staphylococcus aureus bacteremia strategy that combines rapid blood cultures to speed diagnosis with antibiotic stewardship to guide treatment.
Many academic medical centers report improved outcomes with this approach. Now a study of 66 patients at a medium-sized hospital in rural North Dakota suggests this strategy translates well to the community hospital setting and can reduce mortality and 30-day readmission rates, and increase cost-effectiveness overall.
“I was pleased to see we were able to replicate the positive outcomes observed in studies from large tertiary care centers with our small cohort,” Marijo Roiko, PhD, microbiology program director for pathology and laboratory services at Altru Health System in Grand Forks, N.D., said in an interview.
Dr. Roiko and colleagues compared 33 patients diagnosed and treated prior to the strategy with 33 others following its implementation. A total of 13 patients, or 39% of each cohort, developed potentially fatal methicillin-resistant S. aureus (MRSA) bacteremia. Patients’ average age ranged from 60 to 64 years, and about two-thirds of each group were men.
The investigators reported that 30-day all-cause mortality decreased from 15.6% to 13.3% after the protocol. In addition, 30-day readmission rates decreased from 25% to 11% of the group diagnosed and managed with the new strategy. Dr. Roiko presented these and other findings from the chart review at the annual meeting of the American Society for Microbiology.
Overall, the average length of stay decreased from 13 days to 10 days among the patients with S. aureus bacteremia. Among the subgroup of patients with MRSA, the length of stay dropped from 15 to 12 days. Among those with methicillin-susceptible S. aureus infections, 11 days decreased to 9 days after institution of the protocol.
The researchers also looked at time to antibiotic deescalation, and the average time decreased from 3 days to 1 day with the new strategy.
“These results demonstrate the utility of rapid testing from positive blood cultures and antibiotic stewardship for patients with Staph. aureus bacteremia,” Dr. Roiko said.
In terms of return on investment, the estimated cost savings associated with the 3-day reduction in length of hospital stay was sufficient to cover the increased capital expenditures and reagent costs, the researchers found. They estimated these increased costs as $78,960, excluding ICU and ancillary charges. The approximate $4,290 saved per day multiplied by 33 patients means the new protocol saved a total of $141,570.
Traditionally, patients with a positive blood culture of S. aureus had a gram stain, followed by provider notification when positive. Targeted antibiotic therapy was either administered at this point or held for culture-based identification and susceptibility testing. In the new protocol, a rapid culture identification panel (FilmArray BCID) is added at the time of gram staining. Positive results are reported to both the provider and pharmacist. Targeted therapy is then either administered or held based on culture-based susceptibility testing (species identification is determined as needed).
The current study findings add to a literature already supporting use of rapid blood cultures and/or stewardship guidance to address S. aureus bacteremia in academic and tertiary care centers (J Clin Microbiol. 2016;54:2455-63; Clin Microbiol Infect. 2015;21:313-22, and Clin. Infect. Dis. 2015;61:1071-80.
Dr. Roiko had no relevant financial disclosures.
NEW ORLEANS – Community hospitals could see positive outcomes using a Staphylococcus aureus bacteremia strategy that combines rapid blood cultures to speed diagnosis with antibiotic stewardship to guide treatment.
Many academic medical centers report improved outcomes with this approach. Now a study of 66 patients at a medium-sized hospital in rural North Dakota suggests this strategy translates well to the community hospital setting and can reduce mortality and 30-day readmission rates, and increase cost-effectiveness overall.
“I was pleased to see we were able to replicate the positive outcomes observed in studies from large tertiary care centers with our small cohort,” Marijo Roiko, PhD, microbiology program director for pathology and laboratory services at Altru Health System in Grand Forks, N.D., said in an interview.
Dr. Roiko and colleagues compared 33 patients diagnosed and treated prior to the strategy with 33 others following its implementation. A total of 13 patients, or 39% of each cohort, developed potentially fatal methicillin-resistant S. aureus (MRSA) bacteremia. Patients’ average age ranged from 60 to 64 years, and about two-thirds of each group were men.
The investigators reported that 30-day all-cause mortality decreased from 15.6% to 13.3% after the protocol. In addition, 30-day readmission rates decreased from 25% to 11% of the group diagnosed and managed with the new strategy. Dr. Roiko presented these and other findings from the chart review at the annual meeting of the American Society for Microbiology.
Overall, the average length of stay decreased from 13 days to 10 days among the patients with S. aureus bacteremia. Among the subgroup of patients with MRSA, the length of stay dropped from 15 to 12 days. Among those with methicillin-susceptible S. aureus infections, 11 days decreased to 9 days after institution of the protocol.
The researchers also looked at time to antibiotic deescalation, and the average time decreased from 3 days to 1 day with the new strategy.
“These results demonstrate the utility of rapid testing from positive blood cultures and antibiotic stewardship for patients with Staph. aureus bacteremia,” Dr. Roiko said.
In terms of return on investment, the estimated cost savings associated with the 3-day reduction in length of hospital stay was sufficient to cover the increased capital expenditures and reagent costs, the researchers found. They estimated these increased costs as $78,960, excluding ICU and ancillary charges. The approximate $4,290 saved per day multiplied by 33 patients means the new protocol saved a total of $141,570.
Traditionally, patients with a positive blood culture of S. aureus had a gram stain, followed by provider notification when positive. Targeted antibiotic therapy was either administered at this point or held for culture-based identification and susceptibility testing. In the new protocol, a rapid culture identification panel (FilmArray BCID) is added at the time of gram staining. Positive results are reported to both the provider and pharmacist. Targeted therapy is then either administered or held based on culture-based susceptibility testing (species identification is determined as needed).
The current study findings add to a literature already supporting use of rapid blood cultures and/or stewardship guidance to address S. aureus bacteremia in academic and tertiary care centers (J Clin Microbiol. 2016;54:2455-63; Clin Microbiol Infect. 2015;21:313-22, and Clin. Infect. Dis. 2015;61:1071-80.
Dr. Roiko had no relevant financial disclosures.
AT ASM MICROBE 2017
Key clinical point:
Major finding: 30-day mortality dropped from 15.6% prior to the protocol to 13.3% after implementation.
Data source: A retrospective comparison of 33 patients receiving traditional diagnosis and management versus 33 others with a new rapid blood culture and stewardship program approach.
Disclosures: Dr. Roiko had no relevant financial disclosures.
Routine blood glucose monitoring does not improve control or QOL
Self-monitoring of blood glucose in patients with non–insulin-treated type 2 diabetes mellitus (T2DM) does not appear to make any difference to blood glucose control or quality of life, a new study has found.
The researchers report the results of the Monitor Trial in which 418 patients with non–insulin-treated T2DM were randomized either to once-daily self-monitoring of blood glucose with automatic tailored messages, once-daily monitoring with no messages, and no monitoring. Their report appears in the June 10 online edition of JAMA Internal Medicine, timed to appear simultaneously with the data’s presentation at the annual meeting of the American Diabetes Association
2017.1233).
Researchers also saw no significant differences in rates of insulin initiation, the incidence of hypoglycemia, or health care utilization.
“This null result occurred despite training participants and primary care clinicians on the use and interpretation of the meter results,” wrote Laura A. Young, MD, of the University of North Carolina at Chapel Hill.
While the findings reflect data from earlier studies suggesting limited usefulness of self-monitoring of blood glucose in these patients, the authors commented that self-monitoring has persisted as a cornerstone of clinical management of non–insulin-treated T2DM.
“As the first large pragmatic U.S. trial of SMBG [self-monitoring of blood glucose], our findings provide evidence to guide patients and clinicians making important clinical decisions about routine blood glucose monitoring,” they wrote. “Based on these findings, patients and clinicians should engage in dialogue regarding SMBG with the current evidence suggesting that SMBG should not be routine for most patients with non– insulin-treated T2DM.”
The main difference seen between the three groups was in the Summary of Diabetes Self-Care Activities, which the authors said reflected the intervention itself.
Patients taking a GLP-1 agonist at baseline were significantly more likely to increase their dose of the drug if they were in one of the self-monitoring groups, compared with the no-monitoring group, but the authors noted that the numbers were small.
Researchers also saw that African Americans in the self-monitoring with messaging group had significantly lower health-related quality of life scores, compared with the no-monitoring group, although this difference was not seen with the self-monitoring without messaging.
The participants in the trial, which was conducted at 15 primary care practices in central North Carolina, were all older than 30 years and had HbA1c levels between 6.5% and 9.5% in the 6 months before screening.
Compliance rates were similar between the two self-monitoring groups and declined at a similar rate.
The authors cautioned that their study was not powered to examine the effectiveness of self-monitoring versus no monitoring in certain clinical situations, such as the initiation of a new medication or a change in medication dose.
“Proponents of routine SMBG have cited evidence that this testing approach is useful for patients with newly diagnosed diabetes or patients with poorer glycemic control,” they said.” Although disease duration, experience using SMBG, baseline glycemic control, antihyperglycemic treatment, age, race, health literacy, and number of comorbidities made no discernible difference in glycemic control at 52 weeks, absence of evidence is not evidence of absence.”
They also commented on the potential influence of more tailored interventions such as the messaging, saying that while earlier smaller studies had suggested this could be of benefit, this was not shown in their study.
The study was supported by a Patient-Centered Outcomes Research Institute Award and the National Center for Advancing Translational Sciences, National Institutes of Health. Two authors declared grants and nonfinancial support from a range of pharmaceutical companies, and the University of North Carolina licensed its interest in copyright works to Telcare for a glucose messaging and treatment algorithm for the purposes of commercialization.
In most care settings, the statement “you have diabetes” still triggers prescription of a glucometer and instruction on how to perform self-monitoring of blood glucose. Every 3 months thereafter, patients’ glucose logs are reviewed and routine self-monitoring of blood glucose is encouraged, regardless of patients’ risk of hypoglycemia or severe hyperglycemia, because common sense tells us that patients who proactively manage and monitor their diabetes should achieve better outcomes.
The surprising finding of this study make us question the current seemingly common sense–based strategy to encourage routine self-monitoring of blood glucose, and support the Choosing Wisely recommendations of the Society of General Internal Medicine and Endocrine Society that discourage frequent blood glucose monitoring among patients with type 2 diabetes. Routine self-monitoring of blood glucose merits a “less is more” designation because there were no clear benefits accrued, which leaves only possible harms.
Elaine C. Khoong, MD, is from the department of medicine, University of California, San Francisco, and Joseph S. Ross, MD, is from the section of general internal medicine, Yale University School of Medicine and associate editor of JAMA Internal Medicine. These comments are adapted from an accompanying editorial (JAMA Intern Med. 2017. Jun 10. doi: 10.1001/jamainternmed.2017.1233 ). Dr. Ross receives research funding through Yale University from Medtronic and the Food and Drug Administration, from Johnson & Johnson, the Centers for Medicare and Medicaid Services, the Blue Cross Blue Shield Association, and from the Laura and John Arnold Foundation. No other disclosures were declared.
In most care settings, the statement “you have diabetes” still triggers prescription of a glucometer and instruction on how to perform self-monitoring of blood glucose. Every 3 months thereafter, patients’ glucose logs are reviewed and routine self-monitoring of blood glucose is encouraged, regardless of patients’ risk of hypoglycemia or severe hyperglycemia, because common sense tells us that patients who proactively manage and monitor their diabetes should achieve better outcomes.
The surprising finding of this study make us question the current seemingly common sense–based strategy to encourage routine self-monitoring of blood glucose, and support the Choosing Wisely recommendations of the Society of General Internal Medicine and Endocrine Society that discourage frequent blood glucose monitoring among patients with type 2 diabetes. Routine self-monitoring of blood glucose merits a “less is more” designation because there were no clear benefits accrued, which leaves only possible harms.
Elaine C. Khoong, MD, is from the department of medicine, University of California, San Francisco, and Joseph S. Ross, MD, is from the section of general internal medicine, Yale University School of Medicine and associate editor of JAMA Internal Medicine. These comments are adapted from an accompanying editorial (JAMA Intern Med. 2017. Jun 10. doi: 10.1001/jamainternmed.2017.1233 ). Dr. Ross receives research funding through Yale University from Medtronic and the Food and Drug Administration, from Johnson & Johnson, the Centers for Medicare and Medicaid Services, the Blue Cross Blue Shield Association, and from the Laura and John Arnold Foundation. No other disclosures were declared.
In most care settings, the statement “you have diabetes” still triggers prescription of a glucometer and instruction on how to perform self-monitoring of blood glucose. Every 3 months thereafter, patients’ glucose logs are reviewed and routine self-monitoring of blood glucose is encouraged, regardless of patients’ risk of hypoglycemia or severe hyperglycemia, because common sense tells us that patients who proactively manage and monitor their diabetes should achieve better outcomes.
The surprising finding of this study make us question the current seemingly common sense–based strategy to encourage routine self-monitoring of blood glucose, and support the Choosing Wisely recommendations of the Society of General Internal Medicine and Endocrine Society that discourage frequent blood glucose monitoring among patients with type 2 diabetes. Routine self-monitoring of blood glucose merits a “less is more” designation because there were no clear benefits accrued, which leaves only possible harms.
Elaine C. Khoong, MD, is from the department of medicine, University of California, San Francisco, and Joseph S. Ross, MD, is from the section of general internal medicine, Yale University School of Medicine and associate editor of JAMA Internal Medicine. These comments are adapted from an accompanying editorial (JAMA Intern Med. 2017. Jun 10. doi: 10.1001/jamainternmed.2017.1233 ). Dr. Ross receives research funding through Yale University from Medtronic and the Food and Drug Administration, from Johnson & Johnson, the Centers for Medicare and Medicaid Services, the Blue Cross Blue Shield Association, and from the Laura and John Arnold Foundation. No other disclosures were declared.
Self-monitoring of blood glucose in patients with non–insulin-treated type 2 diabetes mellitus (T2DM) does not appear to make any difference to blood glucose control or quality of life, a new study has found.
The researchers report the results of the Monitor Trial in which 418 patients with non–insulin-treated T2DM were randomized either to once-daily self-monitoring of blood glucose with automatic tailored messages, once-daily monitoring with no messages, and no monitoring. Their report appears in the June 10 online edition of JAMA Internal Medicine, timed to appear simultaneously with the data’s presentation at the annual meeting of the American Diabetes Association
2017.1233).
Researchers also saw no significant differences in rates of insulin initiation, the incidence of hypoglycemia, or health care utilization.
“This null result occurred despite training participants and primary care clinicians on the use and interpretation of the meter results,” wrote Laura A. Young, MD, of the University of North Carolina at Chapel Hill.
While the findings reflect data from earlier studies suggesting limited usefulness of self-monitoring of blood glucose in these patients, the authors commented that self-monitoring has persisted as a cornerstone of clinical management of non–insulin-treated T2DM.
“As the first large pragmatic U.S. trial of SMBG [self-monitoring of blood glucose], our findings provide evidence to guide patients and clinicians making important clinical decisions about routine blood glucose monitoring,” they wrote. “Based on these findings, patients and clinicians should engage in dialogue regarding SMBG with the current evidence suggesting that SMBG should not be routine for most patients with non– insulin-treated T2DM.”
The main difference seen between the three groups was in the Summary of Diabetes Self-Care Activities, which the authors said reflected the intervention itself.
Patients taking a GLP-1 agonist at baseline were significantly more likely to increase their dose of the drug if they were in one of the self-monitoring groups, compared with the no-monitoring group, but the authors noted that the numbers were small.
Researchers also saw that African Americans in the self-monitoring with messaging group had significantly lower health-related quality of life scores, compared with the no-monitoring group, although this difference was not seen with the self-monitoring without messaging.
The participants in the trial, which was conducted at 15 primary care practices in central North Carolina, were all older than 30 years and had HbA1c levels between 6.5% and 9.5% in the 6 months before screening.
Compliance rates were similar between the two self-monitoring groups and declined at a similar rate.
The authors cautioned that their study was not powered to examine the effectiveness of self-monitoring versus no monitoring in certain clinical situations, such as the initiation of a new medication or a change in medication dose.
“Proponents of routine SMBG have cited evidence that this testing approach is useful for patients with newly diagnosed diabetes or patients with poorer glycemic control,” they said.” Although disease duration, experience using SMBG, baseline glycemic control, antihyperglycemic treatment, age, race, health literacy, and number of comorbidities made no discernible difference in glycemic control at 52 weeks, absence of evidence is not evidence of absence.”
They also commented on the potential influence of more tailored interventions such as the messaging, saying that while earlier smaller studies had suggested this could be of benefit, this was not shown in their study.
The study was supported by a Patient-Centered Outcomes Research Institute Award and the National Center for Advancing Translational Sciences, National Institutes of Health. Two authors declared grants and nonfinancial support from a range of pharmaceutical companies, and the University of North Carolina licensed its interest in copyright works to Telcare for a glucose messaging and treatment algorithm for the purposes of commercialization.
Self-monitoring of blood glucose in patients with non–insulin-treated type 2 diabetes mellitus (T2DM) does not appear to make any difference to blood glucose control or quality of life, a new study has found.
The researchers report the results of the Monitor Trial in which 418 patients with non–insulin-treated T2DM were randomized either to once-daily self-monitoring of blood glucose with automatic tailored messages, once-daily monitoring with no messages, and no monitoring. Their report appears in the June 10 online edition of JAMA Internal Medicine, timed to appear simultaneously with the data’s presentation at the annual meeting of the American Diabetes Association
2017.1233).
Researchers also saw no significant differences in rates of insulin initiation, the incidence of hypoglycemia, or health care utilization.
“This null result occurred despite training participants and primary care clinicians on the use and interpretation of the meter results,” wrote Laura A. Young, MD, of the University of North Carolina at Chapel Hill.
While the findings reflect data from earlier studies suggesting limited usefulness of self-monitoring of blood glucose in these patients, the authors commented that self-monitoring has persisted as a cornerstone of clinical management of non–insulin-treated T2DM.
“As the first large pragmatic U.S. trial of SMBG [self-monitoring of blood glucose], our findings provide evidence to guide patients and clinicians making important clinical decisions about routine blood glucose monitoring,” they wrote. “Based on these findings, patients and clinicians should engage in dialogue regarding SMBG with the current evidence suggesting that SMBG should not be routine for most patients with non– insulin-treated T2DM.”
The main difference seen between the three groups was in the Summary of Diabetes Self-Care Activities, which the authors said reflected the intervention itself.
Patients taking a GLP-1 agonist at baseline were significantly more likely to increase their dose of the drug if they were in one of the self-monitoring groups, compared with the no-monitoring group, but the authors noted that the numbers were small.
Researchers also saw that African Americans in the self-monitoring with messaging group had significantly lower health-related quality of life scores, compared with the no-monitoring group, although this difference was not seen with the self-monitoring without messaging.
The participants in the trial, which was conducted at 15 primary care practices in central North Carolina, were all older than 30 years and had HbA1c levels between 6.5% and 9.5% in the 6 months before screening.
Compliance rates were similar between the two self-monitoring groups and declined at a similar rate.
The authors cautioned that their study was not powered to examine the effectiveness of self-monitoring versus no monitoring in certain clinical situations, such as the initiation of a new medication or a change in medication dose.
“Proponents of routine SMBG have cited evidence that this testing approach is useful for patients with newly diagnosed diabetes or patients with poorer glycemic control,” they said.” Although disease duration, experience using SMBG, baseline glycemic control, antihyperglycemic treatment, age, race, health literacy, and number of comorbidities made no discernible difference in glycemic control at 52 weeks, absence of evidence is not evidence of absence.”
They also commented on the potential influence of more tailored interventions such as the messaging, saying that while earlier smaller studies had suggested this could be of benefit, this was not shown in their study.
The study was supported by a Patient-Centered Outcomes Research Institute Award and the National Center for Advancing Translational Sciences, National Institutes of Health. Two authors declared grants and nonfinancial support from a range of pharmaceutical companies, and the University of North Carolina licensed its interest in copyright works to Telcare for a glucose messaging and treatment algorithm for the purposes of commercialization.
FROM JAMA INTERNAL MEDICINE
Key clinical point:
Major finding: Patients with non–insulin-treated T2DM who do not use routine self-monitoring of blood glucose show the same blood glucose control and health-related quality of life as those who do self-monitor.
Data source: A 1-year open-label randomized trial in 418 patients with T2DM.
Disclosures: The study was supported by a Patient-Centered Outcomes Research Institute Award and the National Center for Advancing Translational Sciences, National Institutes of Health. Two authors declared grants and nonfinancial support from a range of pharmaceutical companies, and the University of North Carolina licensed its interest in copyright works to Telcare for a glucose messaging and treatment algorithm for the purposes of commercialization.
When fecal transplants for C. diff. fail, try, try again
CHICAGO – The best remedy for a failed fecal microbiota transplant for recurrent Clostridium difficile infection is most likely a second – or even a third or fourth attempt, according to Monika Fischer, MD.
Fecal microbiota transplants (FMTs) cure the large majority of those with recurrent C. difficile. But for those who don’t respond or who have an early recurrence, repeating the procedure will almost always effect cure, she said at the annual Digestive Disease Week.
“My recommendation would be to repeat FMT once you make sure the diagnosis actually is recurrent C. difficile,” said Dr. Fischer of Indiana University, Indianapolis. “There are sufficient data showing that the success rate after two FMTs significantly increases independent of the delivery route. But the effectiveness rate is highest when FMT is delivered via colonoscopy, so I recommend the second FMT be delivered that way.”
Recurrent failures can also be a sign that something else is amiss clinically, she said. So before proceeding with multiple procedures, some detective work may be in order. It’s best to start with confirmatory testing for the organism, she said.
“We have seen that about 25% of patients referred for FMT don’t actually have C. difficile at all,” Dr. Fischer said. “Be thinking about an alternative diagnosis when the stool tests negative, but the patient is still symptomatic, or if, before the FMT, there was less than a 50% improvement with vancomycin or fidaxomicin therapy.”
“When evaluating a patient for FMT failure, it should be confirmed by stool testing, preferably by toxin testing. Recent studies suggest that PCR [polymerase chain reaction]–positive but toxin-negative patients may be colonized with C. difficile but that an alternative pathology is driving the symptoms. Toxin-negative patients’ outcome is similar with or without treatment, and it is very rare that toxin-negative patients develop CDI [C. difficile infection]–related complications.”
For these patients, the problem could be any of the conditions that cause chronic diarrhea: inflammatory bowel disease, irritable bowel syndrome, celiac disease, microscopic colitis, bile salt malabsorption, chronic pancreatitis, or some other kind of infection. If C. difficile is the confirmed etiology, repeated FMTs are the way to go, Dr. Fischer said.
However, it may be worth mixing up the delivery method. The ever-expanding data on FMT continue to show that colonoscopy delivery has the lowest failure rate – about 10%. Enema is the least successful, with a 40% failure rate. In between those are nasoduodenal tube delivery, which is associated with a 20% failure rate, and oral capsules, with a failure rate varying from 12% to 30%. Fresh stool is also more effective than frozen, which, in turn, is more effective than the lyophilized preparation, Dr. Fischer said.
“Options are to repeat FMT via colonoscopy, but for patients who have had several failures, consider using the upper and lower route at the same time, and give fresh stool, especially if the first transplants used frozen.”
Although the efficacy of FMT doesn’t appear to depend on donor characteristics, patient characteristics do seem to play a role. Dr. Fischer and her colleagues have created an assessment tool to predict who may be at risk for failure. The model was developed in a 300-patient FMT cohort at two centers and validated in a third academic center FMT population. Of 24 clinical variables, three were incorporated into the failure risk model: severe disease (odds ratio, 6), inpatient status (OR, 3.8), and the number of prior C. difficile–related hospitalizations (OR, 1.4 for each one). For severe disease, patients got 5 points on the scale; for inpatient status, 4 points; and for each prior hospitalization, 1 point.
“Patients in the low-risk category [0] had up to 5% chance of failing. Patients with intermediate risk [1-2] had a 15% chance of failing, and patients in the high-risk category [3 or more points] had higher than 35% chance of not responding to single FMT,” Dr. Fischer said.
She also examined this tool in an extended cohort of nearly 500 patients at four additional sites; about 5% had failed more than two FMTs. “We identified two additional risk factors for failing multiple transplants,” Dr. Fischer said. “These were immunocompromised state, which increased the risk by 4 times, and male gender, which increased the risk by 2.5 times.”
She offered some options for the rare patient who has failed repeat FMTs and doesn’t want to try again. “There are some alternative or adjunctive therapies to repeat FMTs that may be considered, in lieu of repeating FMT for the third or fourth time or even following the first FMT failure, if dictated by patient preference. We sometimes offer these for elderly or frail patients or those with a limited life expectancy. These therapy options are from small, nonrandomized trials in multiply recurrent C. difficile infections but have not been vetted in the FMT nonresponder population.”
These include a vancomycin taper, or a vancomycin taper followed by fidaxomicin. Another option, albeit with limited applicability, is suppressive low-dose vancomycin 125 mg given every day, every other day, or every third day, indefinitely. “This can be especially good for elderly, frail patients with limited life expectancy, needing ongoing antibiotic therapy for urinary tract infections,” she said.
Finally, an 8-week vancomycin taper with daily kefir ingestion has been helpful for some patients. Although probiotics have never been proven helpful in C. difficile infections or FMT success, kefir is a different sort of supplement, she said.
“Kefir is different from yogurt. It contains bacteriocins like nisin, a protein with antibacterial properties produced by Lactococcus lactis.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – The best remedy for a failed fecal microbiota transplant for recurrent Clostridium difficile infection is most likely a second – or even a third or fourth attempt, according to Monika Fischer, MD.
Fecal microbiota transplants (FMTs) cure the large majority of those with recurrent C. difficile. But for those who don’t respond or who have an early recurrence, repeating the procedure will almost always effect cure, she said at the annual Digestive Disease Week.
“My recommendation would be to repeat FMT once you make sure the diagnosis actually is recurrent C. difficile,” said Dr. Fischer of Indiana University, Indianapolis. “There are sufficient data showing that the success rate after two FMTs significantly increases independent of the delivery route. But the effectiveness rate is highest when FMT is delivered via colonoscopy, so I recommend the second FMT be delivered that way.”
Recurrent failures can also be a sign that something else is amiss clinically, she said. So before proceeding with multiple procedures, some detective work may be in order. It’s best to start with confirmatory testing for the organism, she said.
“We have seen that about 25% of patients referred for FMT don’t actually have C. difficile at all,” Dr. Fischer said. “Be thinking about an alternative diagnosis when the stool tests negative, but the patient is still symptomatic, or if, before the FMT, there was less than a 50% improvement with vancomycin or fidaxomicin therapy.”
“When evaluating a patient for FMT failure, it should be confirmed by stool testing, preferably by toxin testing. Recent studies suggest that PCR [polymerase chain reaction]–positive but toxin-negative patients may be colonized with C. difficile but that an alternative pathology is driving the symptoms. Toxin-negative patients’ outcome is similar with or without treatment, and it is very rare that toxin-negative patients develop CDI [C. difficile infection]–related complications.”
For these patients, the problem could be any of the conditions that cause chronic diarrhea: inflammatory bowel disease, irritable bowel syndrome, celiac disease, microscopic colitis, bile salt malabsorption, chronic pancreatitis, or some other kind of infection. If C. difficile is the confirmed etiology, repeated FMTs are the way to go, Dr. Fischer said.
However, it may be worth mixing up the delivery method. The ever-expanding data on FMT continue to show that colonoscopy delivery has the lowest failure rate – about 10%. Enema is the least successful, with a 40% failure rate. In between those are nasoduodenal tube delivery, which is associated with a 20% failure rate, and oral capsules, with a failure rate varying from 12% to 30%. Fresh stool is also more effective than frozen, which, in turn, is more effective than the lyophilized preparation, Dr. Fischer said.
“Options are to repeat FMT via colonoscopy, but for patients who have had several failures, consider using the upper and lower route at the same time, and give fresh stool, especially if the first transplants used frozen.”
Although the efficacy of FMT doesn’t appear to depend on donor characteristics, patient characteristics do seem to play a role. Dr. Fischer and her colleagues have created an assessment tool to predict who may be at risk for failure. The model was developed in a 300-patient FMT cohort at two centers and validated in a third academic center FMT population. Of 24 clinical variables, three were incorporated into the failure risk model: severe disease (odds ratio, 6), inpatient status (OR, 3.8), and the number of prior C. difficile–related hospitalizations (OR, 1.4 for each one). For severe disease, patients got 5 points on the scale; for inpatient status, 4 points; and for each prior hospitalization, 1 point.
“Patients in the low-risk category [0] had up to 5% chance of failing. Patients with intermediate risk [1-2] had a 15% chance of failing, and patients in the high-risk category [3 or more points] had higher than 35% chance of not responding to single FMT,” Dr. Fischer said.
She also examined this tool in an extended cohort of nearly 500 patients at four additional sites; about 5% had failed more than two FMTs. “We identified two additional risk factors for failing multiple transplants,” Dr. Fischer said. “These were immunocompromised state, which increased the risk by 4 times, and male gender, which increased the risk by 2.5 times.”
She offered some options for the rare patient who has failed repeat FMTs and doesn’t want to try again. “There are some alternative or adjunctive therapies to repeat FMTs that may be considered, in lieu of repeating FMT for the third or fourth time or even following the first FMT failure, if dictated by patient preference. We sometimes offer these for elderly or frail patients or those with a limited life expectancy. These therapy options are from small, nonrandomized trials in multiply recurrent C. difficile infections but have not been vetted in the FMT nonresponder population.”
These include a vancomycin taper, or a vancomycin taper followed by fidaxomicin. Another option, albeit with limited applicability, is suppressive low-dose vancomycin 125 mg given every day, every other day, or every third day, indefinitely. “This can be especially good for elderly, frail patients with limited life expectancy, needing ongoing antibiotic therapy for urinary tract infections,” she said.
Finally, an 8-week vancomycin taper with daily kefir ingestion has been helpful for some patients. Although probiotics have never been proven helpful in C. difficile infections or FMT success, kefir is a different sort of supplement, she said.
“Kefir is different from yogurt. It contains bacteriocins like nisin, a protein with antibacterial properties produced by Lactococcus lactis.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – The best remedy for a failed fecal microbiota transplant for recurrent Clostridium difficile infection is most likely a second – or even a third or fourth attempt, according to Monika Fischer, MD.
Fecal microbiota transplants (FMTs) cure the large majority of those with recurrent C. difficile. But for those who don’t respond or who have an early recurrence, repeating the procedure will almost always effect cure, she said at the annual Digestive Disease Week.
“My recommendation would be to repeat FMT once you make sure the diagnosis actually is recurrent C. difficile,” said Dr. Fischer of Indiana University, Indianapolis. “There are sufficient data showing that the success rate after two FMTs significantly increases independent of the delivery route. But the effectiveness rate is highest when FMT is delivered via colonoscopy, so I recommend the second FMT be delivered that way.”
Recurrent failures can also be a sign that something else is amiss clinically, she said. So before proceeding with multiple procedures, some detective work may be in order. It’s best to start with confirmatory testing for the organism, she said.
“We have seen that about 25% of patients referred for FMT don’t actually have C. difficile at all,” Dr. Fischer said. “Be thinking about an alternative diagnosis when the stool tests negative, but the patient is still symptomatic, or if, before the FMT, there was less than a 50% improvement with vancomycin or fidaxomicin therapy.”
“When evaluating a patient for FMT failure, it should be confirmed by stool testing, preferably by toxin testing. Recent studies suggest that PCR [polymerase chain reaction]–positive but toxin-negative patients may be colonized with C. difficile but that an alternative pathology is driving the symptoms. Toxin-negative patients’ outcome is similar with or without treatment, and it is very rare that toxin-negative patients develop CDI [C. difficile infection]–related complications.”
For these patients, the problem could be any of the conditions that cause chronic diarrhea: inflammatory bowel disease, irritable bowel syndrome, celiac disease, microscopic colitis, bile salt malabsorption, chronic pancreatitis, or some other kind of infection. If C. difficile is the confirmed etiology, repeated FMTs are the way to go, Dr. Fischer said.
However, it may be worth mixing up the delivery method. The ever-expanding data on FMT continue to show that colonoscopy delivery has the lowest failure rate – about 10%. Enema is the least successful, with a 40% failure rate. In between those are nasoduodenal tube delivery, which is associated with a 20% failure rate, and oral capsules, with a failure rate varying from 12% to 30%. Fresh stool is also more effective than frozen, which, in turn, is more effective than the lyophilized preparation, Dr. Fischer said.
“Options are to repeat FMT via colonoscopy, but for patients who have had several failures, consider using the upper and lower route at the same time, and give fresh stool, especially if the first transplants used frozen.”
Although the efficacy of FMT doesn’t appear to depend on donor characteristics, patient characteristics do seem to play a role. Dr. Fischer and her colleagues have created an assessment tool to predict who may be at risk for failure. The model was developed in a 300-patient FMT cohort at two centers and validated in a third academic center FMT population. Of 24 clinical variables, three were incorporated into the failure risk model: severe disease (odds ratio, 6), inpatient status (OR, 3.8), and the number of prior C. difficile–related hospitalizations (OR, 1.4 for each one). For severe disease, patients got 5 points on the scale; for inpatient status, 4 points; and for each prior hospitalization, 1 point.
“Patients in the low-risk category [0] had up to 5% chance of failing. Patients with intermediate risk [1-2] had a 15% chance of failing, and patients in the high-risk category [3 or more points] had higher than 35% chance of not responding to single FMT,” Dr. Fischer said.
She also examined this tool in an extended cohort of nearly 500 patients at four additional sites; about 5% had failed more than two FMTs. “We identified two additional risk factors for failing multiple transplants,” Dr. Fischer said. “These were immunocompromised state, which increased the risk by 4 times, and male gender, which increased the risk by 2.5 times.”
She offered some options for the rare patient who has failed repeat FMTs and doesn’t want to try again. “There are some alternative or adjunctive therapies to repeat FMTs that may be considered, in lieu of repeating FMT for the third or fourth time or even following the first FMT failure, if dictated by patient preference. We sometimes offer these for elderly or frail patients or those with a limited life expectancy. These therapy options are from small, nonrandomized trials in multiply recurrent C. difficile infections but have not been vetted in the FMT nonresponder population.”
These include a vancomycin taper, or a vancomycin taper followed by fidaxomicin. Another option, albeit with limited applicability, is suppressive low-dose vancomycin 125 mg given every day, every other day, or every third day, indefinitely. “This can be especially good for elderly, frail patients with limited life expectancy, needing ongoing antibiotic therapy for urinary tract infections,” she said.
Finally, an 8-week vancomycin taper with daily kefir ingestion has been helpful for some patients. Although probiotics have never been proven helpful in C. difficile infections or FMT success, kefir is a different sort of supplement, she said.
“Kefir is different from yogurt. It contains bacteriocins like nisin, a protein with antibacterial properties produced by Lactococcus lactis.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW 2017