NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW YORK - In patients with atrial fibrillation (AF) and a wide range of renal function, compared to warfarin, treatment with apixaban reduces the risk of cardiovascular events, according to multinational investigators.

As Dr. Ziad Hijazi told Reuters Health by email, "Renal dysfunction is a complex issue in patients with atrial fibrillation when balancing the risk of stroke versus the risk of bleeding."

"This study," he added, "shows that apixaban, compared with warfarin, was associated with a lower risk of stroke, death, and major bleeding, regardless of changes in renal function over time. These findings may aid clinicians in the treatment decision."

In a June 15 online paper in JAMA Cardiology, Dr. Hijazi, of Uppsala University Hospital, Sweden, and colleagues report that they came to this conclusion after examining data from a clinical trial (ARISTOTLE) on more than 16,800 AF patients randomized to apixaban or warfarin.

Over the course of a year, about a quarter (26%) maintained good renal function. Renal function declined in the others, and 13.6% showed a drop of more than 20%. The decline in renal function was more rapid in patients who were older or had comorbidities.

Overall, the risks of stroke or systemic embolism, major bleeding, and mortality were greater in patients with worsening renal function (hazard ratio, 1.53 for stroke or systemic embolism, 1.56 for major bleeding, and 2.31 for mortality).

However, such patients on apixaban, compared with warfarin, consistently demonstrated a lower relative risk of stroke or systemic embolism (HR 0.80), ischemic or unspecified stroke (HR 0.88), and major bleeding (HR 0.76).

In fact, as well as showing benefit in this group of patients, the researchers conclude, "The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function."

Commenting on the findings by email, cardiologist Dr. Anil Pandit of Scottsdale, Arizona, told Reuters Health, "The study by Hijazi et al answers very important clinical questions regarding safety and efficacy of apixaban in situations of declining renal function, a common phenomenon in a real world scenario."

An earlier meta-analysis, in which Dr. Pandit was involved, found decreased risk of major bleeding with apixaban in mild to moderate renal impairment when compared with other anticoagulants (warfarin, aspirin, and Lovenox) as a group.

"The main criticism of the findings of our meta-analysis was inapplicability in the real world scenario, where subclinical episodes of acute kidney injury and worsening renal failure, may lead to increased anticoagulant effect and bleeding," Dr. Pandit said. This new study "exactly answers this question in a large patient population, providing sustained evidence that apixaban is safe and effective in mild to moderate renal impairment patients."

"However," Dr. Pandit concluded, "one should keep in mind limitations of the retrospective data." He also pointed out that "the efficacy and safety of apixaban is not established in patients with severe renal failure, ... as this group of patients was not studied in the ARISTOTLE trial."

Bristol Myers Squibb and Pfizer funded the ARISTOTLE trial. Ten coauthors reported disclosures.

SOURCE: http://bit.ly/28LbKlt JAMA Cardiol 2016.

NEW YORK - In patients with atrial fibrillation (AF) and a wide range of renal function, compared to warfarin, treatment with apixaban reduces the risk of cardiovascular events, according to multinational investigators.

As Dr. Ziad Hijazi told Reuters Health by email, "Renal dysfunction is a complex issue in patients with atrial fibrillation when balancing the risk of stroke versus the risk of bleeding."

"This study," he added, "shows that apixaban, compared with warfarin, was associated with a lower risk of stroke, death, and major bleeding, regardless of changes in renal function over time. These findings may aid clinicians in the treatment decision."

In a June 15 online paper in JAMA Cardiology, Dr. Hijazi, of Uppsala University Hospital, Sweden, and colleagues report that they came to this conclusion after examining data from a clinical trial (ARISTOTLE) on more than 16,800 AF patients randomized to apixaban or warfarin.

Over the course of a year, about a quarter (26%) maintained good renal function. Renal function declined in the others, and 13.6% showed a drop of more than 20%. The decline in renal function was more rapid in patients who were older or had comorbidities.

Overall, the risks of stroke or systemic embolism, major bleeding, and mortality were greater in patients with worsening renal function (hazard ratio, 1.53 for stroke or systemic embolism, 1.56 for major bleeding, and 2.31 for mortality).

However, such patients on apixaban, compared with warfarin, consistently demonstrated a lower relative risk of stroke or systemic embolism (HR 0.80), ischemic or unspecified stroke (HR 0.88), and major bleeding (HR 0.76).

In fact, as well as showing benefit in this group of patients, the researchers conclude, "The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function."

Commenting on the findings by email, cardiologist Dr. Anil Pandit of Scottsdale, Arizona, told Reuters Health, "The study by Hijazi et al answers very important clinical questions regarding safety and efficacy of apixaban in situations of declining renal function, a common phenomenon in a real world scenario."

An earlier meta-analysis, in which Dr. Pandit was involved, found decreased risk of major bleeding with apixaban in mild to moderate renal impairment when compared with other anticoagulants (warfarin, aspirin, and Lovenox) as a group.

"The main criticism of the findings of our meta-analysis was inapplicability in the real world scenario, where subclinical episodes of acute kidney injury and worsening renal failure, may lead to increased anticoagulant effect and bleeding," Dr. Pandit said. This new study "exactly answers this question in a large patient population, providing sustained evidence that apixaban is safe and effective in mild to moderate renal impairment patients."

"However," Dr. Pandit concluded, "one should keep in mind limitations of the retrospective data." He also pointed out that "the efficacy and safety of apixaban is not established in patients with severe renal failure, ... as this group of patients was not studied in the ARISTOTLE trial."

Bristol Myers Squibb and Pfizer funded the ARISTOTLE trial. Ten coauthors reported disclosures.

SOURCE: http://bit.ly/28LbKlt JAMA Cardiol 2016.

NEW YORK - In patients with atrial fibrillation (AF) and a wide range of renal function, compared to warfarin, treatment with apixaban reduces the risk of cardiovascular events, according to multinational investigators.

As Dr. Ziad Hijazi told Reuters Health by email, "Renal dysfunction is a complex issue in patients with atrial fibrillation when balancing the risk of stroke versus the risk of bleeding."

"This study," he added, "shows that apixaban, compared with warfarin, was associated with a lower risk of stroke, death, and major bleeding, regardless of changes in renal function over time. These findings may aid clinicians in the treatment decision."

In a June 15 online paper in JAMA Cardiology, Dr. Hijazi, of Uppsala University Hospital, Sweden, and colleagues report that they came to this conclusion after examining data from a clinical trial (ARISTOTLE) on more than 16,800 AF patients randomized to apixaban or warfarin.

Over the course of a year, about a quarter (26%) maintained good renal function. Renal function declined in the others, and 13.6% showed a drop of more than 20%. The decline in renal function was more rapid in patients who were older or had comorbidities.

Overall, the risks of stroke or systemic embolism, major bleeding, and mortality were greater in patients with worsening renal function (hazard ratio, 1.53 for stroke or systemic embolism, 1.56 for major bleeding, and 2.31 for mortality).

However, such patients on apixaban, compared with warfarin, consistently demonstrated a lower relative risk of stroke or systemic embolism (HR 0.80), ischemic or unspecified stroke (HR 0.88), and major bleeding (HR 0.76).

In fact, as well as showing benefit in this group of patients, the researchers conclude, "The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function."

Commenting on the findings by email, cardiologist Dr. Anil Pandit of Scottsdale, Arizona, told Reuters Health, "The study by Hijazi et al answers very important clinical questions regarding safety and efficacy of apixaban in situations of declining renal function, a common phenomenon in a real world scenario."

An earlier meta-analysis, in which Dr. Pandit was involved, found decreased risk of major bleeding with apixaban in mild to moderate renal impairment when compared with other anticoagulants (warfarin, aspirin, and Lovenox) as a group.

"The main criticism of the findings of our meta-analysis was inapplicability in the real world scenario, where subclinical episodes of acute kidney injury and worsening renal failure, may lead to increased anticoagulant effect and bleeding," Dr. Pandit said. This new study "exactly answers this question in a large patient population, providing sustained evidence that apixaban is safe and effective in mild to moderate renal impairment patients."

"However," Dr. Pandit concluded, "one should keep in mind limitations of the retrospective data." He also pointed out that "the efficacy and safety of apixaban is not established in patients with severe renal failure, ... as this group of patients was not studied in the ARISTOTLE trial."

Bristol Myers Squibb and Pfizer funded the ARISTOTLE trial. Ten coauthors reported disclosures.

SOURCE: http://bit.ly/28LbKlt JAMA Cardiol 2016.

A work group for the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is leaning toward recommending a change from three to two doses of the human papillomavirus (HPV) vaccine in boys and girls aged 11-12 years.

Members of the ACIP Human Papillomavirus Work Group told the entire committee at ACIP’s June meeting that a review of all available data showed that, regardless of whether the HPV vaccine were bivalent, quadrivalent, or nine-valent, two doses were found to be noninferior, compared with three doses. A two-dose schedule, therefore, could possibly be recommended at the next ACIP meeting later this year.

©DesignPics/Thinkstock.com

The work group said it also could recommend that HPV vaccine–naive women up to age 26 years and HPV vaccine-naive men up to age 21 years also receive the vaccine. For persons who initiated but did not complete vaccination before age 15 years, or for persons who initiate the schedule after their 15th birthday – the same schedule as is currently recommended for 11- and 12-year-olds – a similar schedule is likely to be recommended again.

The recommendation for immunocompromised persons of any age would be to receive the three-dose schedule.

If these recommendations are put forth officially, the question of whether families also should be given a three-dose option will need to be decided, work group members said.

Although studies are ongoing to determine antibody persistence and long-term effectiveness after two doses, existing data indicate that waning antibody responses to HPV18 in persons vaccinated with three doses of quadrivalent HPV were not associated with loss of protection. This could mean that protective levels are actually lower than the minimum levels detected by assays, or that antibodies against other epitopes also are protective.

Predictive modeling showed that, if a two-dose schedule can provide more than 20 years of protection, over $118,000 per quality adjusted life year could be realized without sacrificing population health benefits.

The current CDC vaccination schedule for HPV in adolescents is for a three-dose series of the vaccine on a schedule of 0, 1-2, and 6 months. The same vaccination schedule is recommended for “catch-up” of previously unvaccinated adolescents aged 13-18 years.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

A work group for the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is leaning toward recommending a change from three to two doses of the human papillomavirus (HPV) vaccine in boys and girls aged 11-12 years.

Members of the ACIP Human Papillomavirus Work Group told the entire committee at ACIP’s June meeting that a review of all available data showed that, regardless of whether the HPV vaccine were bivalent, quadrivalent, or nine-valent, two doses were found to be noninferior, compared with three doses. A two-dose schedule, therefore, could possibly be recommended at the next ACIP meeting later this year.

©DesignPics/Thinkstock.com

The work group said it also could recommend that HPV vaccine–naive women up to age 26 years and HPV vaccine-naive men up to age 21 years also receive the vaccine. For persons who initiated but did not complete vaccination before age 15 years, or for persons who initiate the schedule after their 15th birthday – the same schedule as is currently recommended for 11- and 12-year-olds – a similar schedule is likely to be recommended again.

The recommendation for immunocompromised persons of any age would be to receive the three-dose schedule.

If these recommendations are put forth officially, the question of whether families also should be given a three-dose option will need to be decided, work group members said.

Although studies are ongoing to determine antibody persistence and long-term effectiveness after two doses, existing data indicate that waning antibody responses to HPV18 in persons vaccinated with three doses of quadrivalent HPV were not associated with loss of protection. This could mean that protective levels are actually lower than the minimum levels detected by assays, or that antibodies against other epitopes also are protective.

Predictive modeling showed that, if a two-dose schedule can provide more than 20 years of protection, over $118,000 per quality adjusted life year could be realized without sacrificing population health benefits.

The current CDC vaccination schedule for HPV in adolescents is for a three-dose series of the vaccine on a schedule of 0, 1-2, and 6 months. The same vaccination schedule is recommended for “catch-up” of previously unvaccinated adolescents aged 13-18 years.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

A work group for the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is leaning toward recommending a change from three to two doses of the human papillomavirus (HPV) vaccine in boys and girls aged 11-12 years.

Members of the ACIP Human Papillomavirus Work Group told the entire committee at ACIP’s June meeting that a review of all available data showed that, regardless of whether the HPV vaccine were bivalent, quadrivalent, or nine-valent, two doses were found to be noninferior, compared with three doses. A two-dose schedule, therefore, could possibly be recommended at the next ACIP meeting later this year.

©DesignPics/Thinkstock.com

The work group said it also could recommend that HPV vaccine–naive women up to age 26 years and HPV vaccine-naive men up to age 21 years also receive the vaccine. For persons who initiated but did not complete vaccination before age 15 years, or for persons who initiate the schedule after their 15th birthday – the same schedule as is currently recommended for 11- and 12-year-olds – a similar schedule is likely to be recommended again.

The recommendation for immunocompromised persons of any age would be to receive the three-dose schedule.

If these recommendations are put forth officially, the question of whether families also should be given a three-dose option will need to be decided, work group members said.

Although studies are ongoing to determine antibody persistence and long-term effectiveness after two doses, existing data indicate that waning antibody responses to HPV18 in persons vaccinated with three doses of quadrivalent HPV were not associated with loss of protection. This could mean that protective levels are actually lower than the minimum levels detected by assays, or that antibodies against other epitopes also are protective.

Predictive modeling showed that, if a two-dose schedule can provide more than 20 years of protection, over $118,000 per quality adjusted life year could be realized without sacrificing population health benefits.

The current CDC vaccination schedule for HPV in adolescents is for a three-dose series of the vaccine on a schedule of 0, 1-2, and 6 months. The same vaccination schedule is recommended for “catch-up” of previously unvaccinated adolescents aged 13-18 years.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016

Westin Boston Waterfront Hotel, Boston, MA

Program Directors

G. Alexander Patterson

David J. Sugarbaker

Program Committee

Thomas A. D’Amico

Shaf Keshavjee

James D. Luketich

Bryan F. Meyers

Scott J. Swanson

Overview

Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information: http://aats.org/focus/

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016

Westin Boston Waterfront Hotel, Boston, MA

Program Directors

G. Alexander Patterson

David J. Sugarbaker

Program Committee

Thomas A. D’Amico

Shaf Keshavjee

James D. Luketich

Bryan F. Meyers

Scott J. Swanson

Overview

Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information: http://aats.org/focus/

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016

Westin Boston Waterfront Hotel, Boston, MA

Program Directors

G. Alexander Patterson

David J. Sugarbaker

Program Committee

Thomas A. D’Amico

Shaf Keshavjee

James D. Luketich

Bryan F. Meyers

Scott J. Swanson

Overview

Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information: http://aats.org/focus/

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016
Westin Boston Waterfront Hotel
Boston, MA

Program Directors
G. Alexander Patterson
David J. Sugarbaker

Program Committee
Thomas A. D’Amico
Shaf Keshavjee
James D. Luketich
Bryan F. Meyers
Scott J. Swanson

Overview
Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016
Westin Boston Waterfront Hotel
Boston, MA

Program Directors
G. Alexander Patterson
David J. Sugarbaker

Program Committee
Thomas A. D’Amico
Shaf Keshavjee
James D. Luketich
Bryan F. Meyers
Scott J. Swanson

Overview
Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information

The preliminary program and registration information is now available for AATS Focus on Thoracic Surgery: Current and Future Challenges.

October 28-29, 2016
Westin Boston Waterfront Hotel
Boston, MA

Program Directors
G. Alexander Patterson
David J. Sugarbaker

Program Committee
Thomas A. D’Amico
Shaf Keshavjee
James D. Luketich
Bryan F. Meyers
Scott J. Swanson

Overview
Currently practicing surgeons will be able to improve patient outcomes by enriching their knowledge and technical skills in the definition, diagnosis and resolution of thoracic surgical difficulties and post-operative complications. Expert faculty will provide state-of-the-art solutions to challenges in the field. Attendees will augment their overall understanding of thoracic diseases, upgrade their competency and ability to formulate new clinical strategies, and enhance their diagnosis and surgical treatment of thoracic diseases.

More information

NEW ORLEANS – For many patients with type 1 diabetes mellitus, crossing multiple time zones by airplane upset their disease self-management. In fact, results from a new survey found that 74% reported more hyperglycemia and/or hypoglycemia while traveling overseas, and 9% avoided international travel altogether because of their disease.

“Travel has become a ubiquitous feature of modern day life. Every day around the world approximately 8 million people board an aircraft,” Benjamen E. Schoenberg said at the annual scientific sessions of the American Diabetes Association. “Based on known rates of diabetes and how often people travel, the Centers for Disease Control and Prevention and the U.S. Travel Association estimate that annually in the United States alone approximately 17 million individuals with diabetes travel for leisure, and approximately 5.6 million travel for business, and these numbers are rising by the year.”

Noting limited existing medical literature on the topic, Mr. Schoenberg of the William Sansum Diabetes Center, Santa Barbara, Calif., and his associates set out to examine the real-life experiences of individuals with type 1 diabetes traveling long-haul by airplane – defined as crossing multiple time zones. They invited members of an online community of the T1D Exchange known as Glu to complete a 45-question online survey that collected information on respondents’ diabetes history, use of technology in self-management of their diabetes, and overall travel experiences.

Of the 503 survey respondents, 71% were female, their average age was 44 years, and 75% had type 1 diabetes for longer than 10 years. The majority of respondents (81%) reported currently having a passport, and 71% reported flying long-haul at least once in the past 5 years. Nearly three-quarters of respondents (74%) experienced increased levels of hyperglycemia and/or hypoglycemia while traveling overseas, 22% ran out of insulin at some point during a trip in the past 5 years, and 9% reported avoiding international travel altogether because of problems related to diabetes management.

Mr. Schoenberg, who is an incoming first-year medical student at Thomas Jefferson University, Philadelphia, went on to report that about one in three participants indicated that their insulin “does not work the same” in flight, compared with when they’re not flying. At the same time, 5% believe that their continuous glucose monitors are less reliable in flight, and about 10% believe that their insulin pumps are less reliable in flight.

When asked what practical difficulties they faced while traveling with type 1 diabetes, the top three responses from survey participants were airport security, taking enough supplies, and crossing time zones. “Furthermore, we found that pump users experienced more difficulty with airport security than non–pump users; 42% of pump users wore their device through body scanners, and 44% reported having at least one negative experience with airport security in the past,” he said.

When asked about their greatest fear of flying long-haul, the top four responses were more hyperglycemia and/or hypoglycemia, problems with airport security, losing supplies, and glucose variability. In addition, only about 30% of respondents reported being satisfied with currently available resources intended to help people manage their disease while traveling. “There is a call to action for providers and nonprofits to continue to develop information to better suit the needs of individuals traveling with [type 1 diabetes],” Mr. Schoenberg said. “Furthermore, 55% reported that they use the Internet as their primary source and about one in four use a smart phone regularly for their self-management.”

He concluded that long-haul air travel with type 1 diabetes “is neither straightforward nor easy. Real-life experiences suggest an unmet need for personalized information. There also may be a need to evaluate insulin and devices at altitude and across time zones. Finally, the impacts of long-haul travel become more relevant as we move toward a commercial artificial pancreas system.” The researchers reported having no financial conflicts.

dbrunk@frontlinemedcom.com

NEW ORLEANS – For many patients with type 1 diabetes mellitus, crossing multiple time zones by airplane upset their disease self-management. In fact, results from a new survey found that 74% reported more hyperglycemia and/or hypoglycemia while traveling overseas, and 9% avoided international travel altogether because of their disease.

“Travel has become a ubiquitous feature of modern day life. Every day around the world approximately 8 million people board an aircraft,” Benjamen E. Schoenberg said at the annual scientific sessions of the American Diabetes Association. “Based on known rates of diabetes and how often people travel, the Centers for Disease Control and Prevention and the U.S. Travel Association estimate that annually in the United States alone approximately 17 million individuals with diabetes travel for leisure, and approximately 5.6 million travel for business, and these numbers are rising by the year.”

Noting limited existing medical literature on the topic, Mr. Schoenberg of the William Sansum Diabetes Center, Santa Barbara, Calif., and his associates set out to examine the real-life experiences of individuals with type 1 diabetes traveling long-haul by airplane – defined as crossing multiple time zones. They invited members of an online community of the T1D Exchange known as Glu to complete a 45-question online survey that collected information on respondents’ diabetes history, use of technology in self-management of their diabetes, and overall travel experiences.

Of the 503 survey respondents, 71% were female, their average age was 44 years, and 75% had type 1 diabetes for longer than 10 years. The majority of respondents (81%) reported currently having a passport, and 71% reported flying long-haul at least once in the past 5 years. Nearly three-quarters of respondents (74%) experienced increased levels of hyperglycemia and/or hypoglycemia while traveling overseas, 22% ran out of insulin at some point during a trip in the past 5 years, and 9% reported avoiding international travel altogether because of problems related to diabetes management.

Mr. Schoenberg, who is an incoming first-year medical student at Thomas Jefferson University, Philadelphia, went on to report that about one in three participants indicated that their insulin “does not work the same” in flight, compared with when they’re not flying. At the same time, 5% believe that their continuous glucose monitors are less reliable in flight, and about 10% believe that their insulin pumps are less reliable in flight.

When asked what practical difficulties they faced while traveling with type 1 diabetes, the top three responses from survey participants were airport security, taking enough supplies, and crossing time zones. “Furthermore, we found that pump users experienced more difficulty with airport security than non–pump users; 42% of pump users wore their device through body scanners, and 44% reported having at least one negative experience with airport security in the past,” he said.

When asked about their greatest fear of flying long-haul, the top four responses were more hyperglycemia and/or hypoglycemia, problems with airport security, losing supplies, and glucose variability. In addition, only about 30% of respondents reported being satisfied with currently available resources intended to help people manage their disease while traveling. “There is a call to action for providers and nonprofits to continue to develop information to better suit the needs of individuals traveling with [type 1 diabetes],” Mr. Schoenberg said. “Furthermore, 55% reported that they use the Internet as their primary source and about one in four use a smart phone regularly for their self-management.”

He concluded that long-haul air travel with type 1 diabetes “is neither straightforward nor easy. Real-life experiences suggest an unmet need for personalized information. There also may be a need to evaluate insulin and devices at altitude and across time zones. Finally, the impacts of long-haul travel become more relevant as we move toward a commercial artificial pancreas system.” The researchers reported having no financial conflicts.

dbrunk@frontlinemedcom.com

NEW ORLEANS – For many patients with type 1 diabetes mellitus, crossing multiple time zones by airplane upset their disease self-management. In fact, results from a new survey found that 74% reported more hyperglycemia and/or hypoglycemia while traveling overseas, and 9% avoided international travel altogether because of their disease.

“Travel has become a ubiquitous feature of modern day life. Every day around the world approximately 8 million people board an aircraft,” Benjamen E. Schoenberg said at the annual scientific sessions of the American Diabetes Association. “Based on known rates of diabetes and how often people travel, the Centers for Disease Control and Prevention and the U.S. Travel Association estimate that annually in the United States alone approximately 17 million individuals with diabetes travel for leisure, and approximately 5.6 million travel for business, and these numbers are rising by the year.”

Noting limited existing medical literature on the topic, Mr. Schoenberg of the William Sansum Diabetes Center, Santa Barbara, Calif., and his associates set out to examine the real-life experiences of individuals with type 1 diabetes traveling long-haul by airplane – defined as crossing multiple time zones. They invited members of an online community of the T1D Exchange known as Glu to complete a 45-question online survey that collected information on respondents’ diabetes history, use of technology in self-management of their diabetes, and overall travel experiences.

Of the 503 survey respondents, 71% were female, their average age was 44 years, and 75% had type 1 diabetes for longer than 10 years. The majority of respondents (81%) reported currently having a passport, and 71% reported flying long-haul at least once in the past 5 years. Nearly three-quarters of respondents (74%) experienced increased levels of hyperglycemia and/or hypoglycemia while traveling overseas, 22% ran out of insulin at some point during a trip in the past 5 years, and 9% reported avoiding international travel altogether because of problems related to diabetes management.

Mr. Schoenberg, who is an incoming first-year medical student at Thomas Jefferson University, Philadelphia, went on to report that about one in three participants indicated that their insulin “does not work the same” in flight, compared with when they’re not flying. At the same time, 5% believe that their continuous glucose monitors are less reliable in flight, and about 10% believe that their insulin pumps are less reliable in flight.

When asked what practical difficulties they faced while traveling with type 1 diabetes, the top three responses from survey participants were airport security, taking enough supplies, and crossing time zones. “Furthermore, we found that pump users experienced more difficulty with airport security than non–pump users; 42% of pump users wore their device through body scanners, and 44% reported having at least one negative experience with airport security in the past,” he said.

When asked about their greatest fear of flying long-haul, the top four responses were more hyperglycemia and/or hypoglycemia, problems with airport security, losing supplies, and glucose variability. In addition, only about 30% of respondents reported being satisfied with currently available resources intended to help people manage their disease while traveling. “There is a call to action for providers and nonprofits to continue to develop information to better suit the needs of individuals traveling with [type 1 diabetes],” Mr. Schoenberg said. “Furthermore, 55% reported that they use the Internet as their primary source and about one in four use a smart phone regularly for their self-management.”

He concluded that long-haul air travel with type 1 diabetes “is neither straightforward nor easy. Real-life experiences suggest an unmet need for personalized information. There also may be a need to evaluate insulin and devices at altitude and across time zones. Finally, the impacts of long-haul travel become more relevant as we move toward a commercial artificial pancreas system.” The researchers reported having no financial conflicts.

dbrunk@frontlinemedcom.com

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Uwe Platzbecker, MD

COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).

In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.

In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.

The majority of adverse events in both trials were grade 1 and 2.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.

Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.

The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.

In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.

Base study

This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).

In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).

Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).

The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.

In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.

Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.

Extension study

This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.

In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).

In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.

At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).

Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.

Safety

There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.

Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).

Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.

*Data in the abstract differ from data presented at the meeting.

Uwe Platzbecker, MD

COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).

In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.

In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.

The majority of adverse events in both trials were grade 1 and 2.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.

Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.

The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.

In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.

Base study

This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).

In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).

Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).

The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.

In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.

Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.

Extension study

This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.

In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).

In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.

At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).

Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.

Safety

There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.

Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).

Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.

*Data in the abstract differ from data presented at the meeting.

Uwe Platzbecker, MD

COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).

In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.

In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.

The majority of adverse events in both trials were grade 1 and 2.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.

Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.

The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.

In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.

Base study

This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).

In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).

Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).

The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.

In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.

Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.

Extension study

This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.

In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).

In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.

At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).

Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.

Safety

There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.

Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).

Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.

*Data in the abstract differ from data presented at the meeting.

Catriona Jamieson, MD, PhD

Photo courtesy of

UC San Diego Health

New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).

For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.

The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.

Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.

“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”

The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.

ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.

The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.

Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.

After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.

By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.

Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.

“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.

“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”

Catriona Jamieson, MD, PhD

Photo courtesy of

UC San Diego Health

New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).

For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.

The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.

Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.

“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”

The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.

ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.

The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.

Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.

After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.

By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.

Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.

“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.

“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”

Catriona Jamieson, MD, PhD

Photo courtesy of

UC San Diego Health

New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).

For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.

The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.

Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.

“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”

The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.

ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.

The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.

Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.

After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.

By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.

Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.

“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.

“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”