Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended BAY 81-8973, a recombinant factor VIII (FVIII) compound, for approval in the European Union.

BAY 81-8973 is an unmodified, full-length, recombinant FVIII compound intended for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

The CHMP’s recommendation has been relayed to the European Commission, which is expected to make a decision regarding BAY 81-8973 in the coming weeks.

If approved, BAY 81-8973 will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The CHMP’s recommendation is based on results from the LEOPOLD trials, which were presented at the National Hemophilia Foundation’s 67th Annual Meeting last August.

LEOPOLD trials

The LEOPOLD Clinical Development Program consists of 3 multinational clinical trials designed to evaluate the pharmacokinetics, efficacy, and safety of BAY 81-8973 in subjects with severe hemophilia A (<1% FVIII:C).

LEOPOLD I is an open-label, cross-over, phase 3 study of males ages 12 to 65. The objectives were to demonstrate the efficacy and safety of BAY 81-8973 when used as prophylaxis, for the treatment of bleeding episodes, and for maintaining hemostasis during surgery. In LEOPOLD I, investigators assigned subjects to either the 2- or 3-times-weekly dosing regimens based on each patient’s phenotype, prior bleeding history and other factors.

LEOPOLD II is a randomized, cross-over, open-label trial conducted in male subjects ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive BAY 81-8973 either as a low-dose prophylaxis regimen (20-30 IU/kg; n=28) twice per week, high-dose prophylaxis (30-40 IU/kg; n=31) 3 times a week, or on-demand (n=21).

The primary objective was to demonstrate the superiority of prophylaxis over on-demand therapy, with the primary endpoint being bleeding frequency at 12 months.

LEOPOLD Kids is an open-label, non-randomized, phase 3 study. Part A is designed to evaluate the efficacy and safety of BAY 81-8973 for prophylaxis, treatment of bleeds, and surgical management in previously treated children at least 12 years of age with twice or 3 times per week or every other day prophylaxis regimens. Part B of the study, which involves previously untreated patients, is ongoing.

Bayer HealthCare AG has submitted marketing applications for BAY 81-8973 in the US and several other countries and is pursuing regulatory approvals worldwide.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended BAY 81-8973, a recombinant factor VIII (FVIII) compound, for approval in the European Union.

BAY 81-8973 is an unmodified, full-length, recombinant FVIII compound intended for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

The CHMP’s recommendation has been relayed to the European Commission, which is expected to make a decision regarding BAY 81-8973 in the coming weeks.

If approved, BAY 81-8973 will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The CHMP’s recommendation is based on results from the LEOPOLD trials, which were presented at the National Hemophilia Foundation’s 67th Annual Meeting last August.

LEOPOLD trials

The LEOPOLD Clinical Development Program consists of 3 multinational clinical trials designed to evaluate the pharmacokinetics, efficacy, and safety of BAY 81-8973 in subjects with severe hemophilia A (<1% FVIII:C).

LEOPOLD I is an open-label, cross-over, phase 3 study of males ages 12 to 65. The objectives were to demonstrate the efficacy and safety of BAY 81-8973 when used as prophylaxis, for the treatment of bleeding episodes, and for maintaining hemostasis during surgery. In LEOPOLD I, investigators assigned subjects to either the 2- or 3-times-weekly dosing regimens based on each patient’s phenotype, prior bleeding history and other factors.

LEOPOLD II is a randomized, cross-over, open-label trial conducted in male subjects ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive BAY 81-8973 either as a low-dose prophylaxis regimen (20-30 IU/kg; n=28) twice per week, high-dose prophylaxis (30-40 IU/kg; n=31) 3 times a week, or on-demand (n=21).

The primary objective was to demonstrate the superiority of prophylaxis over on-demand therapy, with the primary endpoint being bleeding frequency at 12 months.

LEOPOLD Kids is an open-label, non-randomized, phase 3 study. Part A is designed to evaluate the efficacy and safety of BAY 81-8973 for prophylaxis, treatment of bleeds, and surgical management in previously treated children at least 12 years of age with twice or 3 times per week or every other day prophylaxis regimens. Part B of the study, which involves previously untreated patients, is ongoing.

Bayer HealthCare AG has submitted marketing applications for BAY 81-8973 in the US and several other countries and is pursuing regulatory approvals worldwide.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended BAY 81-8973, a recombinant factor VIII (FVIII) compound, for approval in the European Union.

BAY 81-8973 is an unmodified, full-length, recombinant FVIII compound intended for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

The CHMP’s recommendation has been relayed to the European Commission, which is expected to make a decision regarding BAY 81-8973 in the coming weeks.

If approved, BAY 81-8973 will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The CHMP’s recommendation is based on results from the LEOPOLD trials, which were presented at the National Hemophilia Foundation’s 67th Annual Meeting last August.

LEOPOLD trials

The LEOPOLD Clinical Development Program consists of 3 multinational clinical trials designed to evaluate the pharmacokinetics, efficacy, and safety of BAY 81-8973 in subjects with severe hemophilia A (<1% FVIII:C).

LEOPOLD I is an open-label, cross-over, phase 3 study of males ages 12 to 65. The objectives were to demonstrate the efficacy and safety of BAY 81-8973 when used as prophylaxis, for the treatment of bleeding episodes, and for maintaining hemostasis during surgery. In LEOPOLD I, investigators assigned subjects to either the 2- or 3-times-weekly dosing regimens based on each patient’s phenotype, prior bleeding history and other factors.

LEOPOLD II is a randomized, cross-over, open-label trial conducted in male subjects ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive BAY 81-8973 either as a low-dose prophylaxis regimen (20-30 IU/kg; n=28) twice per week, high-dose prophylaxis (30-40 IU/kg; n=31) 3 times a week, or on-demand (n=21).

The primary objective was to demonstrate the superiority of prophylaxis over on-demand therapy, with the primary endpoint being bleeding frequency at 12 months.

LEOPOLD Kids is an open-label, non-randomized, phase 3 study. Part A is designed to evaluate the efficacy and safety of BAY 81-8973 for prophylaxis, treatment of bleeds, and surgical management in previously treated children at least 12 years of age with twice or 3 times per week or every other day prophylaxis regimens. Part B of the study, which involves previously untreated patients, is ongoing.

Bayer HealthCare AG has submitted marketing applications for BAY 81-8973 in the US and several other countries and is pursuing regulatory approvals worldwide.

Older age, female sex, preoperative chronic steroid use, azotemia, respiratory insufficiency, and coagulopathy all predicted death within a month of colectomy in patients with toxic colitis in the National Surgical Quality Improvement Project database.

The study is the largest to evaluate patients undergoing colectomy for toxic colitis, according to lead investigator Dr. Anand Dayama of the University of California, Davis, and his associates.

Dmitrii Kotin/©Thinkstock

“In a case such as multiorgan failure with toxic colitis, the decision whether ... to operate can be an immensely difficult one,” Dr. Dayama and his colleagues wrote. “This study can help in making informed decisions in order to avoid the medicolegal ramifications of either performing an unnecessary procedure or withholding a lifesaving one,” they wrote in the American Journal of Surgery.

Surgical salvage remains the preferred treatment for patients with medically refractory toxic colitis. To assess outcomes in these patients, the researchers queried the National Surgical Quality Improvement Project database for relevant International Classification of Diseases, Ninth Revision codes between 2005 and 2012 (Am J Surg. 2015 Nov;210[5]:852-8).

The results underscored the severity of toxic colitis, they said. Of 189 patients, more than 26% died within 30 days after surgery, one in five developed postsurgical sepsis, about 17% had cardiovascular complications, 15% had wound complications, and 13% had renal complications. Furthermore, patients who were 70-80 years old had 3.5 times greater odds of dying, compared with younger patients (95% confidence interval, 1.0-12.8), and the increased likelihood of death rose by 22.2 when patients were older than 80 years (95% CI, 5.7-86.4).

Other baseline predictors of 30-day mortality included female sex (odds ratio, 4.1), blood urea nitrogen levels above 40 mg/dL (OR, 4.1), an international normalized ratio exceeding 2 (OR, 7.7), preoperative respiratory insufficiency (OR, 2.73), and a history of chronic steroid use (OR, 3.9), the researchers said. In addition, patients who died within 30 days after surgery were more likely than survivors to have undergone prolonged mechanical ventilation (56% vs. 27%), to have returned to the operating room (18% vs. 14%), to have acute renal failure (28% vs. 6%), or to have suffered a cardiac arrest that required cardiopulmonary resuscitation (18% vs. 7%). Survivors averaged about 2 fewer days in the hospital, compared with patients who died after surgery.

“The high morbidity and mortality of toxic colitis requires early and intensive medical management with IV [intravenous] steroids, antibiotics, decompressive maneuvers, and other resuscitative measures to treat the underlying cause,” they emphasized. “If there is no sign of improvement within 7 days or if there are any signs of deterioration, urgent surgical intervention should be considered.”

The link between female sex and mortality might reflect hormonal changes associated with menopause, but the study did not assess hormonal status or use of hormone therapy, the investigators noted. The association between chronic steroid use and postoperative death “is highly relevant” because long-term steroids are so often used in inflammatory bowel disease, they added. Clinical guidelines (Am J Gastroenterol. 2012 Feb;107:179-94) recommend that patients with acute severe ulcerative colitis proceed to second-line therapy or surgery if they do not respond to 3 days of intravenous steroids, because unnecessary delays can increase the risk of postoperative complications, they added.

The researchers reported no funding sources and had no disclosures.

Older age, female sex, preoperative chronic steroid use, azotemia, respiratory insufficiency, and coagulopathy all predicted death within a month of colectomy in patients with toxic colitis in the National Surgical Quality Improvement Project database.

The study is the largest to evaluate patients undergoing colectomy for toxic colitis, according to lead investigator Dr. Anand Dayama of the University of California, Davis, and his associates.

Dmitrii Kotin/©Thinkstock

“In a case such as multiorgan failure with toxic colitis, the decision whether ... to operate can be an immensely difficult one,” Dr. Dayama and his colleagues wrote. “This study can help in making informed decisions in order to avoid the medicolegal ramifications of either performing an unnecessary procedure or withholding a lifesaving one,” they wrote in the American Journal of Surgery.

Surgical salvage remains the preferred treatment for patients with medically refractory toxic colitis. To assess outcomes in these patients, the researchers queried the National Surgical Quality Improvement Project database for relevant International Classification of Diseases, Ninth Revision codes between 2005 and 2012 (Am J Surg. 2015 Nov;210[5]:852-8).

The results underscored the severity of toxic colitis, they said. Of 189 patients, more than 26% died within 30 days after surgery, one in five developed postsurgical sepsis, about 17% had cardiovascular complications, 15% had wound complications, and 13% had renal complications. Furthermore, patients who were 70-80 years old had 3.5 times greater odds of dying, compared with younger patients (95% confidence interval, 1.0-12.8), and the increased likelihood of death rose by 22.2 when patients were older than 80 years (95% CI, 5.7-86.4).

Other baseline predictors of 30-day mortality included female sex (odds ratio, 4.1), blood urea nitrogen levels above 40 mg/dL (OR, 4.1), an international normalized ratio exceeding 2 (OR, 7.7), preoperative respiratory insufficiency (OR, 2.73), and a history of chronic steroid use (OR, 3.9), the researchers said. In addition, patients who died within 30 days after surgery were more likely than survivors to have undergone prolonged mechanical ventilation (56% vs. 27%), to have returned to the operating room (18% vs. 14%), to have acute renal failure (28% vs. 6%), or to have suffered a cardiac arrest that required cardiopulmonary resuscitation (18% vs. 7%). Survivors averaged about 2 fewer days in the hospital, compared with patients who died after surgery.

“The high morbidity and mortality of toxic colitis requires early and intensive medical management with IV [intravenous] steroids, antibiotics, decompressive maneuvers, and other resuscitative measures to treat the underlying cause,” they emphasized. “If there is no sign of improvement within 7 days or if there are any signs of deterioration, urgent surgical intervention should be considered.”

The link between female sex and mortality might reflect hormonal changes associated with menopause, but the study did not assess hormonal status or use of hormone therapy, the investigators noted. The association between chronic steroid use and postoperative death “is highly relevant” because long-term steroids are so often used in inflammatory bowel disease, they added. Clinical guidelines (Am J Gastroenterol. 2012 Feb;107:179-94) recommend that patients with acute severe ulcerative colitis proceed to second-line therapy or surgery if they do not respond to 3 days of intravenous steroids, because unnecessary delays can increase the risk of postoperative complications, they added.

The researchers reported no funding sources and had no disclosures.

Older age, female sex, preoperative chronic steroid use, azotemia, respiratory insufficiency, and coagulopathy all predicted death within a month of colectomy in patients with toxic colitis in the National Surgical Quality Improvement Project database.

The study is the largest to evaluate patients undergoing colectomy for toxic colitis, according to lead investigator Dr. Anand Dayama of the University of California, Davis, and his associates.

Dmitrii Kotin/©Thinkstock

“In a case such as multiorgan failure with toxic colitis, the decision whether ... to operate can be an immensely difficult one,” Dr. Dayama and his colleagues wrote. “This study can help in making informed decisions in order to avoid the medicolegal ramifications of either performing an unnecessary procedure or withholding a lifesaving one,” they wrote in the American Journal of Surgery.

Surgical salvage remains the preferred treatment for patients with medically refractory toxic colitis. To assess outcomes in these patients, the researchers queried the National Surgical Quality Improvement Project database for relevant International Classification of Diseases, Ninth Revision codes between 2005 and 2012 (Am J Surg. 2015 Nov;210[5]:852-8).

The results underscored the severity of toxic colitis, they said. Of 189 patients, more than 26% died within 30 days after surgery, one in five developed postsurgical sepsis, about 17% had cardiovascular complications, 15% had wound complications, and 13% had renal complications. Furthermore, patients who were 70-80 years old had 3.5 times greater odds of dying, compared with younger patients (95% confidence interval, 1.0-12.8), and the increased likelihood of death rose by 22.2 when patients were older than 80 years (95% CI, 5.7-86.4).

Other baseline predictors of 30-day mortality included female sex (odds ratio, 4.1), blood urea nitrogen levels above 40 mg/dL (OR, 4.1), an international normalized ratio exceeding 2 (OR, 7.7), preoperative respiratory insufficiency (OR, 2.73), and a history of chronic steroid use (OR, 3.9), the researchers said. In addition, patients who died within 30 days after surgery were more likely than survivors to have undergone prolonged mechanical ventilation (56% vs. 27%), to have returned to the operating room (18% vs. 14%), to have acute renal failure (28% vs. 6%), or to have suffered a cardiac arrest that required cardiopulmonary resuscitation (18% vs. 7%). Survivors averaged about 2 fewer days in the hospital, compared with patients who died after surgery.

“The high morbidity and mortality of toxic colitis requires early and intensive medical management with IV [intravenous] steroids, antibiotics, decompressive maneuvers, and other resuscitative measures to treat the underlying cause,” they emphasized. “If there is no sign of improvement within 7 days or if there are any signs of deterioration, urgent surgical intervention should be considered.”

The link between female sex and mortality might reflect hormonal changes associated with menopause, but the study did not assess hormonal status or use of hormone therapy, the investigators noted. The association between chronic steroid use and postoperative death “is highly relevant” because long-term steroids are so often used in inflammatory bowel disease, they added. Clinical guidelines (Am J Gastroenterol. 2012 Feb;107:179-94) recommend that patients with acute severe ulcerative colitis proceed to second-line therapy or surgery if they do not respond to 3 days of intravenous steroids, because unnecessary delays can increase the risk of postoperative complications, they added.

The researchers reported no funding sources and had no disclosures.

CHICAGO – Following a few simple steps can help patients with peripheral artery disease (PAD) get off on the right foot with a home-based exercise program.

“There is growing evidence that PAD patients can walk for exercise at home and improve their walking performance,” Dr. Mary McDermott said at a symposium on vascular surgery sponsored by Northwestern University.

Getting them to do so, however, can be challenging. Patients with peripheral artery disease have greater functional impairment and are at higher risk for cardiovascular disease than is the general population. They also frequently limit their activity to avoid leg problems, as their PAD progresses.

“It’s hard enough to get patients without peripheral artery disease to exercise. As a general internist, I’m well aware of that,” she said. “It’s even more difficult when walking is so painful and uncomfortable.”

At present, the American College of Cardiology/American Heart Association practice guidelines for the management of patients with PAD do not recommend advising patients with PAD to go home and walk.

The guidelines were published in 2005, however, and since 2011, three of four randomized clinical trials of home-based exercise programs have shown a significant gain in walking endurance in patients with PAD, Dr. McDermott of Northwestern University in Chicago, observed.

The most hands-off of these trials showed that patients with symptomatic PAD randomized to a supervised exercise program did the best at treadmill walking, but the home-exercise group who received a step monitor and in-person feedback just once per month did significantly better than did controls assigned light resistance training. Moreover, the home-exercise group had greater change in 6-minute walk distances than either of the other groups (J Am Heart Assoc. 2014 Oct;3[5]:e001107).

“I think the reason for this is that the home-based group was walking outside or perhaps in a mall and getting better at walking over ground,” Dr. McDermott. “The treadmill group was walking only on the treadmill.”

Supervised treadmill exercise may seem like an easier prescription to write, but it faces two major barriers, she said. Most medical insurers, including Medicare, do not pay for supervised exercise for people with PAD and intermittent claudication, and most PAD patients don’t participate. The burden of traveling to an exercise center three times weekly, week after week, to participate can be overwhelming.

“For all of these reasons, we really need to develop home-based exercise programs that work,” Dr. McDermott said.

Based on the successful trials, home-based programs should include monitoring, group support, and goal setting. Dr. McDermott and her colleagues added cognitive-behavioral therapy to group support in the Group Oriented Arterial Leg Study (GOALS), resulting in significant improvement in 6-minute walk distance at 6 months, physical activity over 7 days, and self-perception of walking endurance and speed among home walkers (JAMA. 2013 Jul 3;310[1]:57-65).

Before embarking on any home-exercise program, all patients with PAD should undergo a baseline cardiac stress test to rule out coronary artery ischemia, she cautioned. This also serves to identify any coronary ischemia that may develop during the new walking program.

Once this is performed, Dr. McDermott recommends clinicians:

• Advise patients to walk 5 days per week.

“This may seem like a lot, but it’s important to have them see this as part of their daily routine; just something they get in the habit of doing,” she said.

• Start with 10-15 minutes of walking per exercise session. Tailor the program to the individual patient.

• Walk to maximal leg pain or onset of ischemic pain. Stopping to rest is acceptable.

“A lot of patients, I find, have questions, “ ‘I can’t do this.’ ‘How can this be beneficial?’ So just letting them know that if they just walk and stop, walk and stop, and start with just 10 minutes of that and increase this over time, they really can see improvement,” Dr. McDermott said.

• Increase the walk time by 5 minutes each week.

Increase the duration until the patient is walking at least 30 minutes per session and preferably 45-50 minutes per session, excluding rest periods, she said.

• Advise patients to write down their walking goals.

Specify where they will walk, when they will walk, and the duration of walking to improve compliance, which can slip following hospitalizations or when patients experience acute illness.

• Have patients self-monitor, but also check in with someone for support.

“It doesn’t have to be a nurse,” Dr. McDermott said. “In our studies, we’ve used bachelor’s degree-level people, but told them what to look for. They can do this and the patient feels there is someone they’re accountable to.”

Dr. McDermott and her colleagues are testing the boundaries of support in the ongoing HONOR trial, which includes four weekly visits to an exercise center in phase I to meet the telephone coach, learn to use a Fitbit monitor, and learn the behavioral skills necessary for long-term adherence. Phase II, however, is entirely home based and includes only Fitbit self-monitoring, regular telephone calls from the coach for feedback, use of the study website, and optional group telephone calls.

The bottom line with any program is for patients to understand it must be indefinite to maintain improvement.

“Unfortunately, if they don’t stick with it, they will slide back,” she cautioned.

Dr. McDermott reported research funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute (PCORI), and Novartis.

[email protected]

CHICAGO – Following a few simple steps can help patients with peripheral artery disease (PAD) get off on the right foot with a home-based exercise program.

“There is growing evidence that PAD patients can walk for exercise at home and improve their walking performance,” Dr. Mary McDermott said at a symposium on vascular surgery sponsored by Northwestern University.

Getting them to do so, however, can be challenging. Patients with peripheral artery disease have greater functional impairment and are at higher risk for cardiovascular disease than is the general population. They also frequently limit their activity to avoid leg problems, as their PAD progresses.

“It’s hard enough to get patients without peripheral artery disease to exercise. As a general internist, I’m well aware of that,” she said. “It’s even more difficult when walking is so painful and uncomfortable.”

At present, the American College of Cardiology/American Heart Association practice guidelines for the management of patients with PAD do not recommend advising patients with PAD to go home and walk.

The guidelines were published in 2005, however, and since 2011, three of four randomized clinical trials of home-based exercise programs have shown a significant gain in walking endurance in patients with PAD, Dr. McDermott of Northwestern University in Chicago, observed.

The most hands-off of these trials showed that patients with symptomatic PAD randomized to a supervised exercise program did the best at treadmill walking, but the home-exercise group who received a step monitor and in-person feedback just once per month did significantly better than did controls assigned light resistance training. Moreover, the home-exercise group had greater change in 6-minute walk distances than either of the other groups (J Am Heart Assoc. 2014 Oct;3[5]:e001107).

“I think the reason for this is that the home-based group was walking outside or perhaps in a mall and getting better at walking over ground,” Dr. McDermott. “The treadmill group was walking only on the treadmill.”

Supervised treadmill exercise may seem like an easier prescription to write, but it faces two major barriers, she said. Most medical insurers, including Medicare, do not pay for supervised exercise for people with PAD and intermittent claudication, and most PAD patients don’t participate. The burden of traveling to an exercise center three times weekly, week after week, to participate can be overwhelming.

“For all of these reasons, we really need to develop home-based exercise programs that work,” Dr. McDermott said.

Based on the successful trials, home-based programs should include monitoring, group support, and goal setting. Dr. McDermott and her colleagues added cognitive-behavioral therapy to group support in the Group Oriented Arterial Leg Study (GOALS), resulting in significant improvement in 6-minute walk distance at 6 months, physical activity over 7 days, and self-perception of walking endurance and speed among home walkers (JAMA. 2013 Jul 3;310[1]:57-65).

Before embarking on any home-exercise program, all patients with PAD should undergo a baseline cardiac stress test to rule out coronary artery ischemia, she cautioned. This also serves to identify any coronary ischemia that may develop during the new walking program.

Once this is performed, Dr. McDermott recommends clinicians:

• Advise patients to walk 5 days per week.

“This may seem like a lot, but it’s important to have them see this as part of their daily routine; just something they get in the habit of doing,” she said.

• Start with 10-15 minutes of walking per exercise session. Tailor the program to the individual patient.

• Walk to maximal leg pain or onset of ischemic pain. Stopping to rest is acceptable.

“A lot of patients, I find, have questions, “ ‘I can’t do this.’ ‘How can this be beneficial?’ So just letting them know that if they just walk and stop, walk and stop, and start with just 10 minutes of that and increase this over time, they really can see improvement,” Dr. McDermott said.

• Increase the walk time by 5 minutes each week.

Increase the duration until the patient is walking at least 30 minutes per session and preferably 45-50 minutes per session, excluding rest periods, she said.

• Advise patients to write down their walking goals.

Specify where they will walk, when they will walk, and the duration of walking to improve compliance, which can slip following hospitalizations or when patients experience acute illness.

• Have patients self-monitor, but also check in with someone for support.

“It doesn’t have to be a nurse,” Dr. McDermott said. “In our studies, we’ve used bachelor’s degree-level people, but told them what to look for. They can do this and the patient feels there is someone they’re accountable to.”

Dr. McDermott and her colleagues are testing the boundaries of support in the ongoing HONOR trial, which includes four weekly visits to an exercise center in phase I to meet the telephone coach, learn to use a Fitbit monitor, and learn the behavioral skills necessary for long-term adherence. Phase II, however, is entirely home based and includes only Fitbit self-monitoring, regular telephone calls from the coach for feedback, use of the study website, and optional group telephone calls.

The bottom line with any program is for patients to understand it must be indefinite to maintain improvement.

“Unfortunately, if they don’t stick with it, they will slide back,” she cautioned.

Dr. McDermott reported research funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute (PCORI), and Novartis.

[email protected]

CHICAGO – Following a few simple steps can help patients with peripheral artery disease (PAD) get off on the right foot with a home-based exercise program.

“There is growing evidence that PAD patients can walk for exercise at home and improve their walking performance,” Dr. Mary McDermott said at a symposium on vascular surgery sponsored by Northwestern University.

Getting them to do so, however, can be challenging. Patients with peripheral artery disease have greater functional impairment and are at higher risk for cardiovascular disease than is the general population. They also frequently limit their activity to avoid leg problems, as their PAD progresses.

“It’s hard enough to get patients without peripheral artery disease to exercise. As a general internist, I’m well aware of that,” she said. “It’s even more difficult when walking is so painful and uncomfortable.”

At present, the American College of Cardiology/American Heart Association practice guidelines for the management of patients with PAD do not recommend advising patients with PAD to go home and walk.

The guidelines were published in 2005, however, and since 2011, three of four randomized clinical trials of home-based exercise programs have shown a significant gain in walking endurance in patients with PAD, Dr. McDermott of Northwestern University in Chicago, observed.

The most hands-off of these trials showed that patients with symptomatic PAD randomized to a supervised exercise program did the best at treadmill walking, but the home-exercise group who received a step monitor and in-person feedback just once per month did significantly better than did controls assigned light resistance training. Moreover, the home-exercise group had greater change in 6-minute walk distances than either of the other groups (J Am Heart Assoc. 2014 Oct;3[5]:e001107).

“I think the reason for this is that the home-based group was walking outside or perhaps in a mall and getting better at walking over ground,” Dr. McDermott. “The treadmill group was walking only on the treadmill.”

Supervised treadmill exercise may seem like an easier prescription to write, but it faces two major barriers, she said. Most medical insurers, including Medicare, do not pay for supervised exercise for people with PAD and intermittent claudication, and most PAD patients don’t participate. The burden of traveling to an exercise center three times weekly, week after week, to participate can be overwhelming.

“For all of these reasons, we really need to develop home-based exercise programs that work,” Dr. McDermott said.

Based on the successful trials, home-based programs should include monitoring, group support, and goal setting. Dr. McDermott and her colleagues added cognitive-behavioral therapy to group support in the Group Oriented Arterial Leg Study (GOALS), resulting in significant improvement in 6-minute walk distance at 6 months, physical activity over 7 days, and self-perception of walking endurance and speed among home walkers (JAMA. 2013 Jul 3;310[1]:57-65).

Before embarking on any home-exercise program, all patients with PAD should undergo a baseline cardiac stress test to rule out coronary artery ischemia, she cautioned. This also serves to identify any coronary ischemia that may develop during the new walking program.

Once this is performed, Dr. McDermott recommends clinicians:

• Advise patients to walk 5 days per week.

“This may seem like a lot, but it’s important to have them see this as part of their daily routine; just something they get in the habit of doing,” she said.

• Start with 10-15 minutes of walking per exercise session. Tailor the program to the individual patient.

• Walk to maximal leg pain or onset of ischemic pain. Stopping to rest is acceptable.

“A lot of patients, I find, have questions, “ ‘I can’t do this.’ ‘How can this be beneficial?’ So just letting them know that if they just walk and stop, walk and stop, and start with just 10 minutes of that and increase this over time, they really can see improvement,” Dr. McDermott said.

• Increase the walk time by 5 minutes each week.

Increase the duration until the patient is walking at least 30 minutes per session and preferably 45-50 minutes per session, excluding rest periods, she said.

• Advise patients to write down their walking goals.

Specify where they will walk, when they will walk, and the duration of walking to improve compliance, which can slip following hospitalizations or when patients experience acute illness.

• Have patients self-monitor, but also check in with someone for support.

“It doesn’t have to be a nurse,” Dr. McDermott said. “In our studies, we’ve used bachelor’s degree-level people, but told them what to look for. They can do this and the patient feels there is someone they’re accountable to.”

Dr. McDermott and her colleagues are testing the boundaries of support in the ongoing HONOR trial, which includes four weekly visits to an exercise center in phase I to meet the telephone coach, learn to use a Fitbit monitor, and learn the behavioral skills necessary for long-term adherence. Phase II, however, is entirely home based and includes only Fitbit self-monitoring, regular telephone calls from the coach for feedback, use of the study website, and optional group telephone calls.

The bottom line with any program is for patients to understand it must be indefinite to maintain improvement.

“Unfortunately, if they don’t stick with it, they will slide back,” she cautioned.

Dr. McDermott reported research funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute (PCORI), and Novartis.

[email protected]

Drop of blood

Researchers say they have created a biosensor capable of counting blood cells electrically using only a drop of blood.

The microfluidic device can measure red blood cell, platelet, and white blood cell counts using as little as 11 µL of blood.

The device electrically counts the different types of blood cells based on their size and membrane properties.

To count leukocyte and its differentials, red blood cells are selectively lysed, and the remaining white blood cells are individually counted. Specific cells like neutrophils can be counted using multi-frequency analysis, which probes the membrane properties of the cells.

For red blood cells and platelets, 1 µL of whole blood is diluted with PBS on-chip, and the cells are counted electrically. The total time for measurement is under 20 minutes.

The researchers described this device in TECHNOLOGY.

“Our biosensor exhibits the potential to improve patient care in a spectrum of settings,” said Rashid Bashir, PhD, of the University of Illinois at Urbana-Champaign.

He noted that the device could be particularly useful in resource-limited settings where laboratory tests are often inaccessible due to costs, poor prevalence of laboratory facilities, and the difficulty of follow-up upon receiving results that take days to process.

“There exists a huge potential to translate our biosensor commercially for blood cell count applications,” added Umer Hassan, PhD, of the University of Illinois at Urbana-Champaign.

“The translation of our technology will result in minimal to no experience requirement for device operation. Even patients can perform the test at the comfort of their home and share the results with their primary care physicians via electronic means too.”

“The technology is scalable, and, in future, we plan to apply it to many other potential applications in the areas of animal diagnostics, blood transfusion analysis, ER/ICU applications, and blood cell counting for chemotherapy management,” Dr Bashir said.

The researchers are now working to further develop a portable prototype of the cell counter.

“The cartridges will be disposable and the size of a credit card,” Dr Umer said. “The base unit or the reader will be portable and possibly hand-held. Our technology has the potential to reduce the cost of the test to less than $10, as compared to $100 or more currently charged.”

Drop of blood

Researchers say they have created a biosensor capable of counting blood cells electrically using only a drop of blood.

The microfluidic device can measure red blood cell, platelet, and white blood cell counts using as little as 11 µL of blood.

The device electrically counts the different types of blood cells based on their size and membrane properties.

To count leukocyte and its differentials, red blood cells are selectively lysed, and the remaining white blood cells are individually counted. Specific cells like neutrophils can be counted using multi-frequency analysis, which probes the membrane properties of the cells.

For red blood cells and platelets, 1 µL of whole blood is diluted with PBS on-chip, and the cells are counted electrically. The total time for measurement is under 20 minutes.

The researchers described this device in TECHNOLOGY.

“Our biosensor exhibits the potential to improve patient care in a spectrum of settings,” said Rashid Bashir, PhD, of the University of Illinois at Urbana-Champaign.

He noted that the device could be particularly useful in resource-limited settings where laboratory tests are often inaccessible due to costs, poor prevalence of laboratory facilities, and the difficulty of follow-up upon receiving results that take days to process.

“There exists a huge potential to translate our biosensor commercially for blood cell count applications,” added Umer Hassan, PhD, of the University of Illinois at Urbana-Champaign.

“The translation of our technology will result in minimal to no experience requirement for device operation. Even patients can perform the test at the comfort of their home and share the results with their primary care physicians via electronic means too.”

“The technology is scalable, and, in future, we plan to apply it to many other potential applications in the areas of animal diagnostics, blood transfusion analysis, ER/ICU applications, and blood cell counting for chemotherapy management,” Dr Bashir said.

The researchers are now working to further develop a portable prototype of the cell counter.

“The cartridges will be disposable and the size of a credit card,” Dr Umer said. “The base unit or the reader will be portable and possibly hand-held. Our technology has the potential to reduce the cost of the test to less than $10, as compared to $100 or more currently charged.”

Drop of blood

Researchers say they have created a biosensor capable of counting blood cells electrically using only a drop of blood.

The microfluidic device can measure red blood cell, platelet, and white blood cell counts using as little as 11 µL of blood.

The device electrically counts the different types of blood cells based on their size and membrane properties.

To count leukocyte and its differentials, red blood cells are selectively lysed, and the remaining white blood cells are individually counted. Specific cells like neutrophils can be counted using multi-frequency analysis, which probes the membrane properties of the cells.

For red blood cells and platelets, 1 µL of whole blood is diluted with PBS on-chip, and the cells are counted electrically. The total time for measurement is under 20 minutes.

The researchers described this device in TECHNOLOGY.

“Our biosensor exhibits the potential to improve patient care in a spectrum of settings,” said Rashid Bashir, PhD, of the University of Illinois at Urbana-Champaign.

He noted that the device could be particularly useful in resource-limited settings where laboratory tests are often inaccessible due to costs, poor prevalence of laboratory facilities, and the difficulty of follow-up upon receiving results that take days to process.

“There exists a huge potential to translate our biosensor commercially for blood cell count applications,” added Umer Hassan, PhD, of the University of Illinois at Urbana-Champaign.

“The translation of our technology will result in minimal to no experience requirement for device operation. Even patients can perform the test at the comfort of their home and share the results with their primary care physicians via electronic means too.”

“The technology is scalable, and, in future, we plan to apply it to many other potential applications in the areas of animal diagnostics, blood transfusion analysis, ER/ICU applications, and blood cell counting for chemotherapy management,” Dr Bashir said.

The researchers are now working to further develop a portable prototype of the cell counter.

“The cartridges will be disposable and the size of a credit card,” Dr Umer said. “The base unit or the reader will be portable and possibly hand-held. Our technology has the potential to reduce the cost of the test to less than $10, as compared to $100 or more currently charged.”

A sickled red blood cell

and a normal one

Image by Betty Pace

Preclinical research suggests a drug used to treat multiple myeloma (MM) might also prove effective in the treatment of sickle cell disease (SCD).

Researchers say this study is the first to reveal how the drug, pomalidomide, increases the production of fetal hemoglobin, which is known to interfere with the sickling of red blood cells.

“We knew the drug would make fetal hemoglobin, but we didn’t know to what extent or how,” said Lionel Blanc, PhD, of the Feinstein Institute for Medical Research in Manhasset, New York.

He and his colleagues reported their findings in Blood.

The researchers’ in vitro experiments revealed that pomalidomide reverses γ-globin silencing during adult erythropoiesis, and the drug delays the maturation of early erythroid precursors without impairing terminal differentiation.

The team also found that pomalidomide selectively targets BCL11A and SOX6 to induce γ-globin synthesis, the drug’s mechanism of action during erythropoiesis is independent of IKZF1 degradation, and pomalidomide partially reprograms adult erythroid progenitors to a fetal-like state.

Finally, the researchers discovered that pomalidomide’s mechanism of action is conserved in cells from SCD patients, and treatment with pomalidomide leads to γ-globin production in MM patients.

“We can also say something else—that hydroxyurea, the only FDA-approved drug for sickle cell anemia, was less effective than pomalidomide and appeared to act through a different mechanism of action,” Dr Blanc said.

“The current therapy is good, but not everyone responds equally to hydroxyurea, and what we hope with pomalidomide is to improve this.”

Dr Blanc and his colleagues plan to launch a clinical trial in the near future to test pomalidomide in young adults with SCD.

A sickled red blood cell

and a normal one

Image by Betty Pace

Preclinical research suggests a drug used to treat multiple myeloma (MM) might also prove effective in the treatment of sickle cell disease (SCD).

Researchers say this study is the first to reveal how the drug, pomalidomide, increases the production of fetal hemoglobin, which is known to interfere with the sickling of red blood cells.

“We knew the drug would make fetal hemoglobin, but we didn’t know to what extent or how,” said Lionel Blanc, PhD, of the Feinstein Institute for Medical Research in Manhasset, New York.

He and his colleagues reported their findings in Blood.

The researchers’ in vitro experiments revealed that pomalidomide reverses γ-globin silencing during adult erythropoiesis, and the drug delays the maturation of early erythroid precursors without impairing terminal differentiation.

The team also found that pomalidomide selectively targets BCL11A and SOX6 to induce γ-globin synthesis, the drug’s mechanism of action during erythropoiesis is independent of IKZF1 degradation, and pomalidomide partially reprograms adult erythroid progenitors to a fetal-like state.

Finally, the researchers discovered that pomalidomide’s mechanism of action is conserved in cells from SCD patients, and treatment with pomalidomide leads to γ-globin production in MM patients.

“We can also say something else—that hydroxyurea, the only FDA-approved drug for sickle cell anemia, was less effective than pomalidomide and appeared to act through a different mechanism of action,” Dr Blanc said.

“The current therapy is good, but not everyone responds equally to hydroxyurea, and what we hope with pomalidomide is to improve this.”

Dr Blanc and his colleagues plan to launch a clinical trial in the near future to test pomalidomide in young adults with SCD.

A sickled red blood cell

and a normal one

Image by Betty Pace

Preclinical research suggests a drug used to treat multiple myeloma (MM) might also prove effective in the treatment of sickle cell disease (SCD).

Researchers say this study is the first to reveal how the drug, pomalidomide, increases the production of fetal hemoglobin, which is known to interfere with the sickling of red blood cells.

“We knew the drug would make fetal hemoglobin, but we didn’t know to what extent or how,” said Lionel Blanc, PhD, of the Feinstein Institute for Medical Research in Manhasset, New York.

He and his colleagues reported their findings in Blood.

The researchers’ in vitro experiments revealed that pomalidomide reverses γ-globin silencing during adult erythropoiesis, and the drug delays the maturation of early erythroid precursors without impairing terminal differentiation.

The team also found that pomalidomide selectively targets BCL11A and SOX6 to induce γ-globin synthesis, the drug’s mechanism of action during erythropoiesis is independent of IKZF1 degradation, and pomalidomide partially reprograms adult erythroid progenitors to a fetal-like state.

Finally, the researchers discovered that pomalidomide’s mechanism of action is conserved in cells from SCD patients, and treatment with pomalidomide leads to γ-globin production in MM patients.

“We can also say something else—that hydroxyurea, the only FDA-approved drug for sickle cell anemia, was less effective than pomalidomide and appeared to act through a different mechanism of action,” Dr Blanc said.

“The current therapy is good, but not everyone responds equally to hydroxyurea, and what we hope with pomalidomide is to improve this.”

Dr Blanc and his colleagues plan to launch a clinical trial in the near future to test pomalidomide in young adults with SCD.

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

Influenza activity dropped slightly in South Carolina, but remained high enough to make it the nation’s hot spot during week 9 of the 2015-2016 U.S. flu season, the Centers for Disease Control and Prevention reported Dec. 18.

The activity of influenza-like illness (ILI) in South Carolina went from level 9 down to level 8 for the week ending Dec. 12 (week 9), but that kept it in the “high” range, according to the CDC report.

The rest of the United States saw a slight increase in activity, with 15 states at level 2 or higher, compared with 13 the week before. New Jersey had the next-highest level of activity after South Carolina, rising from level 5 last week to level 6, which moved it into the “moderate” range.

Minnesota had the largest increase in ILI activity from the previous week, going from level 1 to level 4, and other states with increased activity were Alabama, Colorado, Georgia, Illinois, Nevada, Tennessee, and Virginia. States besides South Carolina with decreased activity were Arizona, Hawaii, Louisiana, Mississippi, and Texas, the CDC data show.

The proportion of outpatient visits nationwide for ILI – defined as a temperature of 100° F or greater and cough and/or sore throat – was 1.9%, continuing to stay below the national baseline of 2.1%, the CDC said.

Outside of the fifty states, Guam reported widespread activity, Puerto Rico reported “moderate” (level 7) activity, and the District of Columbia and the U.S. Virgin Islands reported sporadic activity, the CDC noted.

[email protected]

Influenza activity dropped slightly in South Carolina, but remained high enough to make it the nation’s hot spot during week 9 of the 2015-2016 U.S. flu season, the Centers for Disease Control and Prevention reported Dec. 18.

The activity of influenza-like illness (ILI) in South Carolina went from level 9 down to level 8 for the week ending Dec. 12 (week 9), but that kept it in the “high” range, according to the CDC report.

The rest of the United States saw a slight increase in activity, with 15 states at level 2 or higher, compared with 13 the week before. New Jersey had the next-highest level of activity after South Carolina, rising from level 5 last week to level 6, which moved it into the “moderate” range.

Minnesota had the largest increase in ILI activity from the previous week, going from level 1 to level 4, and other states with increased activity were Alabama, Colorado, Georgia, Illinois, Nevada, Tennessee, and Virginia. States besides South Carolina with decreased activity were Arizona, Hawaii, Louisiana, Mississippi, and Texas, the CDC data show.

The proportion of outpatient visits nationwide for ILI – defined as a temperature of 100° F or greater and cough and/or sore throat – was 1.9%, continuing to stay below the national baseline of 2.1%, the CDC said.

Outside of the fifty states, Guam reported widespread activity, Puerto Rico reported “moderate” (level 7) activity, and the District of Columbia and the U.S. Virgin Islands reported sporadic activity, the CDC noted.

[email protected]

Influenza activity dropped slightly in South Carolina, but remained high enough to make it the nation’s hot spot during week 9 of the 2015-2016 U.S. flu season, the Centers for Disease Control and Prevention reported Dec. 18.

The activity of influenza-like illness (ILI) in South Carolina went from level 9 down to level 8 for the week ending Dec. 12 (week 9), but that kept it in the “high” range, according to the CDC report.

The rest of the United States saw a slight increase in activity, with 15 states at level 2 or higher, compared with 13 the week before. New Jersey had the next-highest level of activity after South Carolina, rising from level 5 last week to level 6, which moved it into the “moderate” range.

Minnesota had the largest increase in ILI activity from the previous week, going from level 1 to level 4, and other states with increased activity were Alabama, Colorado, Georgia, Illinois, Nevada, Tennessee, and Virginia. States besides South Carolina with decreased activity were Arizona, Hawaii, Louisiana, Mississippi, and Texas, the CDC data show.

The proportion of outpatient visits nationwide for ILI – defined as a temperature of 100° F or greater and cough and/or sore throat – was 1.9%, continuing to stay below the national baseline of 2.1%, the CDC said.

Outside of the fifty states, Guam reported widespread activity, Puerto Rico reported “moderate” (level 7) activity, and the District of Columbia and the U.S. Virgin Islands reported sporadic activity, the CDC noted.

[email protected]

SAN FRANCISCO – Novel targeted agents offer more options for treating chronic lymphocytic leukemia (CLL), and if properly leveraged, may be able to shorten the time on treatment, improving acceptability to patients and possibly reducing treatment costs, according to Dr. William G. Wierda.

BTK inhibitors

Agents that inhibit Bruton tyrosine kinase (BTK) block signaling through the B-cell receptor in CLL, triggering apoptosis, said Dr. Wierda, professor and medical director, department of leukemia, division of cancer medicine, at the University of Texas MD Anderson Cancer Center in Houston. One such agent, ibrutinib (Imbruvica), is approved by the Food and Drug Administration for treatment of relapsed CLL and for treatment of newly diagnosed CLL having 17p deletion, a high-risk factor.

Results from RESONATE-2, a randomized trial comparing ibrutinib with chlorambucil as frontline therapy in older adults with CLL or small lymphocytic lymphoma, will be reported later this year. “We don’t know the details of that publicly yet, but we do know from a press release that it is a positive trial and showed improvement in outcomes for ibrutinib-treated patients. With that data, we will likely have an expanded label for ibrutinib into the frontline setting, at least for the elderly population,” he said at the NCCN Annual Congress: Hematologic Malignancies.

Longer-term data, collected 3 years after patients started ibrutinib monotherapy, have been very good, with overall response rates of 90% in those with relapsed or refractory disease and 87% in those with treatment-naive disease (ASCO 2014. Abstract 7014). “The last time I saw these data updated, the complete remission portions have increased. So as patients remain on the treatment, responses do improve,” Dr. Wierda noted. Complete remission rates now are about 14% and 24%, respectively. Median progression-free survival has not been reached in either group.

Data from the randomized RESONATE trial, which led to ibrutinib’s approval in relapsed CLL, showed benefit relative to ofatumumab across subgroups, including patients who had disease that was refractory to purine analogs, who had the 17p deletion and who had received at least three prior regimens (ASCO 2014. Abstract LBA7008).

The main grade 3 or 4 toxicity of ibrutinib in patients with CLL is infections, but atrial fibrillation and bleeding/hemorrhage are each seen in about 5% of patients. “The trials all excluded patients on warfarin, so we do not recommend treating patients with ibrutinib who are on warfarin,” Dr. Wierda commented. “If patients are anticoagulated on warfarin and we want to put them on ibrutinib, I will usually switch them over to something like Xarelto [rivaroxaban],” he said. Toxicity generally declines with longer treatment.

Discontinuations because of toxicity or Richter transformation usually occur within the first 18 months (JAMA Oncol. 2015;1[1]:80-7). “The concerning [point] for me though is the patients who develop refractory disease. … The incidence starts to go up significantly as you go out beyond 30 or 36 months,” he said. “We are reviewing our data right now to see if we make a similar observation. But that suggests to me that the longer the patients stay on treatment, the more at risk they are for progressing and developing refractory disease.”

The HELIOS trial tested addition of ibrutinib to bendamustine (Treanda) and rituximab (Rituxan) (ASCO 2015. Abstract LBA7005). Results showed superior progression-free survival with the three-drug combination. “But the question that always comes up when this data is presented is, well, how would it compare with ibrutinib monotherapy? Until that question for me is adequately addressed … I would probably be inclined to give patients ibrutinib monotherapy over the combination,” Dr. Wierda said.

Trials are testing a wide range of other combinations. “To me, this suggests that we really don’t have a direction or a rational strategy for combinations with these agents. … Right now, I’m excited about combining ibrutinib with venetoclax. … They seem clinically complementary, and there is some laboratory data that suggests as well that there will be a complementary mechanism of action.”

PI3 kinase inhibitors

Inhibitors of PI3 kinase also block signaling through the B-cell receptor. In this drug class, idelalisib (Zydelig) is approved for treating relapsed CLL in combination with rituximab.

The phase III trial establishing efficacy of this combination showed that it improved both progression-free and overall survival over rituximab alone (ASH 2014. Abstract 330). Median progression-free survival was 19.4 months. There was similar benefit across various subgroups, including patients with 17p deletion or an unmutated IGHV gene, another high-risk factor.

One of the main toxicities of idelalisib, elevation of liver function test results, typically occurs early and is usually not treatment limiting. Colitis occurs with two predominant patterns: early onset and late onset. “The early colitis in my experience hasn’t necessarily been treatment limiting. We can usually get those patients through their diarrhea [by] withholding the drug; sometimes we’ll give budesonide, and can restart the drug at a lower dose,” Dr. Wierda said. “It’s the late colitis that we have difficulty with – colitis that occurs after patients have been on 3 months, 6 months. And in my experience, those patients have had more severe colitis, and it’s been more treatment limiting.”

Ongoing trials are testing idelalisib in combinations for CLL as well. “Certainly, there’s a number of strategies, and as with ibrutinib, it’s difficult for me to identify a rational combination or a clear combination that I think is going to be superior or a significant advance,” he said. Trials are also testing other PI3 kinase inhibitors, such as duvelisib (IPI-145), now in a phase III registration trial in patients with relapsed or refractory disease.

BCL-2 inhibitors

The investigational agent venetoclax (formerly ABT-199/GDC-199) inhibits BCL-2, which is overexpressed in CLL and renders the cells resistant to apoptosis. It has advanced to a pair of phase III trials, one testing it when combined with rituximab and the other when combined with obinutuzumab (Gazyva).

When used as monotherapy for patients with relapsed disease, venetoclax achieved an overall response rate of 77% and a complete response rate of 23% (EHA 2014. Abstract S702). Benefit was similar among high-risk groups, including patients with the 17p deletion or fludarabine-refractory disease. With a median follow-up of 5.3 months, median progression-free survival for patients treated at the full dose has not been reached.

In earlier trials, venetoclax was associated with a problematic tumor lysis syndrome, according to Dr. Wierda. But that issue has largely been resolved by starting at a low dose and escalating gradually to a full dose; in the trial, it was seen in 7% of patients. The most common grade 3 or 4 adverse event was neutropenia, seen in 33% of patients; however, this toxicity can usually be managed with growth factors and dose reduction, he said.

The combination of venetoclax with rituximab in relapsed CLL yields an 88% overall response rate and a 31% complete response rate (ASH 2014. Abstract 325). Respective values were 78% and 22% in patients with 17p deletion. Moreover, some patients were found to have become negative for minimal residual disease on the combination, although it was not systematically assessed, Dr. Wierda noted.

“Venetoclax is a drug we will hear more about. … It has activity. I think it has a future in treating CLL, and it will be approved in time,” he said.

Leveraging targeted therapies

These new targeted agents, and others in the pipeline, could potentially be leveraged in several ways to improve CLL treatment strategies, according to Dr. Wierda.

Importantly, if ibrutinib becomes approved for universal frontline therapy, a large share of patients are likely to achieve partial remission. “We know if patients are in partial remission, you can’t really stop their treatment on ibrutinib; they will progress. And there was some data reported at ASH [American Society of Hematology] this past year that patients who were on a lower dose or patients who had dose interruption did poorer,” he said. Furthermore, most patients don’t like to be on treatment indefinitely.

“So we’re working on trials to expand our options for consolidation strategies in patients who have been on ibrutinib. We are trying to push them over into a complete remission by adding additional agents,” he explained.

For example, an ongoing trial is testing addition of nivolumab (Opdivo), an immune checkpoint inhibitor, in patients who have been on ibrutinib for at least 9 months and still have a partial remission. “The strategy with that is to try to consolidate them and to get them into a deep remission, where we can have a discussion about holding their treatment or stopping their treatment, or at least to the point where we are comfortable doing that,” he said.

Dr. Wierda disclosed that he has various relationships with AbbVie, Ascerta, Celgene, Emergent BioSolutions, Genentech, Genzyme, Gilead Sciences, GlaxoSmithKline, Juno Therapeutics, Karyopharm, Kite Pharma, Merck, Novartis Pharmaceuticals, Pharmacyclics, Roche Laboratories, and Sanofi-Aventis U.S.

SAN FRANCISCO – Novel targeted agents offer more options for treating chronic lymphocytic leukemia (CLL), and if properly leveraged, may be able to shorten the time on treatment, improving acceptability to patients and possibly reducing treatment costs, according to Dr. William G. Wierda.

BTK inhibitors

Agents that inhibit Bruton tyrosine kinase (BTK) block signaling through the B-cell receptor in CLL, triggering apoptosis, said Dr. Wierda, professor and medical director, department of leukemia, division of cancer medicine, at the University of Texas MD Anderson Cancer Center in Houston. One such agent, ibrutinib (Imbruvica), is approved by the Food and Drug Administration for treatment of relapsed CLL and for treatment of newly diagnosed CLL having 17p deletion, a high-risk factor.

Results from RESONATE-2, a randomized trial comparing ibrutinib with chlorambucil as frontline therapy in older adults with CLL or small lymphocytic lymphoma, will be reported later this year. “We don’t know the details of that publicly yet, but we do know from a press release that it is a positive trial and showed improvement in outcomes for ibrutinib-treated patients. With that data, we will likely have an expanded label for ibrutinib into the frontline setting, at least for the elderly population,” he said at the NCCN Annual Congress: Hematologic Malignancies.

Longer-term data, collected 3 years after patients started ibrutinib monotherapy, have been very good, with overall response rates of 90% in those with relapsed or refractory disease and 87% in those with treatment-naive disease (ASCO 2014. Abstract 7014). “The last time I saw these data updated, the complete remission portions have increased. So as patients remain on the treatment, responses do improve,” Dr. Wierda noted. Complete remission rates now are about 14% and 24%, respectively. Median progression-free survival has not been reached in either group.

Data from the randomized RESONATE trial, which led to ibrutinib’s approval in relapsed CLL, showed benefit relative to ofatumumab across subgroups, including patients who had disease that was refractory to purine analogs, who had the 17p deletion and who had received at least three prior regimens (ASCO 2014. Abstract LBA7008).

The main grade 3 or 4 toxicity of ibrutinib in patients with CLL is infections, but atrial fibrillation and bleeding/hemorrhage are each seen in about 5% of patients. “The trials all excluded patients on warfarin, so we do not recommend treating patients with ibrutinib who are on warfarin,” Dr. Wierda commented. “If patients are anticoagulated on warfarin and we want to put them on ibrutinib, I will usually switch them over to something like Xarelto [rivaroxaban],” he said. Toxicity generally declines with longer treatment.

Discontinuations because of toxicity or Richter transformation usually occur within the first 18 months (JAMA Oncol. 2015;1[1]:80-7). “The concerning [point] for me though is the patients who develop refractory disease. … The incidence starts to go up significantly as you go out beyond 30 or 36 months,” he said. “We are reviewing our data right now to see if we make a similar observation. But that suggests to me that the longer the patients stay on treatment, the more at risk they are for progressing and developing refractory disease.”

The HELIOS trial tested addition of ibrutinib to bendamustine (Treanda) and rituximab (Rituxan) (ASCO 2015. Abstract LBA7005). Results showed superior progression-free survival with the three-drug combination. “But the question that always comes up when this data is presented is, well, how would it compare with ibrutinib monotherapy? Until that question for me is adequately addressed … I would probably be inclined to give patients ibrutinib monotherapy over the combination,” Dr. Wierda said.

Trials are testing a wide range of other combinations. “To me, this suggests that we really don’t have a direction or a rational strategy for combinations with these agents. … Right now, I’m excited about combining ibrutinib with venetoclax. … They seem clinically complementary, and there is some laboratory data that suggests as well that there will be a complementary mechanism of action.”

PI3 kinase inhibitors

Inhibitors of PI3 kinase also block signaling through the B-cell receptor. In this drug class, idelalisib (Zydelig) is approved for treating relapsed CLL in combination with rituximab.

The phase III trial establishing efficacy of this combination showed that it improved both progression-free and overall survival over rituximab alone (ASH 2014. Abstract 330). Median progression-free survival was 19.4 months. There was similar benefit across various subgroups, including patients with 17p deletion or an unmutated IGHV gene, another high-risk factor.

One of the main toxicities of idelalisib, elevation of liver function test results, typically occurs early and is usually not treatment limiting. Colitis occurs with two predominant patterns: early onset and late onset. “The early colitis in my experience hasn’t necessarily been treatment limiting. We can usually get those patients through their diarrhea [by] withholding the drug; sometimes we’ll give budesonide, and can restart the drug at a lower dose,” Dr. Wierda said. “It’s the late colitis that we have difficulty with – colitis that occurs after patients have been on 3 months, 6 months. And in my experience, those patients have had more severe colitis, and it’s been more treatment limiting.”

Ongoing trials are testing idelalisib in combinations for CLL as well. “Certainly, there’s a number of strategies, and as with ibrutinib, it’s difficult for me to identify a rational combination or a clear combination that I think is going to be superior or a significant advance,” he said. Trials are also testing other PI3 kinase inhibitors, such as duvelisib (IPI-145), now in a phase III registration trial in patients with relapsed or refractory disease.

BCL-2 inhibitors

The investigational agent venetoclax (formerly ABT-199/GDC-199) inhibits BCL-2, which is overexpressed in CLL and renders the cells resistant to apoptosis. It has advanced to a pair of phase III trials, one testing it when combined with rituximab and the other when combined with obinutuzumab (Gazyva).

When used as monotherapy for patients with relapsed disease, venetoclax achieved an overall response rate of 77% and a complete response rate of 23% (EHA 2014. Abstract S702). Benefit was similar among high-risk groups, including patients with the 17p deletion or fludarabine-refractory disease. With a median follow-up of 5.3 months, median progression-free survival for patients treated at the full dose has not been reached.

In earlier trials, venetoclax was associated with a problematic tumor lysis syndrome, according to Dr. Wierda. But that issue has largely been resolved by starting at a low dose and escalating gradually to a full dose; in the trial, it was seen in 7% of patients. The most common grade 3 or 4 adverse event was neutropenia, seen in 33% of patients; however, this toxicity can usually be managed with growth factors and dose reduction, he said.

The combination of venetoclax with rituximab in relapsed CLL yields an 88% overall response rate and a 31% complete response rate (ASH 2014. Abstract 325). Respective values were 78% and 22% in patients with 17p deletion. Moreover, some patients were found to have become negative for minimal residual disease on the combination, although it was not systematically assessed, Dr. Wierda noted.

“Venetoclax is a drug we will hear more about. … It has activity. I think it has a future in treating CLL, and it will be approved in time,” he said.

Leveraging targeted therapies

These new targeted agents, and others in the pipeline, could potentially be leveraged in several ways to improve CLL treatment strategies, according to Dr. Wierda.

Importantly, if ibrutinib becomes approved for universal frontline therapy, a large share of patients are likely to achieve partial remission. “We know if patients are in partial remission, you can’t really stop their treatment on ibrutinib; they will progress. And there was some data reported at ASH [American Society of Hematology] this past year that patients who were on a lower dose or patients who had dose interruption did poorer,” he said. Furthermore, most patients don’t like to be on treatment indefinitely.

“So we’re working on trials to expand our options for consolidation strategies in patients who have been on ibrutinib. We are trying to push them over into a complete remission by adding additional agents,” he explained.

For example, an ongoing trial is testing addition of nivolumab (Opdivo), an immune checkpoint inhibitor, in patients who have been on ibrutinib for at least 9 months and still have a partial remission. “The strategy with that is to try to consolidate them and to get them into a deep remission, where we can have a discussion about holding their treatment or stopping their treatment, or at least to the point where we are comfortable doing that,” he said.

Dr. Wierda disclosed that he has various relationships with AbbVie, Ascerta, Celgene, Emergent BioSolutions, Genentech, Genzyme, Gilead Sciences, GlaxoSmithKline, Juno Therapeutics, Karyopharm, Kite Pharma, Merck, Novartis Pharmaceuticals, Pharmacyclics, Roche Laboratories, and Sanofi-Aventis U.S.

SAN FRANCISCO – Novel targeted agents offer more options for treating chronic lymphocytic leukemia (CLL), and if properly leveraged, may be able to shorten the time on treatment, improving acceptability to patients and possibly reducing treatment costs, according to Dr. William G. Wierda.

BTK inhibitors

Agents that inhibit Bruton tyrosine kinase (BTK) block signaling through the B-cell receptor in CLL, triggering apoptosis, said Dr. Wierda, professor and medical director, department of leukemia, division of cancer medicine, at the University of Texas MD Anderson Cancer Center in Houston. One such agent, ibrutinib (Imbruvica), is approved by the Food and Drug Administration for treatment of relapsed CLL and for treatment of newly diagnosed CLL having 17p deletion, a high-risk factor.

Results from RESONATE-2, a randomized trial comparing ibrutinib with chlorambucil as frontline therapy in older adults with CLL or small lymphocytic lymphoma, will be reported later this year. “We don’t know the details of that publicly yet, but we do know from a press release that it is a positive trial and showed improvement in outcomes for ibrutinib-treated patients. With that data, we will likely have an expanded label for ibrutinib into the frontline setting, at least for the elderly population,” he said at the NCCN Annual Congress: Hematologic Malignancies.

Longer-term data, collected 3 years after patients started ibrutinib monotherapy, have been very good, with overall response rates of 90% in those with relapsed or refractory disease and 87% in those with treatment-naive disease (ASCO 2014. Abstract 7014). “The last time I saw these data updated, the complete remission portions have increased. So as patients remain on the treatment, responses do improve,” Dr. Wierda noted. Complete remission rates now are about 14% and 24%, respectively. Median progression-free survival has not been reached in either group.

Data from the randomized RESONATE trial, which led to ibrutinib’s approval in relapsed CLL, showed benefit relative to ofatumumab across subgroups, including patients who had disease that was refractory to purine analogs, who had the 17p deletion and who had received at least three prior regimens (ASCO 2014. Abstract LBA7008).

The main grade 3 or 4 toxicity of ibrutinib in patients with CLL is infections, but atrial fibrillation and bleeding/hemorrhage are each seen in about 5% of patients. “The trials all excluded patients on warfarin, so we do not recommend treating patients with ibrutinib who are on warfarin,” Dr. Wierda commented. “If patients are anticoagulated on warfarin and we want to put them on ibrutinib, I will usually switch them over to something like Xarelto [rivaroxaban],” he said. Toxicity generally declines with longer treatment.

Discontinuations because of toxicity or Richter transformation usually occur within the first 18 months (JAMA Oncol. 2015;1[1]:80-7). “The concerning [point] for me though is the patients who develop refractory disease. … The incidence starts to go up significantly as you go out beyond 30 or 36 months,” he said. “We are reviewing our data right now to see if we make a similar observation. But that suggests to me that the longer the patients stay on treatment, the more at risk they are for progressing and developing refractory disease.”

The HELIOS trial tested addition of ibrutinib to bendamustine (Treanda) and rituximab (Rituxan) (ASCO 2015. Abstract LBA7005). Results showed superior progression-free survival with the three-drug combination. “But the question that always comes up when this data is presented is, well, how would it compare with ibrutinib monotherapy? Until that question for me is adequately addressed … I would probably be inclined to give patients ibrutinib monotherapy over the combination,” Dr. Wierda said.

Trials are testing a wide range of other combinations. “To me, this suggests that we really don’t have a direction or a rational strategy for combinations with these agents. … Right now, I’m excited about combining ibrutinib with venetoclax. … They seem clinically complementary, and there is some laboratory data that suggests as well that there will be a complementary mechanism of action.”

PI3 kinase inhibitors

Inhibitors of PI3 kinase also block signaling through the B-cell receptor. In this drug class, idelalisib (Zydelig) is approved for treating relapsed CLL in combination with rituximab.

The phase III trial establishing efficacy of this combination showed that it improved both progression-free and overall survival over rituximab alone (ASH 2014. Abstract 330). Median progression-free survival was 19.4 months. There was similar benefit across various subgroups, including patients with 17p deletion or an unmutated IGHV gene, another high-risk factor.

One of the main toxicities of idelalisib, elevation of liver function test results, typically occurs early and is usually not treatment limiting. Colitis occurs with two predominant patterns: early onset and late onset. “The early colitis in my experience hasn’t necessarily been treatment limiting. We can usually get those patients through their diarrhea [by] withholding the drug; sometimes we’ll give budesonide, and can restart the drug at a lower dose,” Dr. Wierda said. “It’s the late colitis that we have difficulty with – colitis that occurs after patients have been on 3 months, 6 months. And in my experience, those patients have had more severe colitis, and it’s been more treatment limiting.”

Ongoing trials are testing idelalisib in combinations for CLL as well. “Certainly, there’s a number of strategies, and as with ibrutinib, it’s difficult for me to identify a rational combination or a clear combination that I think is going to be superior or a significant advance,” he said. Trials are also testing other PI3 kinase inhibitors, such as duvelisib (IPI-145), now in a phase III registration trial in patients with relapsed or refractory disease.

BCL-2 inhibitors

The investigational agent venetoclax (formerly ABT-199/GDC-199) inhibits BCL-2, which is overexpressed in CLL and renders the cells resistant to apoptosis. It has advanced to a pair of phase III trials, one testing it when combined with rituximab and the other when combined with obinutuzumab (Gazyva).

When used as monotherapy for patients with relapsed disease, venetoclax achieved an overall response rate of 77% and a complete response rate of 23% (EHA 2014. Abstract S702). Benefit was similar among high-risk groups, including patients with the 17p deletion or fludarabine-refractory disease. With a median follow-up of 5.3 months, median progression-free survival for patients treated at the full dose has not been reached.

In earlier trials, venetoclax was associated with a problematic tumor lysis syndrome, according to Dr. Wierda. But that issue has largely been resolved by starting at a low dose and escalating gradually to a full dose; in the trial, it was seen in 7% of patients. The most common grade 3 or 4 adverse event was neutropenia, seen in 33% of patients; however, this toxicity can usually be managed with growth factors and dose reduction, he said.

The combination of venetoclax with rituximab in relapsed CLL yields an 88% overall response rate and a 31% complete response rate (ASH 2014. Abstract 325). Respective values were 78% and 22% in patients with 17p deletion. Moreover, some patients were found to have become negative for minimal residual disease on the combination, although it was not systematically assessed, Dr. Wierda noted.

“Venetoclax is a drug we will hear more about. … It has activity. I think it has a future in treating CLL, and it will be approved in time,” he said.

Leveraging targeted therapies

These new targeted agents, and others in the pipeline, could potentially be leveraged in several ways to improve CLL treatment strategies, according to Dr. Wierda.

Importantly, if ibrutinib becomes approved for universal frontline therapy, a large share of patients are likely to achieve partial remission. “We know if patients are in partial remission, you can’t really stop their treatment on ibrutinib; they will progress. And there was some data reported at ASH [American Society of Hematology] this past year that patients who were on a lower dose or patients who had dose interruption did poorer,” he said. Furthermore, most patients don’t like to be on treatment indefinitely.

“So we’re working on trials to expand our options for consolidation strategies in patients who have been on ibrutinib. We are trying to push them over into a complete remission by adding additional agents,” he explained.

For example, an ongoing trial is testing addition of nivolumab (Opdivo), an immune checkpoint inhibitor, in patients who have been on ibrutinib for at least 9 months and still have a partial remission. “The strategy with that is to try to consolidate them and to get them into a deep remission, where we can have a discussion about holding their treatment or stopping their treatment, or at least to the point where we are comfortable doing that,” he said.

Dr. Wierda disclosed that he has various relationships with AbbVie, Ascerta, Celgene, Emergent BioSolutions, Genentech, Genzyme, Gilead Sciences, GlaxoSmithKline, Juno Therapeutics, Karyopharm, Kite Pharma, Merck, Novartis Pharmaceuticals, Pharmacyclics, Roche Laboratories, and Sanofi-Aventis U.S.

HIV-infected individuals without any traditional cardiovascular disease risk factors still show signs of vascular thickening, compared with HIV-negative controls, researchers reported in a British study.

A team led by Dr. Kathleen A.M. Rose of the cardiovascular biomedical research unit at London’s Royal Brompton Hospital performed carotid cardiovascular magnetic resonance imaging on 33 HIV-infected patients and 35 HIV-negative controls, with both groups being at low cardiovascular risk. The study showed HIV infection was associated with a significantly greater ratio of carotid wall to outer wall thickness (36.7% vs. 32.5%, P less than .0001) – an indicator of carotid intima-media thickening that has been shown in HIV-negative populations to be predictive of future cardiovascular events.

©pixologicstudio/Thinkstock.com

Women with HIV had an even greater increase in carotid intima-media thickening, compared with men with HIV, according to the study results (JAIDS. 2015 Nov 16. doi: 10.1097/QAI.0000000000000900)

While there were no significant differences between the cases and controls in total carotid lumen volume, carotid artery volume, and carotid wall volume, total wall volume was higher in HIV-infected individuals, and there was a nonsignificant decrease in carotid artery distensibility in the HIV-infected group.

“Although traditional cardiovascular risk factors are highly prevalent and accepted to play a role in HIV-associated cardiovascular disease, the role of long-term cART [combination antiretroviral therapy] and HIV infection itself remains controversial,” wrote Dr. Rose and her coauthors.

The researchers cited earlier studies linking the antiretroviral agents indinavir, abacavir, and lopinavir with increased cardiovascular risk, although they pointed out there was conflicting evidence of a link with type of antiretroviral therapy.

The HIV-infected participants were all stable on combination antiretroviral therapy for a median duration of 7 years (2-21 years), and all had a plasma HIV-1 RNA viral load below 50 copies/mL.

Years of antiretroviral therapy and use of nonnucleoside reverse transcriptase inhibitors or protease inhibitors did not significantly impact carotid intima-media thickness, although patients taking abacavir – which is associated with increased cardiovascular risk – had a lower wall/outer wall ratio than those on zidovudine.

“This result may also reflect a channeling bias whereby clinicians only use abacavir in subjects they consider to have very low cardiovascular risk,” the authors wrote.

Other parameters such as age, ethnicity, CD4 cell count, nadir CD4 cell count, and years since HIV diagnosis did not impact atherosclerosis in HIV-positive subjects.

“Although our study has not followed up patients or controls longitudinally, the diverging lines between the groups with increasing age suggests that HIV infection and/or its treatment may be associated with progression of vascular wall thickening beyond that normally seen with age,” the authors reported.

“As increasing C-IMT [carotid intima-media thickness] has been found to be independently predictive of future stroke and myocardial infarction in HIV-uninfected populations, the findings of this study suggest that the rate of vascular events is likely to remain elevated in HIV-patients despite aggressive treatment of cardiovascular risk factors, highlighting the need for improved patient and health care provider education to detect and manage aggressively early signs of cardiovascular disease.”

The study was supported by the National Institute of Health Research cardiovascular biomedical research unit at Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London. Three authors declared honoraria, grants, sponsorship, and consultancies from the pharmaceutical industry.

HIV-infected individuals without any traditional cardiovascular disease risk factors still show signs of vascular thickening, compared with HIV-negative controls, researchers reported in a British study.

A team led by Dr. Kathleen A.M. Rose of the cardiovascular biomedical research unit at London’s Royal Brompton Hospital performed carotid cardiovascular magnetic resonance imaging on 33 HIV-infected patients and 35 HIV-negative controls, with both groups being at low cardiovascular risk. The study showed HIV infection was associated with a significantly greater ratio of carotid wall to outer wall thickness (36.7% vs. 32.5%, P less than .0001) – an indicator of carotid intima-media thickening that has been shown in HIV-negative populations to be predictive of future cardiovascular events.

©pixologicstudio/Thinkstock.com

Women with HIV had an even greater increase in carotid intima-media thickening, compared with men with HIV, according to the study results (JAIDS. 2015 Nov 16. doi: 10.1097/QAI.0000000000000900)

While there were no significant differences between the cases and controls in total carotid lumen volume, carotid artery volume, and carotid wall volume, total wall volume was higher in HIV-infected individuals, and there was a nonsignificant decrease in carotid artery distensibility in the HIV-infected group.

“Although traditional cardiovascular risk factors are highly prevalent and accepted to play a role in HIV-associated cardiovascular disease, the role of long-term cART [combination antiretroviral therapy] and HIV infection itself remains controversial,” wrote Dr. Rose and her coauthors.

The researchers cited earlier studies linking the antiretroviral agents indinavir, abacavir, and lopinavir with increased cardiovascular risk, although they pointed out there was conflicting evidence of a link with type of antiretroviral therapy.

The HIV-infected participants were all stable on combination antiretroviral therapy for a median duration of 7 years (2-21 years), and all had a plasma HIV-1 RNA viral load below 50 copies/mL.

Years of antiretroviral therapy and use of nonnucleoside reverse transcriptase inhibitors or protease inhibitors did not significantly impact carotid intima-media thickness, although patients taking abacavir – which is associated with increased cardiovascular risk – had a lower wall/outer wall ratio than those on zidovudine.

“This result may also reflect a channeling bias whereby clinicians only use abacavir in subjects they consider to have very low cardiovascular risk,” the authors wrote.

Other parameters such as age, ethnicity, CD4 cell count, nadir CD4 cell count, and years since HIV diagnosis did not impact atherosclerosis in HIV-positive subjects.

“Although our study has not followed up patients or controls longitudinally, the diverging lines between the groups with increasing age suggests that HIV infection and/or its treatment may be associated with progression of vascular wall thickening beyond that normally seen with age,” the authors reported.

“As increasing C-IMT [carotid intima-media thickness] has been found to be independently predictive of future stroke and myocardial infarction in HIV-uninfected populations, the findings of this study suggest that the rate of vascular events is likely to remain elevated in HIV-patients despite aggressive treatment of cardiovascular risk factors, highlighting the need for improved patient and health care provider education to detect and manage aggressively early signs of cardiovascular disease.”

The study was supported by the National Institute of Health Research cardiovascular biomedical research unit at Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London. Three authors declared honoraria, grants, sponsorship, and consultancies from the pharmaceutical industry.

HIV-infected individuals without any traditional cardiovascular disease risk factors still show signs of vascular thickening, compared with HIV-negative controls, researchers reported in a British study.

A team led by Dr. Kathleen A.M. Rose of the cardiovascular biomedical research unit at London’s Royal Brompton Hospital performed carotid cardiovascular magnetic resonance imaging on 33 HIV-infected patients and 35 HIV-negative controls, with both groups being at low cardiovascular risk. The study showed HIV infection was associated with a significantly greater ratio of carotid wall to outer wall thickness (36.7% vs. 32.5%, P less than .0001) – an indicator of carotid intima-media thickening that has been shown in HIV-negative populations to be predictive of future cardiovascular events.

©pixologicstudio/Thinkstock.com

Women with HIV had an even greater increase in carotid intima-media thickening, compared with men with HIV, according to the study results (JAIDS. 2015 Nov 16. doi: 10.1097/QAI.0000000000000900)

While there were no significant differences between the cases and controls in total carotid lumen volume, carotid artery volume, and carotid wall volume, total wall volume was higher in HIV-infected individuals, and there was a nonsignificant decrease in carotid artery distensibility in the HIV-infected group.

“Although traditional cardiovascular risk factors are highly prevalent and accepted to play a role in HIV-associated cardiovascular disease, the role of long-term cART [combination antiretroviral therapy] and HIV infection itself remains controversial,” wrote Dr. Rose and her coauthors.

The researchers cited earlier studies linking the antiretroviral agents indinavir, abacavir, and lopinavir with increased cardiovascular risk, although they pointed out there was conflicting evidence of a link with type of antiretroviral therapy.

The HIV-infected participants were all stable on combination antiretroviral therapy for a median duration of 7 years (2-21 years), and all had a plasma HIV-1 RNA viral load below 50 copies/mL.

Years of antiretroviral therapy and use of nonnucleoside reverse transcriptase inhibitors or protease inhibitors did not significantly impact carotid intima-media thickness, although patients taking abacavir – which is associated with increased cardiovascular risk – had a lower wall/outer wall ratio than those on zidovudine.

“This result may also reflect a channeling bias whereby clinicians only use abacavir in subjects they consider to have very low cardiovascular risk,” the authors wrote.

Other parameters such as age, ethnicity, CD4 cell count, nadir CD4 cell count, and years since HIV diagnosis did not impact atherosclerosis in HIV-positive subjects.

“Although our study has not followed up patients or controls longitudinally, the diverging lines between the groups with increasing age suggests that HIV infection and/or its treatment may be associated with progression of vascular wall thickening beyond that normally seen with age,” the authors reported.

“As increasing C-IMT [carotid intima-media thickness] has been found to be independently predictive of future stroke and myocardial infarction in HIV-uninfected populations, the findings of this study suggest that the rate of vascular events is likely to remain elevated in HIV-patients despite aggressive treatment of cardiovascular risk factors, highlighting the need for improved patient and health care provider education to detect and manage aggressively early signs of cardiovascular disease.”

The study was supported by the National Institute of Health Research cardiovascular biomedical research unit at Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London. Three authors declared honoraria, grants, sponsorship, and consultancies from the pharmaceutical industry.

For many, the making and breaking of New Year’s resolutions has become a humorless cliché. Still, the beginning of a new year is as good a time as any for reflection and inspiration; and if you restrict your fix-it list to a few realistic promises that can actually be kept, resolution time does not have to be such an exercise in futility.

I can’t presume to know what needs improving in your practice, much less your life; but I do know the office issues I get the most questions about. Perhaps the following examples will provide inspiration for assembling a realistic list of your own:

1. Review your October, November, and December claim payments. That is, all payments since ICD-10 launched. Overall, the transition has been surprisingly smooth; the Centers for Medicare & Medicaid Services says the claim denial rate has not increased significantly, and very few rejections are due to incorrect diagnosis coding. But each private payer has its own procedure, so make sure that none of your payers has dropped the ball. The most common problem so far seems to be inconsistent handling of “Z” codes, such as skin cancer screening (Z12.83), so pay particular attention to those.

2. Do a HIPAA risk assessment. The new HIPAA rules have been in effect for more than a year. Is your office up to speed? Review every procedure that involves confidential information; make sure there are no violations. Penalties for carelessness are a lot stiffer now.

3. Encrypt your mobile devices. This is really a subset of No. 2. The biggest HIPAA vulnerability in many practices is laptops and tablets carrying confidential patient information; losing one could be a disaster. Encryption software is cheap and readily available, and a lost or stolen mobile device will probably not be treated as a HIPAA breach if it is properly encrypted.

4. Reduce your accounts receivable by keeping a credit card number on file for each patient, and charging patient-owed balances as they come in. A series of my past columns in the archive at www.edermatologynews.com explains exactly how to do this. Every hotel in the world does it; you should too.

5. Clear your “horizontal file cabinet.” That’s the mess on your desk, all the paperwork you never seem to get to (probably because you’re tweeting or answering e-mail). Set aside an hour or two and get it all done. You’ll find some interesting stuff in there. Then, for every piece of paper that arrives on your desk from now on, follow the DDD Rule: Do it, Delegate it, or Destroy it. Don’t start a new mess.

6. Keep a closer eye on your office finances. Most physicians delegate the bookkeeping, and that’s fine. But ignoring the financial side creates an atmosphere that facilitates embezzlement. Set aside a couple of hours each month to review the books personally. And make sure your employees know you’re doing it.

7. Make sure your long range financial planning is on track. This is another task physicians tend to “set and forget,” but the Great Recession was an eye opener for many of us. Once a year, sit down with your accountant and planner and make sure your investments are well diversified and all other aspects of your finances – budgets, credit ratings, insurance coverage, tax situations, college savings, estate plans, retirement accounts – are in the best shape possible. January is a good time.

8. Back up your data. Now is also an excellent time to verify that the information on your office and personal computers is being backed up – locally and online – on a regular schedule. Don’t wait until something crashes.

9. Take more vacations. Remember Eastern’s First Law: Your last words will NOT be, “I wish I had spent more time in the office.” This is the year to start spending more time enjoying your life, your friends and family, and the world. As John Lennon said, “Life is what happens to you while you’re busy making other plans.”

10. Look at yourself. A private practice lives or dies on the personalities of its physicians, and your staff copies your personality and style. Take a hard, honest look at yourself. Identify your negative personality traits and work to eliminate them. If you have any difficulty finding habits that need changing … ask your spouse. He or she will be happy to explain them in excruciating detail.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

For many, the making and breaking of New Year’s resolutions has become a humorless cliché. Still, the beginning of a new year is as good a time as any for reflection and inspiration; and if you restrict your fix-it list to a few realistic promises that can actually be kept, resolution time does not have to be such an exercise in futility.

I can’t presume to know what needs improving in your practice, much less your life; but I do know the office issues I get the most questions about. Perhaps the following examples will provide inspiration for assembling a realistic list of your own:

1. Review your October, November, and December claim payments. That is, all payments since ICD-10 launched. Overall, the transition has been surprisingly smooth; the Centers for Medicare & Medicaid Services says the claim denial rate has not increased significantly, and very few rejections are due to incorrect diagnosis coding. But each private payer has its own procedure, so make sure that none of your payers has dropped the ball. The most common problem so far seems to be inconsistent handling of “Z” codes, such as skin cancer screening (Z12.83), so pay particular attention to those.

2. Do a HIPAA risk assessment. The new HIPAA rules have been in effect for more than a year. Is your office up to speed? Review every procedure that involves confidential information; make sure there are no violations. Penalties for carelessness are a lot stiffer now.

3. Encrypt your mobile devices. This is really a subset of No. 2. The biggest HIPAA vulnerability in many practices is laptops and tablets carrying confidential patient information; losing one could be a disaster. Encryption software is cheap and readily available, and a lost or stolen mobile device will probably not be treated as a HIPAA breach if it is properly encrypted.

4. Reduce your accounts receivable by keeping a credit card number on file for each patient, and charging patient-owed balances as they come in. A series of my past columns in the archive at www.edermatologynews.com explains exactly how to do this. Every hotel in the world does it; you should too.

5. Clear your “horizontal file cabinet.” That’s the mess on your desk, all the paperwork you never seem to get to (probably because you’re tweeting or answering e-mail). Set aside an hour or two and get it all done. You’ll find some interesting stuff in there. Then, for every piece of paper that arrives on your desk from now on, follow the DDD Rule: Do it, Delegate it, or Destroy it. Don’t start a new mess.

6. Keep a closer eye on your office finances. Most physicians delegate the bookkeeping, and that’s fine. But ignoring the financial side creates an atmosphere that facilitates embezzlement. Set aside a couple of hours each month to review the books personally. And make sure your employees know you’re doing it.

7. Make sure your long range financial planning is on track. This is another task physicians tend to “set and forget,” but the Great Recession was an eye opener for many of us. Once a year, sit down with your accountant and planner and make sure your investments are well diversified and all other aspects of your finances – budgets, credit ratings, insurance coverage, tax situations, college savings, estate plans, retirement accounts – are in the best shape possible. January is a good time.

8. Back up your data. Now is also an excellent time to verify that the information on your office and personal computers is being backed up – locally and online – on a regular schedule. Don’t wait until something crashes.

9. Take more vacations. Remember Eastern’s First Law: Your last words will NOT be, “I wish I had spent more time in the office.” This is the year to start spending more time enjoying your life, your friends and family, and the world. As John Lennon said, “Life is what happens to you while you’re busy making other plans.”

10. Look at yourself. A private practice lives or dies on the personalities of its physicians, and your staff copies your personality and style. Take a hard, honest look at yourself. Identify your negative personality traits and work to eliminate them. If you have any difficulty finding habits that need changing … ask your spouse. He or she will be happy to explain them in excruciating detail.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

For many, the making and breaking of New Year’s resolutions has become a humorless cliché. Still, the beginning of a new year is as good a time as any for reflection and inspiration; and if you restrict your fix-it list to a few realistic promises that can actually be kept, resolution time does not have to be such an exercise in futility.

I can’t presume to know what needs improving in your practice, much less your life; but I do know the office issues I get the most questions about. Perhaps the following examples will provide inspiration for assembling a realistic list of your own:

1. Review your October, November, and December claim payments. That is, all payments since ICD-10 launched. Overall, the transition has been surprisingly smooth; the Centers for Medicare & Medicaid Services says the claim denial rate has not increased significantly, and very few rejections are due to incorrect diagnosis coding. But each private payer has its own procedure, so make sure that none of your payers has dropped the ball. The most common problem so far seems to be inconsistent handling of “Z” codes, such as skin cancer screening (Z12.83), so pay particular attention to those.

2. Do a HIPAA risk assessment. The new HIPAA rules have been in effect for more than a year. Is your office up to speed? Review every procedure that involves confidential information; make sure there are no violations. Penalties for carelessness are a lot stiffer now.

3. Encrypt your mobile devices. This is really a subset of No. 2. The biggest HIPAA vulnerability in many practices is laptops and tablets carrying confidential patient information; losing one could be a disaster. Encryption software is cheap and readily available, and a lost or stolen mobile device will probably not be treated as a HIPAA breach if it is properly encrypted.

4. Reduce your accounts receivable by keeping a credit card number on file for each patient, and charging patient-owed balances as they come in. A series of my past columns in the archive at www.edermatologynews.com explains exactly how to do this. Every hotel in the world does it; you should too.

5. Clear your “horizontal file cabinet.” That’s the mess on your desk, all the paperwork you never seem to get to (probably because you’re tweeting or answering e-mail). Set aside an hour or two and get it all done. You’ll find some interesting stuff in there. Then, for every piece of paper that arrives on your desk from now on, follow the DDD Rule: Do it, Delegate it, or Destroy it. Don’t start a new mess.

6. Keep a closer eye on your office finances. Most physicians delegate the bookkeeping, and that’s fine. But ignoring the financial side creates an atmosphere that facilitates embezzlement. Set aside a couple of hours each month to review the books personally. And make sure your employees know you’re doing it.

7. Make sure your long range financial planning is on track. This is another task physicians tend to “set and forget,” but the Great Recession was an eye opener for many of us. Once a year, sit down with your accountant and planner and make sure your investments are well diversified and all other aspects of your finances – budgets, credit ratings, insurance coverage, tax situations, college savings, estate plans, retirement accounts – are in the best shape possible. January is a good time.

8. Back up your data. Now is also an excellent time to verify that the information on your office and personal computers is being backed up – locally and online – on a regular schedule. Don’t wait until something crashes.

9. Take more vacations. Remember Eastern’s First Law: Your last words will NOT be, “I wish I had spent more time in the office.” This is the year to start spending more time enjoying your life, your friends and family, and the world. As John Lennon said, “Life is what happens to you while you’re busy making other plans.”

10. Look at yourself. A private practice lives or dies on the personalities of its physicians, and your staff copies your personality and style. Take a hard, honest look at yourself. Identify your negative personality traits and work to eliminate them. If you have any difficulty finding habits that need changing … ask your spouse. He or she will be happy to explain them in excruciating detail.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].