A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

Since 2011, HIV incidence appears unchanged in the European Union/European Economic Area with between 29,000 and 33,000 new cases reported annually up to 2015, according to the European Centre for Disease Prevention and Control.

A study in the journal AIDS found that smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy.

copyright alexskopje/Thinkstock

Around a quarter of all people living with HIV in South Africa have achieved viral suppression, a study found, although expanding HIV testing, strengthening prompt linkage to care and further expansion of antiretroviral therapy are needed for the country to reach the 90-90-90 target.

Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial viral suppression, according to a South African study.

A study in New York City found that peer-referral approaches were more efficacious than venue-based sampling for uncovering heterosexuals at high-risk with undiagnosed HIV, and have a vital role to play in efforts to eliminate HIV transmission.

According to a study in AIDS Care, counseling messages for sterilized HIV-positive women should be sensitive to the fact that women may have regret regarding their sterilization decision that may historically have been part of provider recommendations to prevent vertical transmission of HIV.

A recent study found that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection, and the inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages.

A Swiss study found that 22% of HIV post-exposure prophylaxis decisions were risk-discordant due to an exposed person’s request, incorrect estimation of the sexual transmission risk by the physician, or an exposed person’s refusal to accept PEP.

In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing, according to a study in the International Journal of Epidemiology.

Mortality among those untested for HIV contributes a declining portion of deaths among HIV-infected individuals in Rwanda, a recent study found, but the portion of deaths among those lost to follow-up is expected to increase the most over the next decade.

A high proportion of HIV-HCV-coinfected patients had chronic hepatitis C virus infection, according to a study of patients in Southeast Asia. HCV genotype 1 was predominant, and 62% of patients had liver disease warranting prompt treatment.

Early initiation of combination antiretroviral therapy for HIV-infected patients with and without hepatitis coinfections may mitigate or slow down some of liver fibrosis, a Chinese study found, but special attention should be given to those who are older, male, coinfected with HCV.

A recent study showed that Kaposi’s sarcoma-associated herpes virus infects human central nervous system resident cells, primarily neurons, in HIV positive Zambian individuals.

In a pilot study, the use of rosuvastatin for 24 weeks appeared to slow worsening of airflow obstruction and to improve diffusing capacity for carbon monoxide in HIV-infected individuals with abnormal lung function.

A study of HIV-positive adults found that switching to tenofovir disoproxil fumarate (TDF)-based treatment regimens is associated with reductions of bone mineral density and lipid levels and possibly lowered kidney function.

A study in the journal AIDS demonstrated virological 24-weeks efficacy in twice and once daily administered fozivudine-based antiretroviral treatment regimens, although researchers said reduced myelotoxicity of fozivudine needs to be confirmed in a larger trial.

A study in HIV Clinical Trials suggested potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV.

A study in Hepatology found that HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjustment for demographic, lifestyle, metabolic factors, and hepatic fibrosis, suggesting that non-genotype 3 HCV infection may be protective against hepatic steatosis.

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

Since 2011, HIV incidence appears unchanged in the European Union/European Economic Area with between 29,000 and 33,000 new cases reported annually up to 2015, according to the European Centre for Disease Prevention and Control.

A study in the journal AIDS found that smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy.

copyright alexskopje/Thinkstock

Around a quarter of all people living with HIV in South Africa have achieved viral suppression, a study found, although expanding HIV testing, strengthening prompt linkage to care and further expansion of antiretroviral therapy are needed for the country to reach the 90-90-90 target.

Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial viral suppression, according to a South African study.

A study in New York City found that peer-referral approaches were more efficacious than venue-based sampling for uncovering heterosexuals at high-risk with undiagnosed HIV, and have a vital role to play in efforts to eliminate HIV transmission.

According to a study in AIDS Care, counseling messages for sterilized HIV-positive women should be sensitive to the fact that women may have regret regarding their sterilization decision that may historically have been part of provider recommendations to prevent vertical transmission of HIV.

A recent study found that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection, and the inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages.

A Swiss study found that 22% of HIV post-exposure prophylaxis decisions were risk-discordant due to an exposed person’s request, incorrect estimation of the sexual transmission risk by the physician, or an exposed person’s refusal to accept PEP.

In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing, according to a study in the International Journal of Epidemiology.

Mortality among those untested for HIV contributes a declining portion of deaths among HIV-infected individuals in Rwanda, a recent study found, but the portion of deaths among those lost to follow-up is expected to increase the most over the next decade.

A high proportion of HIV-HCV-coinfected patients had chronic hepatitis C virus infection, according to a study of patients in Southeast Asia. HCV genotype 1 was predominant, and 62% of patients had liver disease warranting prompt treatment.

Early initiation of combination antiretroviral therapy for HIV-infected patients with and without hepatitis coinfections may mitigate or slow down some of liver fibrosis, a Chinese study found, but special attention should be given to those who are older, male, coinfected with HCV.

A recent study showed that Kaposi’s sarcoma-associated herpes virus infects human central nervous system resident cells, primarily neurons, in HIV positive Zambian individuals.

In a pilot study, the use of rosuvastatin for 24 weeks appeared to slow worsening of airflow obstruction and to improve diffusing capacity for carbon monoxide in HIV-infected individuals with abnormal lung function.

A study of HIV-positive adults found that switching to tenofovir disoproxil fumarate (TDF)-based treatment regimens is associated with reductions of bone mineral density and lipid levels and possibly lowered kidney function.

A study in the journal AIDS demonstrated virological 24-weeks efficacy in twice and once daily administered fozivudine-based antiretroviral treatment regimens, although researchers said reduced myelotoxicity of fozivudine needs to be confirmed in a larger trial.

A study in HIV Clinical Trials suggested potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV.

A study in Hepatology found that HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjustment for demographic, lifestyle, metabolic factors, and hepatic fibrosis, suggesting that non-genotype 3 HCV infection may be protective against hepatic steatosis.

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

Since 2011, HIV incidence appears unchanged in the European Union/European Economic Area with between 29,000 and 33,000 new cases reported annually up to 2015, according to the European Centre for Disease Prevention and Control.

A study in the journal AIDS found that smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy.

copyright alexskopje/Thinkstock

Around a quarter of all people living with HIV in South Africa have achieved viral suppression, a study found, although expanding HIV testing, strengthening prompt linkage to care and further expansion of antiretroviral therapy are needed for the country to reach the 90-90-90 target.

Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial viral suppression, according to a South African study.

A study in New York City found that peer-referral approaches were more efficacious than venue-based sampling for uncovering heterosexuals at high-risk with undiagnosed HIV, and have a vital role to play in efforts to eliminate HIV transmission.

According to a study in AIDS Care, counseling messages for sterilized HIV-positive women should be sensitive to the fact that women may have regret regarding their sterilization decision that may historically have been part of provider recommendations to prevent vertical transmission of HIV.

A recent study found that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection, and the inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages.

A Swiss study found that 22% of HIV post-exposure prophylaxis decisions were risk-discordant due to an exposed person’s request, incorrect estimation of the sexual transmission risk by the physician, or an exposed person’s refusal to accept PEP.

In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing, according to a study in the International Journal of Epidemiology.

Mortality among those untested for HIV contributes a declining portion of deaths among HIV-infected individuals in Rwanda, a recent study found, but the portion of deaths among those lost to follow-up is expected to increase the most over the next decade.

A high proportion of HIV-HCV-coinfected patients had chronic hepatitis C virus infection, according to a study of patients in Southeast Asia. HCV genotype 1 was predominant, and 62% of patients had liver disease warranting prompt treatment.

Early initiation of combination antiretroviral therapy for HIV-infected patients with and without hepatitis coinfections may mitigate or slow down some of liver fibrosis, a Chinese study found, but special attention should be given to those who are older, male, coinfected with HCV.

A recent study showed that Kaposi’s sarcoma-associated herpes virus infects human central nervous system resident cells, primarily neurons, in HIV positive Zambian individuals.

In a pilot study, the use of rosuvastatin for 24 weeks appeared to slow worsening of airflow obstruction and to improve diffusing capacity for carbon monoxide in HIV-infected individuals with abnormal lung function.

A study of HIV-positive adults found that switching to tenofovir disoproxil fumarate (TDF)-based treatment regimens is associated with reductions of bone mineral density and lipid levels and possibly lowered kidney function.

A study in the journal AIDS demonstrated virological 24-weeks efficacy in twice and once daily administered fozivudine-based antiretroviral treatment regimens, although researchers said reduced myelotoxicity of fozivudine needs to be confirmed in a larger trial.

A study in HIV Clinical Trials suggested potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV.

A study in Hepatology found that HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjustment for demographic, lifestyle, metabolic factors, and hepatic fibrosis, suggesting that non-genotype 3 HCV infection may be protective against hepatic steatosis.

[email protected]

On Twitter @richpizzi

NEW ORLEANS – A significant reduction in 30-day all-cause hospital readmissions after sleeve gastrectomy was accomplished through the first-ever joint national quality improvement collaboration between the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery, John M. Morton, MD, reported at Obesity Week 2016.

The quality improvement program, known as DROP, for Decreasing Readmissions through Opportunities Provided, was developed by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). It was put to the test in a year-long study conducted in 128 nationally representative U.S. hospitals. The study involved a comparison of the participating hospitals’ 30-day all-cause readmission rates following bariatric surgery in the year prior to vs. the year after launch of the DROP project.

Bruce Jancin/Frontline Medical News

Overall, the 30-day all-cause readmission rate after primary laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, or laparoscopic Roux-en-Y gastric bypass dropped only modestly, from 4.76% to 4.61%, a relative reduction of 3.2%. But that’s not the whole story. Hidden within that modest overall result were major improvements, Dr. Morton said at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Of particular interest was the finding that the readmission rate following laparoscopic sleeve gastrectomy decreased from 4.02% to 3.54%, a 12% reduction. That’s an important finding, because sleeve gastrectomy is now by far the most frequently performed type of bariatric surgery in the United States. Indeed, it accounted for 54% of the estimated 196,000 bariatric surgery procedures performed in the country in 2015. Roux-en-Y gastric bypass was a distant second at 23%, followed by surgical revisions at 13.6%.

Moreover, the impact of the DROP initiative appeared to accelerate over time. The initiative as tested consisted of a comprehensive bundle of numerous components addressing preoperative, in-hospital, and postoperative care, and it took a while for hospitals to implement. The 30-day readmission rate following laparoscopic sleeve gastrectomy actually increased by 9.2% in the first 3 months following launch of the DROP initiative. But the readmission rate then took a U-turn, declining by 13.2% in the second quarter compared to the year-before rate, by 16.9% in the third quarter, and falling by 27.1% in the final 3 months of the study.

Mean length of stay for patients undergoing laparoscopic sleeve gastrectomy fell significantly, from 1.9 days pre-DROP to 1.79 days. The DROP intervention also achieved a significant decrease in length of stay for laparoscopic adjustable gastric banding, from 0.5 to 0.42 days.

The rate of readmission within 24 hours post discharge in laparoscopic sleeve gastrectomy patients decreased significantly by 19% after introduction of the DROP program. The trend was favorable, albeit not statistically significant, for the other two bariatric procedures studied.

Of note, hospitals in the two quartiles with the lowest preintervention 30-day all-cause readmission rates post bariatric surgery, with rates of 1.34% and 3.15%, respectively, didn’t derive any further reduction by participating in the DROP program. They already were performing many of the elements included in the intervention. But hospitals in the third quartile significantly improved their 30-day readmission rate from 4.84% to 4.13%, and those in the fourth quartile improved from 7.31% preintervention to 4.47% under the DROP program.

The program had no impact on postoperative leak rates or other surgical complications. However, patient satisfaction scores improved after introduction of the DROP intervention.

The preoperative components of the DROP readmission prevention bundle included a standardized 5-minute educational video featuring a surgeon, nutritionist, pharmacist, and psychologist or psychiatrist, with advice on key issues related to the upcoming operation. That’s also when the visits with the surgeon and a nutritionist were to be scheduled for within 30 days post surgery, and when the patient received phone numbers for the clinic and on-call surgeon in case questions arose later.

The in-hospital elements of the DROP intervention included provision of a clinical roadmap to guide patient expectations, as well as a nutritional consultation. The postoperative components included a day-after-discharge phone call from a nurse or physician assistant, a letter sent to the referring physician containing a discharge summary and recommendations, and a system to make sure that the scheduled follow-up appointments with the surgeon and nutritionist actually take place.

Since adherence to the various components of the DROP bundle varied from hospital to hospital, it was possible for Dr. Morton and his coinvestigators to determine which elements made the most difference in improving 30-day readmission rates. They found that the key difference makers were the nurse’s phone call on the day following discharge and the postoperative visits with the surgeon and nutritionist within the first several weeks.

Asked whether the study findings mean that hospitals that already have a 30-day all-cause readmission rate in the lower half of the national average don’t need to adopt the DROP program, Dr. Morton replied: “One size does not fit all. Maybe some centers don’t need to do all this.”

Thirty-day all-cause readmissions were selected for the first quality improvement project by the MBSAQIP in part because the Centers for Medicare & Medicaid Services has identified it as a priority area for surgery in general. Also, Dr. Morton was a coinvestigator in a study that found many readmissions after bariatric surgery are tied to preventable causes, including dietary indiscretions resulting in nausea and vomiting or dehydration, medication side effects, and inappropriate patient expectations (J Gastrointest Surg. 2016 Nov;20[11]:1797-1801).

“I think readmissions are a good outcome to study, because they incorporate many different elements of the patient experience, including patient safety and satisfaction. No surgeon wants to have a patient come back to the ER and be readmitted. And finally, there’s the cost,” Dr. Morton observed.

He noted that members of the MBSAQIP developed the DROP project in a highly efficient and cost-effective manner through a series of webinars and conference calls without the need for face-to-face meetings. The group plans to follow the same approach to its future quality improvement programs.

The DROP study was funded without industry support. Dr. Morton reported serving on advisory boards for Allurion and Novo Nordisk.

 

[email protected]

NEW ORLEANS – A significant reduction in 30-day all-cause hospital readmissions after sleeve gastrectomy was accomplished through the first-ever joint national quality improvement collaboration between the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery, John M. Morton, MD, reported at Obesity Week 2016.

The quality improvement program, known as DROP, for Decreasing Readmissions through Opportunities Provided, was developed by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). It was put to the test in a year-long study conducted in 128 nationally representative U.S. hospitals. The study involved a comparison of the participating hospitals’ 30-day all-cause readmission rates following bariatric surgery in the year prior to vs. the year after launch of the DROP project.

Bruce Jancin/Frontline Medical News

Overall, the 30-day all-cause readmission rate after primary laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, or laparoscopic Roux-en-Y gastric bypass dropped only modestly, from 4.76% to 4.61%, a relative reduction of 3.2%. But that’s not the whole story. Hidden within that modest overall result were major improvements, Dr. Morton said at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Of particular interest was the finding that the readmission rate following laparoscopic sleeve gastrectomy decreased from 4.02% to 3.54%, a 12% reduction. That’s an important finding, because sleeve gastrectomy is now by far the most frequently performed type of bariatric surgery in the United States. Indeed, it accounted for 54% of the estimated 196,000 bariatric surgery procedures performed in the country in 2015. Roux-en-Y gastric bypass was a distant second at 23%, followed by surgical revisions at 13.6%.

Moreover, the impact of the DROP initiative appeared to accelerate over time. The initiative as tested consisted of a comprehensive bundle of numerous components addressing preoperative, in-hospital, and postoperative care, and it took a while for hospitals to implement. The 30-day readmission rate following laparoscopic sleeve gastrectomy actually increased by 9.2% in the first 3 months following launch of the DROP initiative. But the readmission rate then took a U-turn, declining by 13.2% in the second quarter compared to the year-before rate, by 16.9% in the third quarter, and falling by 27.1% in the final 3 months of the study.

Mean length of stay for patients undergoing laparoscopic sleeve gastrectomy fell significantly, from 1.9 days pre-DROP to 1.79 days. The DROP intervention also achieved a significant decrease in length of stay for laparoscopic adjustable gastric banding, from 0.5 to 0.42 days.

The rate of readmission within 24 hours post discharge in laparoscopic sleeve gastrectomy patients decreased significantly by 19% after introduction of the DROP program. The trend was favorable, albeit not statistically significant, for the other two bariatric procedures studied.

Of note, hospitals in the two quartiles with the lowest preintervention 30-day all-cause readmission rates post bariatric surgery, with rates of 1.34% and 3.15%, respectively, didn’t derive any further reduction by participating in the DROP program. They already were performing many of the elements included in the intervention. But hospitals in the third quartile significantly improved their 30-day readmission rate from 4.84% to 4.13%, and those in the fourth quartile improved from 7.31% preintervention to 4.47% under the DROP program.

The program had no impact on postoperative leak rates or other surgical complications. However, patient satisfaction scores improved after introduction of the DROP intervention.

The preoperative components of the DROP readmission prevention bundle included a standardized 5-minute educational video featuring a surgeon, nutritionist, pharmacist, and psychologist or psychiatrist, with advice on key issues related to the upcoming operation. That’s also when the visits with the surgeon and a nutritionist were to be scheduled for within 30 days post surgery, and when the patient received phone numbers for the clinic and on-call surgeon in case questions arose later.

The in-hospital elements of the DROP intervention included provision of a clinical roadmap to guide patient expectations, as well as a nutritional consultation. The postoperative components included a day-after-discharge phone call from a nurse or physician assistant, a letter sent to the referring physician containing a discharge summary and recommendations, and a system to make sure that the scheduled follow-up appointments with the surgeon and nutritionist actually take place.

Since adherence to the various components of the DROP bundle varied from hospital to hospital, it was possible for Dr. Morton and his coinvestigators to determine which elements made the most difference in improving 30-day readmission rates. They found that the key difference makers were the nurse’s phone call on the day following discharge and the postoperative visits with the surgeon and nutritionist within the first several weeks.

Asked whether the study findings mean that hospitals that already have a 30-day all-cause readmission rate in the lower half of the national average don’t need to adopt the DROP program, Dr. Morton replied: “One size does not fit all. Maybe some centers don’t need to do all this.”

Thirty-day all-cause readmissions were selected for the first quality improvement project by the MBSAQIP in part because the Centers for Medicare & Medicaid Services has identified it as a priority area for surgery in general. Also, Dr. Morton was a coinvestigator in a study that found many readmissions after bariatric surgery are tied to preventable causes, including dietary indiscretions resulting in nausea and vomiting or dehydration, medication side effects, and inappropriate patient expectations (J Gastrointest Surg. 2016 Nov;20[11]:1797-1801).

“I think readmissions are a good outcome to study, because they incorporate many different elements of the patient experience, including patient safety and satisfaction. No surgeon wants to have a patient come back to the ER and be readmitted. And finally, there’s the cost,” Dr. Morton observed.

He noted that members of the MBSAQIP developed the DROP project in a highly efficient and cost-effective manner through a series of webinars and conference calls without the need for face-to-face meetings. The group plans to follow the same approach to its future quality improvement programs.

The DROP study was funded without industry support. Dr. Morton reported serving on advisory boards for Allurion and Novo Nordisk.

 

[email protected]

NEW ORLEANS – A significant reduction in 30-day all-cause hospital readmissions after sleeve gastrectomy was accomplished through the first-ever joint national quality improvement collaboration between the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery, John M. Morton, MD, reported at Obesity Week 2016.

The quality improvement program, known as DROP, for Decreasing Readmissions through Opportunities Provided, was developed by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). It was put to the test in a year-long study conducted in 128 nationally representative U.S. hospitals. The study involved a comparison of the participating hospitals’ 30-day all-cause readmission rates following bariatric surgery in the year prior to vs. the year after launch of the DROP project.

Bruce Jancin/Frontline Medical News

Overall, the 30-day all-cause readmission rate after primary laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, or laparoscopic Roux-en-Y gastric bypass dropped only modestly, from 4.76% to 4.61%, a relative reduction of 3.2%. But that’s not the whole story. Hidden within that modest overall result were major improvements, Dr. Morton said at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Of particular interest was the finding that the readmission rate following laparoscopic sleeve gastrectomy decreased from 4.02% to 3.54%, a 12% reduction. That’s an important finding, because sleeve gastrectomy is now by far the most frequently performed type of bariatric surgery in the United States. Indeed, it accounted for 54% of the estimated 196,000 bariatric surgery procedures performed in the country in 2015. Roux-en-Y gastric bypass was a distant second at 23%, followed by surgical revisions at 13.6%.

Moreover, the impact of the DROP initiative appeared to accelerate over time. The initiative as tested consisted of a comprehensive bundle of numerous components addressing preoperative, in-hospital, and postoperative care, and it took a while for hospitals to implement. The 30-day readmission rate following laparoscopic sleeve gastrectomy actually increased by 9.2% in the first 3 months following launch of the DROP initiative. But the readmission rate then took a U-turn, declining by 13.2% in the second quarter compared to the year-before rate, by 16.9% in the third quarter, and falling by 27.1% in the final 3 months of the study.

Mean length of stay for patients undergoing laparoscopic sleeve gastrectomy fell significantly, from 1.9 days pre-DROP to 1.79 days. The DROP intervention also achieved a significant decrease in length of stay for laparoscopic adjustable gastric banding, from 0.5 to 0.42 days.

The rate of readmission within 24 hours post discharge in laparoscopic sleeve gastrectomy patients decreased significantly by 19% after introduction of the DROP program. The trend was favorable, albeit not statistically significant, for the other two bariatric procedures studied.

Of note, hospitals in the two quartiles with the lowest preintervention 30-day all-cause readmission rates post bariatric surgery, with rates of 1.34% and 3.15%, respectively, didn’t derive any further reduction by participating in the DROP program. They already were performing many of the elements included in the intervention. But hospitals in the third quartile significantly improved their 30-day readmission rate from 4.84% to 4.13%, and those in the fourth quartile improved from 7.31% preintervention to 4.47% under the DROP program.

The program had no impact on postoperative leak rates or other surgical complications. However, patient satisfaction scores improved after introduction of the DROP intervention.

The preoperative components of the DROP readmission prevention bundle included a standardized 5-minute educational video featuring a surgeon, nutritionist, pharmacist, and psychologist or psychiatrist, with advice on key issues related to the upcoming operation. That’s also when the visits with the surgeon and a nutritionist were to be scheduled for within 30 days post surgery, and when the patient received phone numbers for the clinic and on-call surgeon in case questions arose later.

The in-hospital elements of the DROP intervention included provision of a clinical roadmap to guide patient expectations, as well as a nutritional consultation. The postoperative components included a day-after-discharge phone call from a nurse or physician assistant, a letter sent to the referring physician containing a discharge summary and recommendations, and a system to make sure that the scheduled follow-up appointments with the surgeon and nutritionist actually take place.

Since adherence to the various components of the DROP bundle varied from hospital to hospital, it was possible for Dr. Morton and his coinvestigators to determine which elements made the most difference in improving 30-day readmission rates. They found that the key difference makers were the nurse’s phone call on the day following discharge and the postoperative visits with the surgeon and nutritionist within the first several weeks.

Asked whether the study findings mean that hospitals that already have a 30-day all-cause readmission rate in the lower half of the national average don’t need to adopt the DROP program, Dr. Morton replied: “One size does not fit all. Maybe some centers don’t need to do all this.”

Thirty-day all-cause readmissions were selected for the first quality improvement project by the MBSAQIP in part because the Centers for Medicare & Medicaid Services has identified it as a priority area for surgery in general. Also, Dr. Morton was a coinvestigator in a study that found many readmissions after bariatric surgery are tied to preventable causes, including dietary indiscretions resulting in nausea and vomiting or dehydration, medication side effects, and inappropriate patient expectations (J Gastrointest Surg. 2016 Nov;20[11]:1797-1801).

“I think readmissions are a good outcome to study, because they incorporate many different elements of the patient experience, including patient safety and satisfaction. No surgeon wants to have a patient come back to the ER and be readmitted. And finally, there’s the cost,” Dr. Morton observed.

He noted that members of the MBSAQIP developed the DROP project in a highly efficient and cost-effective manner through a series of webinars and conference calls without the need for face-to-face meetings. The group plans to follow the same approach to its future quality improvement programs.

The DROP study was funded without industry support. Dr. Morton reported serving on advisory boards for Allurion and Novo Nordisk.

 

[email protected]

 

NEW ORLEANS – The first-ever analysis of medical malpractice closed claims involving bariatric surgeons spotlights key opportunities for improvement for the surgical specialty, Eric J. DeMaria, MD, declared at Obesity Week 2016.

Four of the nation’s largest medical malpractice insurance companies agreed to allow members of an American Society for Metabolic and Bariatric Surgery task force to make site visits to their corporate offices, where the surgeons sat in closed rooms to read and take notes on a total of 175 cases closed during 2010-2015. Those case notes were later shared with the full task force, which sifted through the details in order to identify common causal themes and opportunities for improvement, explained Dr. DeMaria, a bariatric surgeon in Suffolk, Va.

Bruce Jancin/Frontline Medical News

This first report at Obesity Week 2016 merely provides an overview of the group’s initial analysis of the data. The plan is for the task force to bring forth lessons learned and specific recommendations for improved patient safety to the full American Society for Metabolic and Bariatric Surgery membership over time, he said at the meeting, presented by the Obesity Society of America and the ASMBS.

Among the key findings:

• The defense prevailed in 63% of cases. The mean expense for defending a lawsuit was $91,836.

• In the 37% of cases involving monetary awards, the mean figure was $293,500, ranging from $20,000 to $8 million.

• Mortality was involved in 35% of cases. Other notable complications resulting in lawsuits included leak in 18% of cases, bowel obstruction in 10%, bleeding in 5.3%, retained foreign body in 5.3%, and vascular injury from access in 4.4%.

• Preoperative issues such as informed consent and disclosure of information were rare.

• The defendant surgeon was a foreign medical graduate in 27.5% of cases, board certified in 75.9%, and only 43% of the hospitals where the surgery took place were accredited. All those figures are at odds with national norms.

• The panel determined that the cause of the complication was provider-related in 50% of cases, system-related in 29%, and intrinsic to the patient’s disease in 21%.

• In the panel’s view, the complication was preventable by the surgeon in nearly 60% of cases and not preventable by the surgeon in 20%, with the remainder of cases deemed impossible to judge.

• Better preoperative care would have prevented the complication in 20% of cases, in the panel’s view. Better postoperative care would have prevented the complication in 45%.

• Just over 5% of the malpractice claims involved nonstandard malabsorptive operations. “Some of them I’d never heard of before,” according to Dr. DeMaria.

• Care was deemed by the panel to be appropriate in roughly 21% of the malpractice cases and grossly negligent or incompetent in 8%. Twenty-three percent of lawsuits involved preventable error of such magnitude that significant coaching and instruction would be required in order to prevent a recurrence.

Dr. DeMaria observed that this analysis of closed claims suggests that in order to reduce future malpractice claims against bariatric surgeons, it makes sense to focus on a few key areas of practice where most of the serious problems occur.

“We found the same themes repeated over and over; for example, delays in diagnosis and treatment of leaks,” he said.

A substantial number of the lawsuits could have been prevented through the use of preinsufflation and optical trocars, or access away from the midline, he added.

But the number one theme to emerge from the lawsuit analysis was poor communication with the health care team and/or family. The experts on the task force considered the communication performance to be appropriate in only 20% of cases.

“I would emphasize the strong contribution of communication issues, and the strong contribution of coverage and handoff issues,” Dr. DeMaria said. “One example of an intervention that might be introduced would be to standardize the language used in the operating room just before you start to staple the stomach, very similar to what airplane pilots do in their communication. We saw cases over and over again where the anesthesia person was asked to take out the [nasogastric] tube didn’t realize that meant the esophageal stethoscope, too.

“We need to do a better job of not just making sure a coverage person has been identified, but actually communicating with that person and doing a standardized handoff procedure,” Dr. DeMaria continued. “Management of postoperative phone calls is another important area: Who answers the phone? What are they supposed to do with that information? How do you get patients to appropriate care?”

Discussant Ramsey M. Dallal, MD, congratulated Dr. DeMaria and his fellow ASMBS task force members on “the massive amount of work” entailed in this project. And he urged his colleagues to take to heart the lessons learned.

“People hear the word ‘malpractice’ and they get fearful. They think of lawyers and of being attacked. The reality is this is not a malpractice study; this is a patient safety study. A study like this is an excellent way to improve patient safety. The problem with registry data is we don’t get the details – and it’s the case details that point out problems and potential solutions,” said Dr. Dallal, director of bariatrics and vice chair of the department of surgery at the Einstein Healthcare Network in the Philadelphia area.

The closed claims analysis was conducted free of commercial support. Dr. DeMaria reported serving as a consultant to Covidien and Ethicon.

 

[email protected]
 

 

NEW ORLEANS – The first-ever analysis of medical malpractice closed claims involving bariatric surgeons spotlights key opportunities for improvement for the surgical specialty, Eric J. DeMaria, MD, declared at Obesity Week 2016.

Four of the nation’s largest medical malpractice insurance companies agreed to allow members of an American Society for Metabolic and Bariatric Surgery task force to make site visits to their corporate offices, where the surgeons sat in closed rooms to read and take notes on a total of 175 cases closed during 2010-2015. Those case notes were later shared with the full task force, which sifted through the details in order to identify common causal themes and opportunities for improvement, explained Dr. DeMaria, a bariatric surgeon in Suffolk, Va.

Bruce Jancin/Frontline Medical News

This first report at Obesity Week 2016 merely provides an overview of the group’s initial analysis of the data. The plan is for the task force to bring forth lessons learned and specific recommendations for improved patient safety to the full American Society for Metabolic and Bariatric Surgery membership over time, he said at the meeting, presented by the Obesity Society of America and the ASMBS.

Among the key findings:

• The defense prevailed in 63% of cases. The mean expense for defending a lawsuit was $91,836.

• In the 37% of cases involving monetary awards, the mean figure was $293,500, ranging from $20,000 to $8 million.

• Mortality was involved in 35% of cases. Other notable complications resulting in lawsuits included leak in 18% of cases, bowel obstruction in 10%, bleeding in 5.3%, retained foreign body in 5.3%, and vascular injury from access in 4.4%.

• Preoperative issues such as informed consent and disclosure of information were rare.

• The defendant surgeon was a foreign medical graduate in 27.5% of cases, board certified in 75.9%, and only 43% of the hospitals where the surgery took place were accredited. All those figures are at odds with national norms.

• The panel determined that the cause of the complication was provider-related in 50% of cases, system-related in 29%, and intrinsic to the patient’s disease in 21%.

• In the panel’s view, the complication was preventable by the surgeon in nearly 60% of cases and not preventable by the surgeon in 20%, with the remainder of cases deemed impossible to judge.

• Better preoperative care would have prevented the complication in 20% of cases, in the panel’s view. Better postoperative care would have prevented the complication in 45%.

• Just over 5% of the malpractice claims involved nonstandard malabsorptive operations. “Some of them I’d never heard of before,” according to Dr. DeMaria.

• Care was deemed by the panel to be appropriate in roughly 21% of the malpractice cases and grossly negligent or incompetent in 8%. Twenty-three percent of lawsuits involved preventable error of such magnitude that significant coaching and instruction would be required in order to prevent a recurrence.

Dr. DeMaria observed that this analysis of closed claims suggests that in order to reduce future malpractice claims against bariatric surgeons, it makes sense to focus on a few key areas of practice where most of the serious problems occur.

“We found the same themes repeated over and over; for example, delays in diagnosis and treatment of leaks,” he said.

A substantial number of the lawsuits could have been prevented through the use of preinsufflation and optical trocars, or access away from the midline, he added.

But the number one theme to emerge from the lawsuit analysis was poor communication with the health care team and/or family. The experts on the task force considered the communication performance to be appropriate in only 20% of cases.

“I would emphasize the strong contribution of communication issues, and the strong contribution of coverage and handoff issues,” Dr. DeMaria said. “One example of an intervention that might be introduced would be to standardize the language used in the operating room just before you start to staple the stomach, very similar to what airplane pilots do in their communication. We saw cases over and over again where the anesthesia person was asked to take out the [nasogastric] tube didn’t realize that meant the esophageal stethoscope, too.

“We need to do a better job of not just making sure a coverage person has been identified, but actually communicating with that person and doing a standardized handoff procedure,” Dr. DeMaria continued. “Management of postoperative phone calls is another important area: Who answers the phone? What are they supposed to do with that information? How do you get patients to appropriate care?”

Discussant Ramsey M. Dallal, MD, congratulated Dr. DeMaria and his fellow ASMBS task force members on “the massive amount of work” entailed in this project. And he urged his colleagues to take to heart the lessons learned.

“People hear the word ‘malpractice’ and they get fearful. They think of lawyers and of being attacked. The reality is this is not a malpractice study; this is a patient safety study. A study like this is an excellent way to improve patient safety. The problem with registry data is we don’t get the details – and it’s the case details that point out problems and potential solutions,” said Dr. Dallal, director of bariatrics and vice chair of the department of surgery at the Einstein Healthcare Network in the Philadelphia area.

The closed claims analysis was conducted free of commercial support. Dr. DeMaria reported serving as a consultant to Covidien and Ethicon.

 

[email protected]
 

 

NEW ORLEANS – The first-ever analysis of medical malpractice closed claims involving bariatric surgeons spotlights key opportunities for improvement for the surgical specialty, Eric J. DeMaria, MD, declared at Obesity Week 2016.

Four of the nation’s largest medical malpractice insurance companies agreed to allow members of an American Society for Metabolic and Bariatric Surgery task force to make site visits to their corporate offices, where the surgeons sat in closed rooms to read and take notes on a total of 175 cases closed during 2010-2015. Those case notes were later shared with the full task force, which sifted through the details in order to identify common causal themes and opportunities for improvement, explained Dr. DeMaria, a bariatric surgeon in Suffolk, Va.

Bruce Jancin/Frontline Medical News

This first report at Obesity Week 2016 merely provides an overview of the group’s initial analysis of the data. The plan is for the task force to bring forth lessons learned and specific recommendations for improved patient safety to the full American Society for Metabolic and Bariatric Surgery membership over time, he said at the meeting, presented by the Obesity Society of America and the ASMBS.

Among the key findings:

• The defense prevailed in 63% of cases. The mean expense for defending a lawsuit was $91,836.

• In the 37% of cases involving monetary awards, the mean figure was $293,500, ranging from $20,000 to $8 million.

• Mortality was involved in 35% of cases. Other notable complications resulting in lawsuits included leak in 18% of cases, bowel obstruction in 10%, bleeding in 5.3%, retained foreign body in 5.3%, and vascular injury from access in 4.4%.

• Preoperative issues such as informed consent and disclosure of information were rare.

• The defendant surgeon was a foreign medical graduate in 27.5% of cases, board certified in 75.9%, and only 43% of the hospitals where the surgery took place were accredited. All those figures are at odds with national norms.

• The panel determined that the cause of the complication was provider-related in 50% of cases, system-related in 29%, and intrinsic to the patient’s disease in 21%.

• In the panel’s view, the complication was preventable by the surgeon in nearly 60% of cases and not preventable by the surgeon in 20%, with the remainder of cases deemed impossible to judge.

• Better preoperative care would have prevented the complication in 20% of cases, in the panel’s view. Better postoperative care would have prevented the complication in 45%.

• Just over 5% of the malpractice claims involved nonstandard malabsorptive operations. “Some of them I’d never heard of before,” according to Dr. DeMaria.

• Care was deemed by the panel to be appropriate in roughly 21% of the malpractice cases and grossly negligent or incompetent in 8%. Twenty-three percent of lawsuits involved preventable error of such magnitude that significant coaching and instruction would be required in order to prevent a recurrence.

Dr. DeMaria observed that this analysis of closed claims suggests that in order to reduce future malpractice claims against bariatric surgeons, it makes sense to focus on a few key areas of practice where most of the serious problems occur.

“We found the same themes repeated over and over; for example, delays in diagnosis and treatment of leaks,” he said.

A substantial number of the lawsuits could have been prevented through the use of preinsufflation and optical trocars, or access away from the midline, he added.

But the number one theme to emerge from the lawsuit analysis was poor communication with the health care team and/or family. The experts on the task force considered the communication performance to be appropriate in only 20% of cases.

“I would emphasize the strong contribution of communication issues, and the strong contribution of coverage and handoff issues,” Dr. DeMaria said. “One example of an intervention that might be introduced would be to standardize the language used in the operating room just before you start to staple the stomach, very similar to what airplane pilots do in their communication. We saw cases over and over again where the anesthesia person was asked to take out the [nasogastric] tube didn’t realize that meant the esophageal stethoscope, too.

“We need to do a better job of not just making sure a coverage person has been identified, but actually communicating with that person and doing a standardized handoff procedure,” Dr. DeMaria continued. “Management of postoperative phone calls is another important area: Who answers the phone? What are they supposed to do with that information? How do you get patients to appropriate care?”

Discussant Ramsey M. Dallal, MD, congratulated Dr. DeMaria and his fellow ASMBS task force members on “the massive amount of work” entailed in this project. And he urged his colleagues to take to heart the lessons learned.

“People hear the word ‘malpractice’ and they get fearful. They think of lawyers and of being attacked. The reality is this is not a malpractice study; this is a patient safety study. A study like this is an excellent way to improve patient safety. The problem with registry data is we don’t get the details – and it’s the case details that point out problems and potential solutions,” said Dr. Dallal, director of bariatrics and vice chair of the department of surgery at the Einstein Healthcare Network in the Philadelphia area.

The closed claims analysis was conducted free of commercial support. Dr. DeMaria reported serving as a consultant to Covidien and Ethicon.

 

[email protected]
 

NEW ORLEANS – The widespread health insurance industry practice of requiring obese patients to spend months on a physician-supervised strict weight-loss diet prior to approving coverage of bariatric surgery accomplishes nothing constructive, Charles J. Keith Jr., MD, reported at Obesity Week 2016.

“We found that insurance-mandated preoperative diets were associated with a significant delay in treatment, no improvement in postoperative complication rates, and also no improvement in weight loss outcomes. If anything, after adjusting for potential confounding variables, the outcomes were inferior to the group that wasn’t required to diet,” said Dr. Keith of the University of Alabama at Birmingham.

Bruce Jancin/Frontline Medical News

He added that there is no Class I evidence to show that the requirement for a physician-supervised lengthy preoperative diet program results in improved weight loss outcomes, so the rationale for this mandate is not science based.

Dr. Keith presented a retrospective review from the prospectively collected Alabama University bariatric surgery database, which included all 284 patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy during 2009-2013. A total of 79% of the patients had private health insurance that required their participation in a preoperative physician-guided diet program, typically for 6 months. The other 21% did not have a mandatory preoperative diet requirement; the great majority of this group were covered under Medicare, which doesn’t require a diet program before bariatric surgery. The two groups weren’t significantly different in initial or immediately preoperative weight or body mass index, obesity-related comorbid conditions, type of bariatric surgery, or socioeconomic status.

The mean time from initial clinic visit to bariatric surgery was significantly shorter in the group with no mandated preoperative diet, at 154 vs. 218 days. In a multivariate analysis adjusted for age, sex, race, operation type, and comorbidities, the no-mandatory-diet group had a significantly greater reduction in BMI 6 months post surgery: a mean loss of 12.2 kg/m², compared with 10.9 kg/m² in the group required to participate in a preoperative diet. The difference was even greater at 2 years follow-up: a mean decrease of 14.9 kg/m² in the no-diet group, vs. 10.7 kg/m² in the mandatory diet group. The no-diet group experienced a mean 33% weight loss at 2 years, significantly better than the 25% weight loss in the mandatory diet group, Dr. Keith reported at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Audience discussion showed that the insurance-mandated preoperative diet requirement is a hot button issue in the bariatric surgical community.

“I think these insurance programs are specifically designed to delay care,” one surgeon asserted.

Another bariatric surgeon commented that while Dr. Keith’s study will be helpful in advocating for removal of the mandatory preoperative diet requirement, what’s really needed are studies that demonstrate just how often this requirement results in drop out from bariatric programs by patients who’ve grown discouraged by yet-another unsuccessful attempt at nonsurgical weight loss.

Dr. Keith reported having no financial conflicts of interest regarding his study.
 

[email protected]


 

NEW ORLEANS – The widespread health insurance industry practice of requiring obese patients to spend months on a physician-supervised strict weight-loss diet prior to approving coverage of bariatric surgery accomplishes nothing constructive, Charles J. Keith Jr., MD, reported at Obesity Week 2016.

“We found that insurance-mandated preoperative diets were associated with a significant delay in treatment, no improvement in postoperative complication rates, and also no improvement in weight loss outcomes. If anything, after adjusting for potential confounding variables, the outcomes were inferior to the group that wasn’t required to diet,” said Dr. Keith of the University of Alabama at Birmingham.

Bruce Jancin/Frontline Medical News

He added that there is no Class I evidence to show that the requirement for a physician-supervised lengthy preoperative diet program results in improved weight loss outcomes, so the rationale for this mandate is not science based.

Dr. Keith presented a retrospective review from the prospectively collected Alabama University bariatric surgery database, which included all 284 patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy during 2009-2013. A total of 79% of the patients had private health insurance that required their participation in a preoperative physician-guided diet program, typically for 6 months. The other 21% did not have a mandatory preoperative diet requirement; the great majority of this group were covered under Medicare, which doesn’t require a diet program before bariatric surgery. The two groups weren’t significantly different in initial or immediately preoperative weight or body mass index, obesity-related comorbid conditions, type of bariatric surgery, or socioeconomic status.

The mean time from initial clinic visit to bariatric surgery was significantly shorter in the group with no mandated preoperative diet, at 154 vs. 218 days. In a multivariate analysis adjusted for age, sex, race, operation type, and comorbidities, the no-mandatory-diet group had a significantly greater reduction in BMI 6 months post surgery: a mean loss of 12.2 kg/m², compared with 10.9 kg/m² in the group required to participate in a preoperative diet. The difference was even greater at 2 years follow-up: a mean decrease of 14.9 kg/m² in the no-diet group, vs. 10.7 kg/m² in the mandatory diet group. The no-diet group experienced a mean 33% weight loss at 2 years, significantly better than the 25% weight loss in the mandatory diet group, Dr. Keith reported at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Audience discussion showed that the insurance-mandated preoperative diet requirement is a hot button issue in the bariatric surgical community.

“I think these insurance programs are specifically designed to delay care,” one surgeon asserted.

Another bariatric surgeon commented that while Dr. Keith’s study will be helpful in advocating for removal of the mandatory preoperative diet requirement, what’s really needed are studies that demonstrate just how often this requirement results in drop out from bariatric programs by patients who’ve grown discouraged by yet-another unsuccessful attempt at nonsurgical weight loss.

Dr. Keith reported having no financial conflicts of interest regarding his study.
 

[email protected]


 

NEW ORLEANS – The widespread health insurance industry practice of requiring obese patients to spend months on a physician-supervised strict weight-loss diet prior to approving coverage of bariatric surgery accomplishes nothing constructive, Charles J. Keith Jr., MD, reported at Obesity Week 2016.

“We found that insurance-mandated preoperative diets were associated with a significant delay in treatment, no improvement in postoperative complication rates, and also no improvement in weight loss outcomes. If anything, after adjusting for potential confounding variables, the outcomes were inferior to the group that wasn’t required to diet,” said Dr. Keith of the University of Alabama at Birmingham.

Bruce Jancin/Frontline Medical News

He added that there is no Class I evidence to show that the requirement for a physician-supervised lengthy preoperative diet program results in improved weight loss outcomes, so the rationale for this mandate is not science based.

Dr. Keith presented a retrospective review from the prospectively collected Alabama University bariatric surgery database, which included all 284 patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy during 2009-2013. A total of 79% of the patients had private health insurance that required their participation in a preoperative physician-guided diet program, typically for 6 months. The other 21% did not have a mandatory preoperative diet requirement; the great majority of this group were covered under Medicare, which doesn’t require a diet program before bariatric surgery. The two groups weren’t significantly different in initial or immediately preoperative weight or body mass index, obesity-related comorbid conditions, type of bariatric surgery, or socioeconomic status.

The mean time from initial clinic visit to bariatric surgery was significantly shorter in the group with no mandated preoperative diet, at 154 vs. 218 days. In a multivariate analysis adjusted for age, sex, race, operation type, and comorbidities, the no-mandatory-diet group had a significantly greater reduction in BMI 6 months post surgery: a mean loss of 12.2 kg/m², compared with 10.9 kg/m² in the group required to participate in a preoperative diet. The difference was even greater at 2 years follow-up: a mean decrease of 14.9 kg/m² in the no-diet group, vs. 10.7 kg/m² in the mandatory diet group. The no-diet group experienced a mean 33% weight loss at 2 years, significantly better than the 25% weight loss in the mandatory diet group, Dr. Keith reported at the meeting, presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Audience discussion showed that the insurance-mandated preoperative diet requirement is a hot button issue in the bariatric surgical community.

“I think these insurance programs are specifically designed to delay care,” one surgeon asserted.

Another bariatric surgeon commented that while Dr. Keith’s study will be helpful in advocating for removal of the mandatory preoperative diet requirement, what’s really needed are studies that demonstrate just how often this requirement results in drop out from bariatric programs by patients who’ve grown discouraged by yet-another unsuccessful attempt at nonsurgical weight loss.

Dr. Keith reported having no financial conflicts of interest regarding his study.
 

[email protected]


 

VIENNA – What a difference a decade can make in the world of psychiatry.

Take, for example, the case of 3,4-methylenedioxymethamphetamine, better known as MDMA or, when used recreationally, as ecstasy, the love drug.

“Ten years ago at pretty much every scientific meeting where MDMA was being discussed, people were looking to find problems with it. People were dredging around trying to vilify this drug, because there was a hope that it might cause brain damage, which would justify having made its use illicit. Ten years later, we’ve changed direction completely, from fear and hating MDMA to loving it. Now we’re talking about the possibility that MDMA might actually heal the brain, and restoring MDMA to the therapeutic armamentarium,” David Nutt, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/Frontline Medical News

Indeed, the drug’s potential as an adjunct to psychotherapy in patients with posttraumatic stress disorder was the topic of a packed-to-the-gills session in the largest hall at the ECNP Congress, where Dr. Nutt highlighted recent insights into the psychopharmacology of MDMA and other speakers described evidence of the drug’s salutary effects on autobiographical memory and social cognition.

“The biggest problem with MDMA is its name,” quipped Dr. Nutt, professor of neuropsychopharmacology at Imperial College London.

“It used to be called ‘empathy,’ but when it started being used recreationally at raves and in the clubs, the dealers decided to change its name to ‘ecstasy.’ And that created havoc, because there’s nothing that aged editors of newspapers hate more than young people having ecstasy. They hated the term, and so the drug had to go,” according to the psychiatrist.

MDMA’s comeback as a potentially valuable medication in psychiatry can be traced to the first report of the drug’s impressive success when used as an adjunct to psychotherapy in a randomized, placebo-controlled pilot study. Michael C. Mithoefer, MD, a psychiatrist in private practice in South Carolina, and his coinvestigators stunned the psychiatric world by reporting that 10 of 12 patients with chronic PTSD refractory to both medications and psychotherapy showed significant clinical improvement in response to just two sessions of MDMA-assisted psychotherapy supplementing a more conventional course of psychotherapy (J Psychopharmacology. 2011 Apr;25[4]:439-52).

Moreover, the benefits proved durable: In a subsequent paper, the investigators reported the clinical benefit of this two-dose treatment program persisted at a mean 3.8 years of follow-up and no safety concerns had been seen (J Psychopharmacol. 2013 Jan;27[1]:28-39).

This study, which eventually drew the attention of military veterans’ groups with political clout, proved hugely influential, especially since PTSD is so common and often is highly treatment resistant.

“We’re now living in a very strange world where trauma has in some ways become the No. 1 problem facing many societies,” Dr. Nutt observed.

He predicted that with the Food and Drug Administration’s recent approval of clinical trials of MDMA in patients with PTSD, the drug will be licensed for that indication “within the next couple years.”
 

How MDMA works

The pharmacology of MDMA is complex, he continued. The drug is chiefly a serotonin-releasing agent and 5HT reuptake blocker, but it also acts as an agonist on alpha-adrenergic receptors, has muscarinic and histamine-blocking effects, and promotes release of oxytocin.

Animal studies have demonstrated that MDMA facilitates extinction of fear memories through a mechanism involving changes in levels of brain-derived neurotrophic factor. Experience in humans has shown that the drug has diverse pro-social effects: It is activating, enhances mood, promotes more flexible thinking, boosts tactile experiences, and increases empathy, which in turn aids patients in bonding with their therapists.

Dr. Nutt and his coinvestigators performed the first whole-brain study of the effects of MDMA using functional MRI. This double-blind, placebo-controlled, crossover study in healthy volunteers used measurements obtained through arterial spin labeling and analysis of blood oxygen level–dependent resting state functional connectivity. The investigators documented that the marked increase in positive mood and decreased magnitude of negative personal memories produced by MDMA was accompanied by profound reduction of cerebral blood flow in the right amygdala and hippocampus. Cerebral blood flow also was reduced in the right medial temporal lobe, thalamus, and inferior visual cortex. MDMA also resulted in decreased amygdala-cortical connectivity (Biol Psychiatry. 2015 Oct 15;78[8]:554-62; Int J Neuropsychopharmacol. 2014 Apr;17[4]:527-40).

The changes in those particular brain systems are consistent with and most likely underlie the drug’s therapeutic effects, he said. Taken together, they could serve to assist a patient in re-engaging with traumatic memories with less interference from emotional centers, thereby helping to gain executive control of the memory of the trauma.

H. Valerie Curran, PhD, a coinvestigator in the brain imaging study, cautioned the rapt audience that while there are abundant favorable anecdotal reports from psychotherapists going back as far as the 1970s, the actual evidence base for MDMA as a therapeutic adjunct to psychotherapy for PTSD is still pretty thin. She noted that in their groundbreaking study, Dr. Mithoefer and his colleagues used an unconventional form of psychotherapy modeled on the LSD therapy developed by Stanislav Grof, MD, PhD. The two MDMA-assisted sessions were each 8 hours long and included shamanistic techniques and specialized breathing to promote diminished oxygen to the brain. Also, the patient sat on a futon listening to music with a male therapist on one side and a female therapist on the other. As a clinical psychologist herself, she assured the audience that this is not standard practice in her field.

Only one other randomized, double-blind, placebo-controlled study of MDMA-assisted psychotherapy has been published to date (J Psychopharmacol. 2013 Jan;27[1]:40-52). With just 12 participants, it was too small to be conclusive. So there is a definite need for additional controlled studies on the interaction between MDMA and evidence-based forms of psychotherapy. Fortunately, additional clinical trials are ongoing, noted Dr. Curran, professor of psychopharmacology at University College London.

She presented highlights of a study she and her coinvestigators carried out to determine how MDMA affects the encoding and recall of emotional autobiographical memories, since the core of most psychotherapy for PTSD entails controlled revisiting of traumatic memories. The nonblinded study included a group of recreational MDMA users who – on two separate occasions, one under the influence of street-quality MDMA of uncertain dose and purity, the other on placebo – were tasked with responding to self-threatening scenarios, exposure to compassionate imagery, and a large series of positive and negative adjectives addressed at themselves or another person (J Psychopharmacol. 2015 Sep;29[9]:961-70).

The investigators found that MDMA enhanced the emotional intensity, vividness, and positivity of the subjects’ best autobiographical memories while modestly reducing the negativity of their worst memories. Structured ratings of compassion markedly increased while on MDMA. Overall, the drug’s effects were similar to those obtained through rigorous cognitive training methods developed in venerable Eastern contemplative practices in pursuit of a compassionate mindset, according to Dr. Curran.

The study results suggest a mechanism by which MDMA might enhance psychotherapy not only by improving the therapeutic alliance but also by reducing self-referential emotional processing without diminishing declarative memory, she added.
 

 

Findings of Swiss studies

Matthias E. Liechti, MD, head of the psychopharmacology research unit at the University of Basel, explained that at present Switzerland is the only country in the world where it’s legal to prescribe MDMA. Ditto LSD. Psychiatrists can do so on a case-by-case basis outside of a clinical trial setting in patients with treatment-resistant PTSD or anxiety disorders.

Dr. Liechti and his coinvestigators are interested in examining how MDMA affects social cognition as assessed by outcome measures, including a structured face emotion recognition test, the multifaceted empathy test, and a sexual arousal task.

Bruce Jancin/Frontline Medical News

In a series of studies in which they exposed subjects to MDMA, alcohol, methamphetamine, or LSD, they have established that both MDMA and LSD produce empathogenic effects that are possibly serotonin mediated. On a visual analog scale, subjects on those drugs gave high marks for feeling happy, open, trusting, and extroverted, and having a sense of well-being. MDMA impaired recognition of fearful, angry, and sad faces.

In contrast, methamphetamine, a pure stimulant that activates the norepinephrine/dopamine system, produced no empathogenic effects, but it enhanced recognition of sad or fearful faces. Alcohol slightly increased self-ratings for trust, happiness, and openness.

Methamphetamine increased ratings of sexual arousal in response to explicit sexual stimuli, while MDMA had no effect on sexual arousal.

MDMA and LSD increased oxytocin, prolactin, and cortisol levels consistent with their serotonergic effects. Methylphenidate did not, Dr. Liechti said.

A neuroscientist in the audience raised a possible safety concern regarding MDMA: If the drug has an agonist effect on serotonin receptors, couldn’t it have cardiac side effects similar to those of fenfluramine, a drug now banned because it stimulated the abundant 5HT-2b receptors present in the heart, resulting in increased risk of pulmonary hypertension and other adverse cardiovascular effects?

Dr. Nutt replied that there are multitudes of serotonin receptor subtypes, and it’s not yet known whether MDMA acts upon the 5HT-2b receptor. In any case, it shouldn’t be an issue for the drug’s medicinal use.

“Luckily, the effects of MDMA wear off quickly, and when it’s used with psychotherapy we may be giving only one or two doses in a lifetime, so it shouldn’t be a concern,” he said.

Dr. Nutt reported that the functional MRI brain imaging study was funded by a British television station and a private foundation.

“The reason for that is we’ve found it impossible to get any money from any traditional government funders to study drugs like MDMA unless you write grants to show they’re harmful,” he asserted.

Dr. Curran reported having no financial conflicts of interest regarding her studies. Dr. Liechti’s work is supported by the Swiss National Science Foundation.

[email protected]

VIENNA – What a difference a decade can make in the world of psychiatry.

Take, for example, the case of 3,4-methylenedioxymethamphetamine, better known as MDMA or, when used recreationally, as ecstasy, the love drug.

“Ten years ago at pretty much every scientific meeting where MDMA was being discussed, people were looking to find problems with it. People were dredging around trying to vilify this drug, because there was a hope that it might cause brain damage, which would justify having made its use illicit. Ten years later, we’ve changed direction completely, from fear and hating MDMA to loving it. Now we’re talking about the possibility that MDMA might actually heal the brain, and restoring MDMA to the therapeutic armamentarium,” David Nutt, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/Frontline Medical News

Indeed, the drug’s potential as an adjunct to psychotherapy in patients with posttraumatic stress disorder was the topic of a packed-to-the-gills session in the largest hall at the ECNP Congress, where Dr. Nutt highlighted recent insights into the psychopharmacology of MDMA and other speakers described evidence of the drug’s salutary effects on autobiographical memory and social cognition.

“The biggest problem with MDMA is its name,” quipped Dr. Nutt, professor of neuropsychopharmacology at Imperial College London.

“It used to be called ‘empathy,’ but when it started being used recreationally at raves and in the clubs, the dealers decided to change its name to ‘ecstasy.’ And that created havoc, because there’s nothing that aged editors of newspapers hate more than young people having ecstasy. They hated the term, and so the drug had to go,” according to the psychiatrist.

MDMA’s comeback as a potentially valuable medication in psychiatry can be traced to the first report of the drug’s impressive success when used as an adjunct to psychotherapy in a randomized, placebo-controlled pilot study. Michael C. Mithoefer, MD, a psychiatrist in private practice in South Carolina, and his coinvestigators stunned the psychiatric world by reporting that 10 of 12 patients with chronic PTSD refractory to both medications and psychotherapy showed significant clinical improvement in response to just two sessions of MDMA-assisted psychotherapy supplementing a more conventional course of psychotherapy (J Psychopharmacology. 2011 Apr;25[4]:439-52).

Moreover, the benefits proved durable: In a subsequent paper, the investigators reported the clinical benefit of this two-dose treatment program persisted at a mean 3.8 years of follow-up and no safety concerns had been seen (J Psychopharmacol. 2013 Jan;27[1]:28-39).

This study, which eventually drew the attention of military veterans’ groups with political clout, proved hugely influential, especially since PTSD is so common and often is highly treatment resistant.

“We’re now living in a very strange world where trauma has in some ways become the No. 1 problem facing many societies,” Dr. Nutt observed.

He predicted that with the Food and Drug Administration’s recent approval of clinical trials of MDMA in patients with PTSD, the drug will be licensed for that indication “within the next couple years.”
 

How MDMA works

The pharmacology of MDMA is complex, he continued. The drug is chiefly a serotonin-releasing agent and 5HT reuptake blocker, but it also acts as an agonist on alpha-adrenergic receptors, has muscarinic and histamine-blocking effects, and promotes release of oxytocin.

Animal studies have demonstrated that MDMA facilitates extinction of fear memories through a mechanism involving changes in levels of brain-derived neurotrophic factor. Experience in humans has shown that the drug has diverse pro-social effects: It is activating, enhances mood, promotes more flexible thinking, boosts tactile experiences, and increases empathy, which in turn aids patients in bonding with their therapists.

Dr. Nutt and his coinvestigators performed the first whole-brain study of the effects of MDMA using functional MRI. This double-blind, placebo-controlled, crossover study in healthy volunteers used measurements obtained through arterial spin labeling and analysis of blood oxygen level–dependent resting state functional connectivity. The investigators documented that the marked increase in positive mood and decreased magnitude of negative personal memories produced by MDMA was accompanied by profound reduction of cerebral blood flow in the right amygdala and hippocampus. Cerebral blood flow also was reduced in the right medial temporal lobe, thalamus, and inferior visual cortex. MDMA also resulted in decreased amygdala-cortical connectivity (Biol Psychiatry. 2015 Oct 15;78[8]:554-62; Int J Neuropsychopharmacol. 2014 Apr;17[4]:527-40).

The changes in those particular brain systems are consistent with and most likely underlie the drug’s therapeutic effects, he said. Taken together, they could serve to assist a patient in re-engaging with traumatic memories with less interference from emotional centers, thereby helping to gain executive control of the memory of the trauma.

H. Valerie Curran, PhD, a coinvestigator in the brain imaging study, cautioned the rapt audience that while there are abundant favorable anecdotal reports from psychotherapists going back as far as the 1970s, the actual evidence base for MDMA as a therapeutic adjunct to psychotherapy for PTSD is still pretty thin. She noted that in their groundbreaking study, Dr. Mithoefer and his colleagues used an unconventional form of psychotherapy modeled on the LSD therapy developed by Stanislav Grof, MD, PhD. The two MDMA-assisted sessions were each 8 hours long and included shamanistic techniques and specialized breathing to promote diminished oxygen to the brain. Also, the patient sat on a futon listening to music with a male therapist on one side and a female therapist on the other. As a clinical psychologist herself, she assured the audience that this is not standard practice in her field.

Only one other randomized, double-blind, placebo-controlled study of MDMA-assisted psychotherapy has been published to date (J Psychopharmacol. 2013 Jan;27[1]:40-52). With just 12 participants, it was too small to be conclusive. So there is a definite need for additional controlled studies on the interaction between MDMA and evidence-based forms of psychotherapy. Fortunately, additional clinical trials are ongoing, noted Dr. Curran, professor of psychopharmacology at University College London.

She presented highlights of a study she and her coinvestigators carried out to determine how MDMA affects the encoding and recall of emotional autobiographical memories, since the core of most psychotherapy for PTSD entails controlled revisiting of traumatic memories. The nonblinded study included a group of recreational MDMA users who – on two separate occasions, one under the influence of street-quality MDMA of uncertain dose and purity, the other on placebo – were tasked with responding to self-threatening scenarios, exposure to compassionate imagery, and a large series of positive and negative adjectives addressed at themselves or another person (J Psychopharmacol. 2015 Sep;29[9]:961-70).

The investigators found that MDMA enhanced the emotional intensity, vividness, and positivity of the subjects’ best autobiographical memories while modestly reducing the negativity of their worst memories. Structured ratings of compassion markedly increased while on MDMA. Overall, the drug’s effects were similar to those obtained through rigorous cognitive training methods developed in venerable Eastern contemplative practices in pursuit of a compassionate mindset, according to Dr. Curran.

The study results suggest a mechanism by which MDMA might enhance psychotherapy not only by improving the therapeutic alliance but also by reducing self-referential emotional processing without diminishing declarative memory, she added.
 

 

Findings of Swiss studies

Matthias E. Liechti, MD, head of the psychopharmacology research unit at the University of Basel, explained that at present Switzerland is the only country in the world where it’s legal to prescribe MDMA. Ditto LSD. Psychiatrists can do so on a case-by-case basis outside of a clinical trial setting in patients with treatment-resistant PTSD or anxiety disorders.

Dr. Liechti and his coinvestigators are interested in examining how MDMA affects social cognition as assessed by outcome measures, including a structured face emotion recognition test, the multifaceted empathy test, and a sexual arousal task.

Bruce Jancin/Frontline Medical News

In a series of studies in which they exposed subjects to MDMA, alcohol, methamphetamine, or LSD, they have established that both MDMA and LSD produce empathogenic effects that are possibly serotonin mediated. On a visual analog scale, subjects on those drugs gave high marks for feeling happy, open, trusting, and extroverted, and having a sense of well-being. MDMA impaired recognition of fearful, angry, and sad faces.

In contrast, methamphetamine, a pure stimulant that activates the norepinephrine/dopamine system, produced no empathogenic effects, but it enhanced recognition of sad or fearful faces. Alcohol slightly increased self-ratings for trust, happiness, and openness.

Methamphetamine increased ratings of sexual arousal in response to explicit sexual stimuli, while MDMA had no effect on sexual arousal.

MDMA and LSD increased oxytocin, prolactin, and cortisol levels consistent with their serotonergic effects. Methylphenidate did not, Dr. Liechti said.

A neuroscientist in the audience raised a possible safety concern regarding MDMA: If the drug has an agonist effect on serotonin receptors, couldn’t it have cardiac side effects similar to those of fenfluramine, a drug now banned because it stimulated the abundant 5HT-2b receptors present in the heart, resulting in increased risk of pulmonary hypertension and other adverse cardiovascular effects?

Dr. Nutt replied that there are multitudes of serotonin receptor subtypes, and it’s not yet known whether MDMA acts upon the 5HT-2b receptor. In any case, it shouldn’t be an issue for the drug’s medicinal use.

“Luckily, the effects of MDMA wear off quickly, and when it’s used with psychotherapy we may be giving only one or two doses in a lifetime, so it shouldn’t be a concern,” he said.

Dr. Nutt reported that the functional MRI brain imaging study was funded by a British television station and a private foundation.

“The reason for that is we’ve found it impossible to get any money from any traditional government funders to study drugs like MDMA unless you write grants to show they’re harmful,” he asserted.

Dr. Curran reported having no financial conflicts of interest regarding her studies. Dr. Liechti’s work is supported by the Swiss National Science Foundation.

[email protected]

VIENNA – What a difference a decade can make in the world of psychiatry.

Take, for example, the case of 3,4-methylenedioxymethamphetamine, better known as MDMA or, when used recreationally, as ecstasy, the love drug.

“Ten years ago at pretty much every scientific meeting where MDMA was being discussed, people were looking to find problems with it. People were dredging around trying to vilify this drug, because there was a hope that it might cause brain damage, which would justify having made its use illicit. Ten years later, we’ve changed direction completely, from fear and hating MDMA to loving it. Now we’re talking about the possibility that MDMA might actually heal the brain, and restoring MDMA to the therapeutic armamentarium,” David Nutt, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/Frontline Medical News

Indeed, the drug’s potential as an adjunct to psychotherapy in patients with posttraumatic stress disorder was the topic of a packed-to-the-gills session in the largest hall at the ECNP Congress, where Dr. Nutt highlighted recent insights into the psychopharmacology of MDMA and other speakers described evidence of the drug’s salutary effects on autobiographical memory and social cognition.

“The biggest problem with MDMA is its name,” quipped Dr. Nutt, professor of neuropsychopharmacology at Imperial College London.

“It used to be called ‘empathy,’ but when it started being used recreationally at raves and in the clubs, the dealers decided to change its name to ‘ecstasy.’ And that created havoc, because there’s nothing that aged editors of newspapers hate more than young people having ecstasy. They hated the term, and so the drug had to go,” according to the psychiatrist.

MDMA’s comeback as a potentially valuable medication in psychiatry can be traced to the first report of the drug’s impressive success when used as an adjunct to psychotherapy in a randomized, placebo-controlled pilot study. Michael C. Mithoefer, MD, a psychiatrist in private practice in South Carolina, and his coinvestigators stunned the psychiatric world by reporting that 10 of 12 patients with chronic PTSD refractory to both medications and psychotherapy showed significant clinical improvement in response to just two sessions of MDMA-assisted psychotherapy supplementing a more conventional course of psychotherapy (J Psychopharmacology. 2011 Apr;25[4]:439-52).

Moreover, the benefits proved durable: In a subsequent paper, the investigators reported the clinical benefit of this two-dose treatment program persisted at a mean 3.8 years of follow-up and no safety concerns had been seen (J Psychopharmacol. 2013 Jan;27[1]:28-39).

This study, which eventually drew the attention of military veterans’ groups with political clout, proved hugely influential, especially since PTSD is so common and often is highly treatment resistant.

“We’re now living in a very strange world where trauma has in some ways become the No. 1 problem facing many societies,” Dr. Nutt observed.

He predicted that with the Food and Drug Administration’s recent approval of clinical trials of MDMA in patients with PTSD, the drug will be licensed for that indication “within the next couple years.”
 

How MDMA works

The pharmacology of MDMA is complex, he continued. The drug is chiefly a serotonin-releasing agent and 5HT reuptake blocker, but it also acts as an agonist on alpha-adrenergic receptors, has muscarinic and histamine-blocking effects, and promotes release of oxytocin.

Animal studies have demonstrated that MDMA facilitates extinction of fear memories through a mechanism involving changes in levels of brain-derived neurotrophic factor. Experience in humans has shown that the drug has diverse pro-social effects: It is activating, enhances mood, promotes more flexible thinking, boosts tactile experiences, and increases empathy, which in turn aids patients in bonding with their therapists.

Dr. Nutt and his coinvestigators performed the first whole-brain study of the effects of MDMA using functional MRI. This double-blind, placebo-controlled, crossover study in healthy volunteers used measurements obtained through arterial spin labeling and analysis of blood oxygen level–dependent resting state functional connectivity. The investigators documented that the marked increase in positive mood and decreased magnitude of negative personal memories produced by MDMA was accompanied by profound reduction of cerebral blood flow in the right amygdala and hippocampus. Cerebral blood flow also was reduced in the right medial temporal lobe, thalamus, and inferior visual cortex. MDMA also resulted in decreased amygdala-cortical connectivity (Biol Psychiatry. 2015 Oct 15;78[8]:554-62; Int J Neuropsychopharmacol. 2014 Apr;17[4]:527-40).

The changes in those particular brain systems are consistent with and most likely underlie the drug’s therapeutic effects, he said. Taken together, they could serve to assist a patient in re-engaging with traumatic memories with less interference from emotional centers, thereby helping to gain executive control of the memory of the trauma.

H. Valerie Curran, PhD, a coinvestigator in the brain imaging study, cautioned the rapt audience that while there are abundant favorable anecdotal reports from psychotherapists going back as far as the 1970s, the actual evidence base for MDMA as a therapeutic adjunct to psychotherapy for PTSD is still pretty thin. She noted that in their groundbreaking study, Dr. Mithoefer and his colleagues used an unconventional form of psychotherapy modeled on the LSD therapy developed by Stanislav Grof, MD, PhD. The two MDMA-assisted sessions were each 8 hours long and included shamanistic techniques and specialized breathing to promote diminished oxygen to the brain. Also, the patient sat on a futon listening to music with a male therapist on one side and a female therapist on the other. As a clinical psychologist herself, she assured the audience that this is not standard practice in her field.

Only one other randomized, double-blind, placebo-controlled study of MDMA-assisted psychotherapy has been published to date (J Psychopharmacol. 2013 Jan;27[1]:40-52). With just 12 participants, it was too small to be conclusive. So there is a definite need for additional controlled studies on the interaction between MDMA and evidence-based forms of psychotherapy. Fortunately, additional clinical trials are ongoing, noted Dr. Curran, professor of psychopharmacology at University College London.

She presented highlights of a study she and her coinvestigators carried out to determine how MDMA affects the encoding and recall of emotional autobiographical memories, since the core of most psychotherapy for PTSD entails controlled revisiting of traumatic memories. The nonblinded study included a group of recreational MDMA users who – on two separate occasions, one under the influence of street-quality MDMA of uncertain dose and purity, the other on placebo – were tasked with responding to self-threatening scenarios, exposure to compassionate imagery, and a large series of positive and negative adjectives addressed at themselves or another person (J Psychopharmacol. 2015 Sep;29[9]:961-70).

The investigators found that MDMA enhanced the emotional intensity, vividness, and positivity of the subjects’ best autobiographical memories while modestly reducing the negativity of their worst memories. Structured ratings of compassion markedly increased while on MDMA. Overall, the drug’s effects were similar to those obtained through rigorous cognitive training methods developed in venerable Eastern contemplative practices in pursuit of a compassionate mindset, according to Dr. Curran.

The study results suggest a mechanism by which MDMA might enhance psychotherapy not only by improving the therapeutic alliance but also by reducing self-referential emotional processing without diminishing declarative memory, she added.
 

 

Findings of Swiss studies

Matthias E. Liechti, MD, head of the psychopharmacology research unit at the University of Basel, explained that at present Switzerland is the only country in the world where it’s legal to prescribe MDMA. Ditto LSD. Psychiatrists can do so on a case-by-case basis outside of a clinical trial setting in patients with treatment-resistant PTSD or anxiety disorders.

Dr. Liechti and his coinvestigators are interested in examining how MDMA affects social cognition as assessed by outcome measures, including a structured face emotion recognition test, the multifaceted empathy test, and a sexual arousal task.

Bruce Jancin/Frontline Medical News

In a series of studies in which they exposed subjects to MDMA, alcohol, methamphetamine, or LSD, they have established that both MDMA and LSD produce empathogenic effects that are possibly serotonin mediated. On a visual analog scale, subjects on those drugs gave high marks for feeling happy, open, trusting, and extroverted, and having a sense of well-being. MDMA impaired recognition of fearful, angry, and sad faces.

In contrast, methamphetamine, a pure stimulant that activates the norepinephrine/dopamine system, produced no empathogenic effects, but it enhanced recognition of sad or fearful faces. Alcohol slightly increased self-ratings for trust, happiness, and openness.

Methamphetamine increased ratings of sexual arousal in response to explicit sexual stimuli, while MDMA had no effect on sexual arousal.

MDMA and LSD increased oxytocin, prolactin, and cortisol levels consistent with their serotonergic effects. Methylphenidate did not, Dr. Liechti said.

A neuroscientist in the audience raised a possible safety concern regarding MDMA: If the drug has an agonist effect on serotonin receptors, couldn’t it have cardiac side effects similar to those of fenfluramine, a drug now banned because it stimulated the abundant 5HT-2b receptors present in the heart, resulting in increased risk of pulmonary hypertension and other adverse cardiovascular effects?

Dr. Nutt replied that there are multitudes of serotonin receptor subtypes, and it’s not yet known whether MDMA acts upon the 5HT-2b receptor. In any case, it shouldn’t be an issue for the drug’s medicinal use.

“Luckily, the effects of MDMA wear off quickly, and when it’s used with psychotherapy we may be giving only one or two doses in a lifetime, so it shouldn’t be a concern,” he said.

Dr. Nutt reported that the functional MRI brain imaging study was funded by a British television station and a private foundation.

“The reason for that is we’ve found it impossible to get any money from any traditional government funders to study drugs like MDMA unless you write grants to show they’re harmful,” he asserted.

Dr. Curran reported having no financial conflicts of interest regarding her studies. Dr. Liechti’s work is supported by the Swiss National Science Foundation.

[email protected]

 

The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.

In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.

©Doug Menuez/thinkstockphotos.com

In Washington State, the perceived harmfulness of marijuana declined by 14.2% among 8th graders and 16.1% among 10th graders after legalization, while marijuana use in the previous 30-day period increased by 2% and 4.1%. Over the same period in states that did not legalize, perceived harmfulness decreased by 4.9% among 8th graders and 7.2% among 10th graders, while marijuana use actually decreased by 1.3% and 0.9%. The differences between the 8th and 10th grades in Washington vs. the nonlegalized states were statistically significant (JAMA Pediatr. 2016. Dec 27. doi:10.1001/jamapediatrics.2016.3624).

“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”

Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.

The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.

Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.

Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.

Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.

The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.

[email protected]
 

 

The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.

In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.

©Doug Menuez/thinkstockphotos.com

In Washington State, the perceived harmfulness of marijuana declined by 14.2% among 8th graders and 16.1% among 10th graders after legalization, while marijuana use in the previous 30-day period increased by 2% and 4.1%. Over the same period in states that did not legalize, perceived harmfulness decreased by 4.9% among 8th graders and 7.2% among 10th graders, while marijuana use actually decreased by 1.3% and 0.9%. The differences between the 8th and 10th grades in Washington vs. the nonlegalized states were statistically significant (JAMA Pediatr. 2016. Dec 27. doi:10.1001/jamapediatrics.2016.3624).

“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”

Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.

The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.

Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.

Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.

Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.

The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.

[email protected]
 

 

The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.

In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.

©Doug Menuez/thinkstockphotos.com

In Washington State, the perceived harmfulness of marijuana declined by 14.2% among 8th graders and 16.1% among 10th graders after legalization, while marijuana use in the previous 30-day period increased by 2% and 4.1%. Over the same period in states that did not legalize, perceived harmfulness decreased by 4.9% among 8th graders and 7.2% among 10th graders, while marijuana use actually decreased by 1.3% and 0.9%. The differences between the 8th and 10th grades in Washington vs. the nonlegalized states were statistically significant (JAMA Pediatr. 2016. Dec 27. doi:10.1001/jamapediatrics.2016.3624).

“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”

Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.

The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.

Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.

Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.

Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.

The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.

[email protected]
 

Results of a phase 3 trial suggest a 3-drug combination improves survival in newly diagnosed multiple myeloma (MM).

The trial showed that bortezomib, lenalidomide, and dexamethasone (VRd) could significantly

improve progression-free and overall survival when compared to lenalidomide and dexamethasone (Rd).

In addition, investigators said the risk-benefit profile of VRd was acceptable.

The team noted, however, that grade 3 or higher neurologic adverse events (AEs) were more common with VRd than with Rd.

“Our results are clear,” said principal investigator Brian G.M. Durie, MD, of Cedars-Sinai Outpatient Cancer Center in Los Angeles, California.

“Using bortezomib in combination with lenalidomide and dexamethasone in frontline treatment—hitting the disease early and hard—makes a meaningful difference for myeloma patients. Our results represent a potential new standard of care.”

Dr Durie and his colleagues reported the results of this trial in The Lancet.

The research was funded by Millennium Pharmaceuticals, Takeda Oncology Company, Celgene Corporation, the National Institutes of Health, the National Cancer Institute, and the National Clinical Trial Network.

The trial enrolled 525 adults with MM. The patients ranged in age from 28 to 87, had active MM, and had not had any prior treatment for their disease.

The patients were randomized to 2 treatment groups. One group received Rd for 6 cycles over 6 months. The other group received VRd for 8 cycles over 6 months.

Results

The median follow-up was 55 months. In the VRd group, 241 patients were evaluable for safety and 216 for response. In the Rd group, 226 patients were evaluable for safety and 214 for response.

The overall response rate was 82% (176/216) in the VRd group and 72% (153/214) in the Rd group. The complete response rates were 16% (34/216) and 8% (18/214), respectively.

The median progression-free survival was 43 months in the VRd group and 30 months in the Rd group. The hazard ratio was 0.712 (P=0.0018).

The median overall survival was 75 months in the VRd group and 64 months in the Rd group. The hazard ratio was 0.709 (P=0.025).

The rate of grade 3 or higher AEs was 82% in the VRd group and 75% in the Rd group. The rate of discontinuation due to AEs was 23% and 10%, respectively.

Grade 3 or higher neurologic AEs were more frequent in the VRd group than in the Rd group—33% and 11%, respectively (P<0.0001).

There were 2 treatment-related deaths in the VRd group but none in the Rd group. And 10 patients in each group had a second primary malignancy.

“This is a landmark study that lends clarity to frontline therapy of myeloma,” said study author S. Vincent Rajkumar, MD, of Mayo Clinic in Rochester, Minnesota.

“Newer alternatives to VRd may be more expensive, cumbersome, or toxic. These regimens will therefore need to show superiority over VRd in randomized trials.”

Also worth noting, Dr Rajkumar said, is that the VRd regimen will become even more cost-effective as the drugs in this combination become generic over time.

Results of a phase 3 trial suggest a 3-drug combination improves survival in newly diagnosed multiple myeloma (MM).

The trial showed that bortezomib, lenalidomide, and dexamethasone (VRd) could significantly

improve progression-free and overall survival when compared to lenalidomide and dexamethasone (Rd).

In addition, investigators said the risk-benefit profile of VRd was acceptable.

The team noted, however, that grade 3 or higher neurologic adverse events (AEs) were more common with VRd than with Rd.

“Our results are clear,” said principal investigator Brian G.M. Durie, MD, of Cedars-Sinai Outpatient Cancer Center in Los Angeles, California.

“Using bortezomib in combination with lenalidomide and dexamethasone in frontline treatment—hitting the disease early and hard—makes a meaningful difference for myeloma patients. Our results represent a potential new standard of care.”

Dr Durie and his colleagues reported the results of this trial in The Lancet.

The research was funded by Millennium Pharmaceuticals, Takeda Oncology Company, Celgene Corporation, the National Institutes of Health, the National Cancer Institute, and the National Clinical Trial Network.

The trial enrolled 525 adults with MM. The patients ranged in age from 28 to 87, had active MM, and had not had any prior treatment for their disease.

The patients were randomized to 2 treatment groups. One group received Rd for 6 cycles over 6 months. The other group received VRd for 8 cycles over 6 months.

Results

The median follow-up was 55 months. In the VRd group, 241 patients were evaluable for safety and 216 for response. In the Rd group, 226 patients were evaluable for safety and 214 for response.

The overall response rate was 82% (176/216) in the VRd group and 72% (153/214) in the Rd group. The complete response rates were 16% (34/216) and 8% (18/214), respectively.

The median progression-free survival was 43 months in the VRd group and 30 months in the Rd group. The hazard ratio was 0.712 (P=0.0018).

The median overall survival was 75 months in the VRd group and 64 months in the Rd group. The hazard ratio was 0.709 (P=0.025).

The rate of grade 3 or higher AEs was 82% in the VRd group and 75% in the Rd group. The rate of discontinuation due to AEs was 23% and 10%, respectively.

Grade 3 or higher neurologic AEs were more frequent in the VRd group than in the Rd group—33% and 11%, respectively (P<0.0001).

There were 2 treatment-related deaths in the VRd group but none in the Rd group. And 10 patients in each group had a second primary malignancy.

“This is a landmark study that lends clarity to frontline therapy of myeloma,” said study author S. Vincent Rajkumar, MD, of Mayo Clinic in Rochester, Minnesota.

“Newer alternatives to VRd may be more expensive, cumbersome, or toxic. These regimens will therefore need to show superiority over VRd in randomized trials.”

Also worth noting, Dr Rajkumar said, is that the VRd regimen will become even more cost-effective as the drugs in this combination become generic over time.

Results of a phase 3 trial suggest a 3-drug combination improves survival in newly diagnosed multiple myeloma (MM).

The trial showed that bortezomib, lenalidomide, and dexamethasone (VRd) could significantly

improve progression-free and overall survival when compared to lenalidomide and dexamethasone (Rd).

In addition, investigators said the risk-benefit profile of VRd was acceptable.

The team noted, however, that grade 3 or higher neurologic adverse events (AEs) were more common with VRd than with Rd.

“Our results are clear,” said principal investigator Brian G.M. Durie, MD, of Cedars-Sinai Outpatient Cancer Center in Los Angeles, California.

“Using bortezomib in combination with lenalidomide and dexamethasone in frontline treatment—hitting the disease early and hard—makes a meaningful difference for myeloma patients. Our results represent a potential new standard of care.”

Dr Durie and his colleagues reported the results of this trial in The Lancet.

The research was funded by Millennium Pharmaceuticals, Takeda Oncology Company, Celgene Corporation, the National Institutes of Health, the National Cancer Institute, and the National Clinical Trial Network.

The trial enrolled 525 adults with MM. The patients ranged in age from 28 to 87, had active MM, and had not had any prior treatment for their disease.

The patients were randomized to 2 treatment groups. One group received Rd for 6 cycles over 6 months. The other group received VRd for 8 cycles over 6 months.

Results

The median follow-up was 55 months. In the VRd group, 241 patients were evaluable for safety and 216 for response. In the Rd group, 226 patients were evaluable for safety and 214 for response.

The overall response rate was 82% (176/216) in the VRd group and 72% (153/214) in the Rd group. The complete response rates were 16% (34/216) and 8% (18/214), respectively.

The median progression-free survival was 43 months in the VRd group and 30 months in the Rd group. The hazard ratio was 0.712 (P=0.0018).

The median overall survival was 75 months in the VRd group and 64 months in the Rd group. The hazard ratio was 0.709 (P=0.025).

The rate of grade 3 or higher AEs was 82% in the VRd group and 75% in the Rd group. The rate of discontinuation due to AEs was 23% and 10%, respectively.

Grade 3 or higher neurologic AEs were more frequent in the VRd group than in the Rd group—33% and 11%, respectively (P<0.0001).

There were 2 treatment-related deaths in the VRd group but none in the Rd group. And 10 patients in each group had a second primary malignancy.

“This is a landmark study that lends clarity to frontline therapy of myeloma,” said study author S. Vincent Rajkumar, MD, of Mayo Clinic in Rochester, Minnesota.

“Newer alternatives to VRd may be more expensive, cumbersome, or toxic. These regimens will therefore need to show superiority over VRd in randomized trials.”

Also worth noting, Dr Rajkumar said, is that the VRd regimen will become even more cost-effective as the drugs in this combination become generic over time.

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

An anti-hypertensive drug can improve the effects of chelation therapy in patients with thalassemia major and cardiac iron overload, according to research published in Blood.

Researchers found that administering the drug, amlodipine, in conjunction with conventional chelation therapy significantly reduced myocardial iron concentration (MIC) in patients with cardiac iron overload at baseline, when compared to chelation therapy alone.

In addition, amlodipine did not cause any serious adverse events.

“The drug has been used clinically for decades and is considered safe for adults and children,” said study author Juliano de Lara Fernandes, MD, PhD, of José Michel Kalaf Research Institute in Campinas, São Paulo State, Brazil.

“As an adjunct to standard treatment, it can be greatly beneficial to patients and has few side effects.”

Dr Fernandes said he and his colleagues decided to test amlodipine in patients with thalassemia major because although chelation therapy works well in peripheral organs, it’s difficult to remove iron from the heart.

“Myocardial dysfunctions are currently the main cause of death among patients with thalassemia and can emerge in children from the age of 10,” Dr Fernandes said.

The most serious problem of all, he added, is caused by an accumulation of non-transferrin bound iron (NTBI) in myocardial cells. NTBI enters and leaves the liver without causing much damage to the organ, but it enters the heart via a channel whose main role is to carry calcium into cells.

“It occurred to us that drugs capable of blocking the calcium channel could also prevent NTBI from entering the heart and therefore increase the efficacy of chelation therapy,” Dr Fernandes said.

He and his colleagues tested this hypothesis in 62 patients with thalassemia major. The patients were divided into 2 treatment groups. One group received conventional chelation therapy along with amlodipine (5 mg/day), and the other received chelation therapy plus oral placebo.

Patients were further divided according to cardiac iron levels at baseline. Cardiac iron overload was defined as T2* < 35 ms. Fifty percent of patients in the amlodipine arm and 52% of those in the placebo arm had cardiac iron overload at baseline.

Results

The study’s main outcome was change in MIC, as determined by magnetic resonance imaging at 12 months.

At that point, among patients with cardiac iron overload at baseline, there was a significant decrease in MIC in the amlodipine arm but not the placebo arm. The median change in MIC was -0.26 mg/g and 0.01 mg/g, respectively (P=0.02).

The median MIC in the amlodipine arm went from 1.31 mg/g at baseline to 1.05 mg/g at 12 months (P=0.02). The median MIC in the placebo arm went from 0.77 mg/g at baseline to 0.75 at 12 months (P=0.76).

“Myocardial iron concentration fell 21% in patients with initial iron overload who were treated with chelation plus amlodipine, whereas it increased by 2% in those with initial overload who were treated with chelation plus placebo,” Dr Fernandes said.

On the other hand, there were no significant differences in MIC from baseline to 12 months among patients who received amlodipine but did not have cardiac iron overload at baseline.

For patients without cardiac iron overload at baseline, the median change in MIC was +0.04 mg/g in the amlodipine arm and -0.01 in the placebo arm (P=0.07).

The median MIC in the amlodipine arm went from 0.54 mg/g at baseline to 0.55 mg/g at 12 months. The median MIC in the placebo arm went from 0.55 mg/g at baseline to 0.52 mg/g at 12 months.

 

“Perhaps we would have needed to monitor these patients for a longer period to see the benefits of preventive therapy with amlodipine for people who don’t have excess iron in their organs,” Dr Fernandes said.

“For those who do, however, the results show it’s worth using amlodipine. There’s no need to change the existing therapy. It’s enough to administer the anti-hypertensive orally every day.”

There were 4 mild adverse events in the amlodipine arm but none in the placebo arm (13% vs 0%, P=0.11).

Three patients (10%) in the amlodipine arm had their initial dose of 5 mg/day reduced to 2.5 mg/day because of mild ankle edema (n=2) and dizziness (n=1). One patient had a mild cutaneous allergic reaction and stopped receiving amlodipine after 15 days but continued on study.

There were no deaths or hospital admissions due to cardiovascular complications during the trial.

An anti-hypertensive drug can improve the effects of chelation therapy in patients with thalassemia major and cardiac iron overload, according to research published in Blood.

Researchers found that administering the drug, amlodipine, in conjunction with conventional chelation therapy significantly reduced myocardial iron concentration (MIC) in patients with cardiac iron overload at baseline, when compared to chelation therapy alone.

In addition, amlodipine did not cause any serious adverse events.

“The drug has been used clinically for decades and is considered safe for adults and children,” said study author Juliano de Lara Fernandes, MD, PhD, of José Michel Kalaf Research Institute in Campinas, São Paulo State, Brazil.

“As an adjunct to standard treatment, it can be greatly beneficial to patients and has few side effects.”

Dr Fernandes said he and his colleagues decided to test amlodipine in patients with thalassemia major because although chelation therapy works well in peripheral organs, it’s difficult to remove iron from the heart.

“Myocardial dysfunctions are currently the main cause of death among patients with thalassemia and can emerge in children from the age of 10,” Dr Fernandes said.

The most serious problem of all, he added, is caused by an accumulation of non-transferrin bound iron (NTBI) in myocardial cells. NTBI enters and leaves the liver without causing much damage to the organ, but it enters the heart via a channel whose main role is to carry calcium into cells.

“It occurred to us that drugs capable of blocking the calcium channel could also prevent NTBI from entering the heart and therefore increase the efficacy of chelation therapy,” Dr Fernandes said.

He and his colleagues tested this hypothesis in 62 patients with thalassemia major. The patients were divided into 2 treatment groups. One group received conventional chelation therapy along with amlodipine (5 mg/day), and the other received chelation therapy plus oral placebo.

Patients were further divided according to cardiac iron levels at baseline. Cardiac iron overload was defined as T2* < 35 ms. Fifty percent of patients in the amlodipine arm and 52% of those in the placebo arm had cardiac iron overload at baseline.

Results

The study’s main outcome was change in MIC, as determined by magnetic resonance imaging at 12 months.

At that point, among patients with cardiac iron overload at baseline, there was a significant decrease in MIC in the amlodipine arm but not the placebo arm. The median change in MIC was -0.26 mg/g and 0.01 mg/g, respectively (P=0.02).

The median MIC in the amlodipine arm went from 1.31 mg/g at baseline to 1.05 mg/g at 12 months (P=0.02). The median MIC in the placebo arm went from 0.77 mg/g at baseline to 0.75 at 12 months (P=0.76).

“Myocardial iron concentration fell 21% in patients with initial iron overload who were treated with chelation plus amlodipine, whereas it increased by 2% in those with initial overload who were treated with chelation plus placebo,” Dr Fernandes said.

On the other hand, there were no significant differences in MIC from baseline to 12 months among patients who received amlodipine but did not have cardiac iron overload at baseline.

For patients without cardiac iron overload at baseline, the median change in MIC was +0.04 mg/g in the amlodipine arm and -0.01 in the placebo arm (P=0.07).

The median MIC in the amlodipine arm went from 0.54 mg/g at baseline to 0.55 mg/g at 12 months. The median MIC in the placebo arm went from 0.55 mg/g at baseline to 0.52 mg/g at 12 months.

 

“Perhaps we would have needed to monitor these patients for a longer period to see the benefits of preventive therapy with amlodipine for people who don’t have excess iron in their organs,” Dr Fernandes said.

“For those who do, however, the results show it’s worth using amlodipine. There’s no need to change the existing therapy. It’s enough to administer the anti-hypertensive orally every day.”

There were 4 mild adverse events in the amlodipine arm but none in the placebo arm (13% vs 0%, P=0.11).

Three patients (10%) in the amlodipine arm had their initial dose of 5 mg/day reduced to 2.5 mg/day because of mild ankle edema (n=2) and dizziness (n=1). One patient had a mild cutaneous allergic reaction and stopped receiving amlodipine after 15 days but continued on study.

There were no deaths or hospital admissions due to cardiovascular complications during the trial.

An anti-hypertensive drug can improve the effects of chelation therapy in patients with thalassemia major and cardiac iron overload, according to research published in Blood.

Researchers found that administering the drug, amlodipine, in conjunction with conventional chelation therapy significantly reduced myocardial iron concentration (MIC) in patients with cardiac iron overload at baseline, when compared to chelation therapy alone.

In addition, amlodipine did not cause any serious adverse events.

“The drug has been used clinically for decades and is considered safe for adults and children,” said study author Juliano de Lara Fernandes, MD, PhD, of José Michel Kalaf Research Institute in Campinas, São Paulo State, Brazil.

“As an adjunct to standard treatment, it can be greatly beneficial to patients and has few side effects.”

Dr Fernandes said he and his colleagues decided to test amlodipine in patients with thalassemia major because although chelation therapy works well in peripheral organs, it’s difficult to remove iron from the heart.

“Myocardial dysfunctions are currently the main cause of death among patients with thalassemia and can emerge in children from the age of 10,” Dr Fernandes said.

The most serious problem of all, he added, is caused by an accumulation of non-transferrin bound iron (NTBI) in myocardial cells. NTBI enters and leaves the liver without causing much damage to the organ, but it enters the heart via a channel whose main role is to carry calcium into cells.

“It occurred to us that drugs capable of blocking the calcium channel could also prevent NTBI from entering the heart and therefore increase the efficacy of chelation therapy,” Dr Fernandes said.

He and his colleagues tested this hypothesis in 62 patients with thalassemia major. The patients were divided into 2 treatment groups. One group received conventional chelation therapy along with amlodipine (5 mg/day), and the other received chelation therapy plus oral placebo.

Patients were further divided according to cardiac iron levels at baseline. Cardiac iron overload was defined as T2* < 35 ms. Fifty percent of patients in the amlodipine arm and 52% of those in the placebo arm had cardiac iron overload at baseline.

Results

The study’s main outcome was change in MIC, as determined by magnetic resonance imaging at 12 months.

At that point, among patients with cardiac iron overload at baseline, there was a significant decrease in MIC in the amlodipine arm but not the placebo arm. The median change in MIC was -0.26 mg/g and 0.01 mg/g, respectively (P=0.02).

The median MIC in the amlodipine arm went from 1.31 mg/g at baseline to 1.05 mg/g at 12 months (P=0.02). The median MIC in the placebo arm went from 0.77 mg/g at baseline to 0.75 at 12 months (P=0.76).

“Myocardial iron concentration fell 21% in patients with initial iron overload who were treated with chelation plus amlodipine, whereas it increased by 2% in those with initial overload who were treated with chelation plus placebo,” Dr Fernandes said.

On the other hand, there were no significant differences in MIC from baseline to 12 months among patients who received amlodipine but did not have cardiac iron overload at baseline.

For patients without cardiac iron overload at baseline, the median change in MIC was +0.04 mg/g in the amlodipine arm and -0.01 in the placebo arm (P=0.07).

The median MIC in the amlodipine arm went from 0.54 mg/g at baseline to 0.55 mg/g at 12 months. The median MIC in the placebo arm went from 0.55 mg/g at baseline to 0.52 mg/g at 12 months.

 

“Perhaps we would have needed to monitor these patients for a longer period to see the benefits of preventive therapy with amlodipine for people who don’t have excess iron in their organs,” Dr Fernandes said.

“For those who do, however, the results show it’s worth using amlodipine. There’s no need to change the existing therapy. It’s enough to administer the anti-hypertensive orally every day.”

There were 4 mild adverse events in the amlodipine arm but none in the placebo arm (13% vs 0%, P=0.11).

Three patients (10%) in the amlodipine arm had their initial dose of 5 mg/day reduced to 2.5 mg/day because of mild ankle edema (n=2) and dizziness (n=1). One patient had a mild cutaneous allergic reaction and stopped receiving amlodipine after 15 days but continued on study.

There were no deaths or hospital admissions due to cardiovascular complications during the trial.