Clinical question: Does total knee replacement followed by a 12-week non-surgical treatment program provide greater pain relief and improvement in function and quality of life than non-surgical treatment alone?

Background: The number of total knee replacements in the U.S. has increased dramatically since the 1970s and is expected to continue to rise. To date, evidence to support the effectiveness of surgical intervention compared to non-surgical intervention is lacking.

Study design: Randomized, controlled trial.

Setting: Aalborg University Hospital Outpatient Clinics, Denmark.

Synopsis: One hundred patients with osteoarthritis were randomly assigned to undergo total knee replacement followed by 12 weeks of non-surgical treatment or to receive only 12 weeks of non-surgical treatment. The non-surgical treatment program consisted of exercise, education, dietary advice, insoles, and pain medication. Change from baseline to 12 months was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

The total knee replacement group had a significantly greater improvement in the KOOS score than did the non-surgical group. Serious adverse events were more common in the total knee replacement group.

The study did not include a sham-surgery control group. It is unknown whether the KOOS pain subscale is generalizable to patients with severe pain. Additionally, the intensity of non-surgical treatment may have differed between groups.

Bottom line: Total knee replacement followed by non-surgical treatment is more efficacious than non-surgical treatment alone in providing pain relief and improving function and quality of life, but it is associated with higher number of adverse events.

Citation: Skou ST, Roos EM, Laursen MB, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373(17):1597-1606.

Clinical question: Does total knee replacement followed by a 12-week non-surgical treatment program provide greater pain relief and improvement in function and quality of life than non-surgical treatment alone?

Background: The number of total knee replacements in the U.S. has increased dramatically since the 1970s and is expected to continue to rise. To date, evidence to support the effectiveness of surgical intervention compared to non-surgical intervention is lacking.

Study design: Randomized, controlled trial.

Setting: Aalborg University Hospital Outpatient Clinics, Denmark.

Synopsis: One hundred patients with osteoarthritis were randomly assigned to undergo total knee replacement followed by 12 weeks of non-surgical treatment or to receive only 12 weeks of non-surgical treatment. The non-surgical treatment program consisted of exercise, education, dietary advice, insoles, and pain medication. Change from baseline to 12 months was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

The total knee replacement group had a significantly greater improvement in the KOOS score than did the non-surgical group. Serious adverse events were more common in the total knee replacement group.

The study did not include a sham-surgery control group. It is unknown whether the KOOS pain subscale is generalizable to patients with severe pain. Additionally, the intensity of non-surgical treatment may have differed between groups.

Bottom line: Total knee replacement followed by non-surgical treatment is more efficacious than non-surgical treatment alone in providing pain relief and improving function and quality of life, but it is associated with higher number of adverse events.

Citation: Skou ST, Roos EM, Laursen MB, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373(17):1597-1606.

Clinical question: Does total knee replacement followed by a 12-week non-surgical treatment program provide greater pain relief and improvement in function and quality of life than non-surgical treatment alone?

Background: The number of total knee replacements in the U.S. has increased dramatically since the 1970s and is expected to continue to rise. To date, evidence to support the effectiveness of surgical intervention compared to non-surgical intervention is lacking.

Study design: Randomized, controlled trial.

Setting: Aalborg University Hospital Outpatient Clinics, Denmark.

Synopsis: One hundred patients with osteoarthritis were randomly assigned to undergo total knee replacement followed by 12 weeks of non-surgical treatment or to receive only 12 weeks of non-surgical treatment. The non-surgical treatment program consisted of exercise, education, dietary advice, insoles, and pain medication. Change from baseline to 12 months was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

The total knee replacement group had a significantly greater improvement in the KOOS score than did the non-surgical group. Serious adverse events were more common in the total knee replacement group.

The study did not include a sham-surgery control group. It is unknown whether the KOOS pain subscale is generalizable to patients with severe pain. Additionally, the intensity of non-surgical treatment may have differed between groups.

Bottom line: Total knee replacement followed by non-surgical treatment is more efficacious than non-surgical treatment alone in providing pain relief and improving function and quality of life, but it is associated with higher number of adverse events.

Citation: Skou ST, Roos EM, Laursen MB, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373(17):1597-1606.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of a small study suggest that adolescent and young adult (AYA) cancer survivors have a range of concerns regarding their fertility.

The female cancer survivors studied were more likely than males to describe feeling distressed and overwhelmed about their fertility.

Females also tended to worry about pregnancy-related health risks and cancer recurrence.

However, AYA cancer survivors of both sexes expressed concerns about genetic risk factors and how infertility might impact their future lives.

Catherine Benedict, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, and her colleagues conducted this research and reported the results in the Journal of Adolescent and Young Adult Oncology.

The researchers assessed fertility concerns in 43 AYA cancer survivors. They were 16 to 24 at the time of the study, had been diagnosed with cancer between ages 14 and 18, and were at least 6 months post-treatment.

The subjects either completed an individual interview (n=26) or participated in 1 of 4 focus groups (n=17).

Before treatment, 5 of the males had banked sperm, but none of the females took steps to preserve their fertility. More males (50%) than females (39%) reported uncertainty about their fertility.

The researchers identified 3 themes when discussing fertility with the study subjects: fertility concerns, emotions raised when discussing fertility, and strategies used to manage fertility concerns.

Concerns

Some subjects expressed concerns about how potential infertility could affect dating and relationships with partners (8% of males and 20% of females).

Some subjects were concerned about the health risks associated with having children—both risks to the subjects themselves and to any potential children (39% of males and 30% of females).

And some subjects were concerned about how potential infertility would affect their lives going forward (31% of males and 20% of females).

Emotions

When it came to emotions associated with fertility discussions, some subjects said they felt distressed and overwhelmed (23% of males and 30% of females).

However, some subjects said they weren’t concerned about their fertility (31% of males and 15% of females) or they felt hopeful despite the risk of infertility (8% of males and 20% of females).

Managing concerns

The subjects also mentioned a few strategies for managing fertility concerns. Some said they had accepted infertility (23% of males and 15% of females).

Some subjects said they weren’t going to worry about their fertility until they were older and actually wanted to have children (23% of males and 20% of females).

And some subjects said they would rely on assisted reproductive technology if necessary (31% of males and 20% of females).

Dr Benedict and her colleagues said this study suggests AYA cancer survivors may have a number of reproductive concerns and fertility-related distress, which may affect other areas of psychosocial functioning.

So future research should explore how to best incorporate fertility-related informational and support services more fully into survivorship care.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of a small study suggest that adolescent and young adult (AYA) cancer survivors have a range of concerns regarding their fertility.

The female cancer survivors studied were more likely than males to describe feeling distressed and overwhelmed about their fertility.

Females also tended to worry about pregnancy-related health risks and cancer recurrence.

However, AYA cancer survivors of both sexes expressed concerns about genetic risk factors and how infertility might impact their future lives.

Catherine Benedict, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, and her colleagues conducted this research and reported the results in the Journal of Adolescent and Young Adult Oncology.

The researchers assessed fertility concerns in 43 AYA cancer survivors. They were 16 to 24 at the time of the study, had been diagnosed with cancer between ages 14 and 18, and were at least 6 months post-treatment.

The subjects either completed an individual interview (n=26) or participated in 1 of 4 focus groups (n=17).

Before treatment, 5 of the males had banked sperm, but none of the females took steps to preserve their fertility. More males (50%) than females (39%) reported uncertainty about their fertility.

The researchers identified 3 themes when discussing fertility with the study subjects: fertility concerns, emotions raised when discussing fertility, and strategies used to manage fertility concerns.

Concerns

Some subjects expressed concerns about how potential infertility could affect dating and relationships with partners (8% of males and 20% of females).

Some subjects were concerned about the health risks associated with having children—both risks to the subjects themselves and to any potential children (39% of males and 30% of females).

And some subjects were concerned about how potential infertility would affect their lives going forward (31% of males and 20% of females).

Emotions

When it came to emotions associated with fertility discussions, some subjects said they felt distressed and overwhelmed (23% of males and 30% of females).

However, some subjects said they weren’t concerned about their fertility (31% of males and 15% of females) or they felt hopeful despite the risk of infertility (8% of males and 20% of females).

Managing concerns

The subjects also mentioned a few strategies for managing fertility concerns. Some said they had accepted infertility (23% of males and 15% of females).

Some subjects said they weren’t going to worry about their fertility until they were older and actually wanted to have children (23% of males and 20% of females).

And some subjects said they would rely on assisted reproductive technology if necessary (31% of males and 20% of females).

Dr Benedict and her colleagues said this study suggests AYA cancer survivors may have a number of reproductive concerns and fertility-related distress, which may affect other areas of psychosocial functioning.

So future research should explore how to best incorporate fertility-related informational and support services more fully into survivorship care.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of a small study suggest that adolescent and young adult (AYA) cancer survivors have a range of concerns regarding their fertility.

The female cancer survivors studied were more likely than males to describe feeling distressed and overwhelmed about their fertility.

Females also tended to worry about pregnancy-related health risks and cancer recurrence.

However, AYA cancer survivors of both sexes expressed concerns about genetic risk factors and how infertility might impact their future lives.

Catherine Benedict, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, and her colleagues conducted this research and reported the results in the Journal of Adolescent and Young Adult Oncology.

The researchers assessed fertility concerns in 43 AYA cancer survivors. They were 16 to 24 at the time of the study, had been diagnosed with cancer between ages 14 and 18, and were at least 6 months post-treatment.

The subjects either completed an individual interview (n=26) or participated in 1 of 4 focus groups (n=17).

Before treatment, 5 of the males had banked sperm, but none of the females took steps to preserve their fertility. More males (50%) than females (39%) reported uncertainty about their fertility.

The researchers identified 3 themes when discussing fertility with the study subjects: fertility concerns, emotions raised when discussing fertility, and strategies used to manage fertility concerns.

Concerns

Some subjects expressed concerns about how potential infertility could affect dating and relationships with partners (8% of males and 20% of females).

Some subjects were concerned about the health risks associated with having children—both risks to the subjects themselves and to any potential children (39% of males and 30% of females).

And some subjects were concerned about how potential infertility would affect their lives going forward (31% of males and 20% of females).

Emotions

When it came to emotions associated with fertility discussions, some subjects said they felt distressed and overwhelmed (23% of males and 30% of females).

However, some subjects said they weren’t concerned about their fertility (31% of males and 15% of females) or they felt hopeful despite the risk of infertility (8% of males and 20% of females).

Managing concerns

The subjects also mentioned a few strategies for managing fertility concerns. Some said they had accepted infertility (23% of males and 15% of females).

Some subjects said they weren’t going to worry about their fertility until they were older and actually wanted to have children (23% of males and 20% of females).

And some subjects said they would rely on assisted reproductive technology if necessary (31% of males and 20% of females).

Dr Benedict and her colleagues said this study suggests AYA cancer survivors may have a number of reproductive concerns and fertility-related distress, which may affect other areas of psychosocial functioning.

So future research should explore how to best incorporate fertility-related informational and support services more fully into survivorship care.

Beagle

Photo by Julien Valroff

Gene therapy can safely and effectively treat factor VII (FVII) deficiency in dogs, according to research published in Blood.

Three of the 4 dogs treated expressed levels of FVII that would be therapeutic in humans, with long-term stability.

In one dog, the effects have persisted for more than 2.5 years and are ongoing.

In addition, researchers said the therapy appears safe, based on kidney function, liver function, and blood measurements.

The team believes this success in large animals holds considerable potential for a safe, effective, and long-lasting new treatment in humans with FVII deficiency.

“Our finding has great clinical relevance for patients with FVII deficiency,” said Paris Margaritis, DPhil, of The Children’s Hospital of Philadelphia in Pennsylvania.

“These dogs have the type of mutation found in the majority of patients with this disorder, so this approach could lead to a sustained gene therapy in people.”

Dr Margaritis and his colleagues studied dogs with a G96E missense FVII mutation (FVII-G96E), which have less than 1% FVII activity. The researchers said these dogs had undetectable plasmatic antigen by Western blot and therefore represent the most prevalent type of human FVII deficiency.

“We developed a unique animal model of this disease after identifying dogs with naturally occurring FVII deficiency,” Dr Margaritis said. “Our investigations enabled us to design the corrective gene to insert into our virus vector in the current study.”

The researchers tested liver-directed, adeno-associated viral (AAV) serotype 8 vector delivery of a canine FVII zymogen transgene (cFVII) in 4 FVII-G96E dogs, known as Otis, N22, N24, and N25.

The animals received escalating doses of AAV8-cFVII, ranging from 2E11 vg/kg to 4.95E13 vg/kg.

Efficacy

At baseline, all dogs had less than 1% cFVII activity levels. After receiving AAV8-cFVII, they experienced a reduction in prothrombin time that reached a plateau:

• From 121.1± 1.0s to 22.1 ± 3.2s in N24 (4.95E13 vg/kg)
• From 83.5 ± 18.4s to 25.0 ± 3.6s in N22 (2E12 vg/kg)
• From 96.0 ± 5.8s to 28.7 ± 3.7s in N25 (6E11 vg/kg)
• From 124.8 ± 4.6s to 50.4 ± 4.0s in Otis (2E11 vg/kg).

The researchers also observed an increase in cFVII expression for all of the dogs but Otis. Levels of cFVII antigen reached plateaus of:

• 8320 ± 1800 ng/ml in N24, which is 770 ± 167 percent of normal
• 307 ± 56 ng/ml in N22, which is 29.7 ± 6.2 percent of normal
• 170 ± 62 ng/ml in N25, which is 15.7 ± 5.7 percent of normal.

These clinically therapeutic cFVII antigen levels have, thus far, persisted for more than 1 year in N22 and N25 and for 2.6 years in N24.

Safety

The researchers found that measures of liver and kidney function were within the normal range in all of the dogs. Likewise, D-dimer and fibrinogen levels were within the normal range.

The team said these results suggest that continuous cFVII expression—even in N24, which averaged 8.3 μg/ml for 2.6 years—did not result in evident activation of the endogenous coagulation system or induce a chronic pathological state.

N24 did exhibit a transient elevation of anti-cFVII IgG2. However, this response was not inhibitory and did not affect the transgene expression plateau.

The researchers did not detect anti-cFVII IgG2 in the other 3 dogs, nor did the team detect anti-cFVII IgG1 in any of the dogs studied.

“This work is very exciting and promising,” said study author Timothy Nichols, MD, of The University of North Carolina at Chapel Hill.

“The FVII-deficient dogs tolerated the initial gene therapy infusions very well and have had no adverse side effects over several years of follow-up. In other related studies in dogs with hemophilia B, similar positive findings have translated to people with hemophilia B.”

Beagle

Photo by Julien Valroff

Gene therapy can safely and effectively treat factor VII (FVII) deficiency in dogs, according to research published in Blood.

Three of the 4 dogs treated expressed levels of FVII that would be therapeutic in humans, with long-term stability.

In one dog, the effects have persisted for more than 2.5 years and are ongoing.

In addition, researchers said the therapy appears safe, based on kidney function, liver function, and blood measurements.

The team believes this success in large animals holds considerable potential for a safe, effective, and long-lasting new treatment in humans with FVII deficiency.

“Our finding has great clinical relevance for patients with FVII deficiency,” said Paris Margaritis, DPhil, of The Children’s Hospital of Philadelphia in Pennsylvania.

“These dogs have the type of mutation found in the majority of patients with this disorder, so this approach could lead to a sustained gene therapy in people.”

Dr Margaritis and his colleagues studied dogs with a G96E missense FVII mutation (FVII-G96E), which have less than 1% FVII activity. The researchers said these dogs had undetectable plasmatic antigen by Western blot and therefore represent the most prevalent type of human FVII deficiency.

“We developed a unique animal model of this disease after identifying dogs with naturally occurring FVII deficiency,” Dr Margaritis said. “Our investigations enabled us to design the corrective gene to insert into our virus vector in the current study.”

The researchers tested liver-directed, adeno-associated viral (AAV) serotype 8 vector delivery of a canine FVII zymogen transgene (cFVII) in 4 FVII-G96E dogs, known as Otis, N22, N24, and N25.

The animals received escalating doses of AAV8-cFVII, ranging from 2E11 vg/kg to 4.95E13 vg/kg.

Efficacy

At baseline, all dogs had less than 1% cFVII activity levels. After receiving AAV8-cFVII, they experienced a reduction in prothrombin time that reached a plateau:

• From 121.1± 1.0s to 22.1 ± 3.2s in N24 (4.95E13 vg/kg)
• From 83.5 ± 18.4s to 25.0 ± 3.6s in N22 (2E12 vg/kg)
• From 96.0 ± 5.8s to 28.7 ± 3.7s in N25 (6E11 vg/kg)
• From 124.8 ± 4.6s to 50.4 ± 4.0s in Otis (2E11 vg/kg).

The researchers also observed an increase in cFVII expression for all of the dogs but Otis. Levels of cFVII antigen reached plateaus of:

• 8320 ± 1800 ng/ml in N24, which is 770 ± 167 percent of normal
• 307 ± 56 ng/ml in N22, which is 29.7 ± 6.2 percent of normal
• 170 ± 62 ng/ml in N25, which is 15.7 ± 5.7 percent of normal.

These clinically therapeutic cFVII antigen levels have, thus far, persisted for more than 1 year in N22 and N25 and for 2.6 years in N24.

Safety

The researchers found that measures of liver and kidney function were within the normal range in all of the dogs. Likewise, D-dimer and fibrinogen levels were within the normal range.

The team said these results suggest that continuous cFVII expression—even in N24, which averaged 8.3 μg/ml for 2.6 years—did not result in evident activation of the endogenous coagulation system or induce a chronic pathological state.

N24 did exhibit a transient elevation of anti-cFVII IgG2. However, this response was not inhibitory and did not affect the transgene expression plateau.

The researchers did not detect anti-cFVII IgG2 in the other 3 dogs, nor did the team detect anti-cFVII IgG1 in any of the dogs studied.

“This work is very exciting and promising,” said study author Timothy Nichols, MD, of The University of North Carolina at Chapel Hill.

“The FVII-deficient dogs tolerated the initial gene therapy infusions very well and have had no adverse side effects over several years of follow-up. In other related studies in dogs with hemophilia B, similar positive findings have translated to people with hemophilia B.”

Beagle

Photo by Julien Valroff

Gene therapy can safely and effectively treat factor VII (FVII) deficiency in dogs, according to research published in Blood.

Three of the 4 dogs treated expressed levels of FVII that would be therapeutic in humans, with long-term stability.

In one dog, the effects have persisted for more than 2.5 years and are ongoing.

In addition, researchers said the therapy appears safe, based on kidney function, liver function, and blood measurements.

The team believes this success in large animals holds considerable potential for a safe, effective, and long-lasting new treatment in humans with FVII deficiency.

“Our finding has great clinical relevance for patients with FVII deficiency,” said Paris Margaritis, DPhil, of The Children’s Hospital of Philadelphia in Pennsylvania.

“These dogs have the type of mutation found in the majority of patients with this disorder, so this approach could lead to a sustained gene therapy in people.”

Dr Margaritis and his colleagues studied dogs with a G96E missense FVII mutation (FVII-G96E), which have less than 1% FVII activity. The researchers said these dogs had undetectable plasmatic antigen by Western blot and therefore represent the most prevalent type of human FVII deficiency.

“We developed a unique animal model of this disease after identifying dogs with naturally occurring FVII deficiency,” Dr Margaritis said. “Our investigations enabled us to design the corrective gene to insert into our virus vector in the current study.”

The researchers tested liver-directed, adeno-associated viral (AAV) serotype 8 vector delivery of a canine FVII zymogen transgene (cFVII) in 4 FVII-G96E dogs, known as Otis, N22, N24, and N25.

The animals received escalating doses of AAV8-cFVII, ranging from 2E11 vg/kg to 4.95E13 vg/kg.

Efficacy

At baseline, all dogs had less than 1% cFVII activity levels. After receiving AAV8-cFVII, they experienced a reduction in prothrombin time that reached a plateau:

• From 121.1± 1.0s to 22.1 ± 3.2s in N24 (4.95E13 vg/kg)
• From 83.5 ± 18.4s to 25.0 ± 3.6s in N22 (2E12 vg/kg)
• From 96.0 ± 5.8s to 28.7 ± 3.7s in N25 (6E11 vg/kg)
• From 124.8 ± 4.6s to 50.4 ± 4.0s in Otis (2E11 vg/kg).

The researchers also observed an increase in cFVII expression for all of the dogs but Otis. Levels of cFVII antigen reached plateaus of:

• 8320 ± 1800 ng/ml in N24, which is 770 ± 167 percent of normal
• 307 ± 56 ng/ml in N22, which is 29.7 ± 6.2 percent of normal
• 170 ± 62 ng/ml in N25, which is 15.7 ± 5.7 percent of normal.

These clinically therapeutic cFVII antigen levels have, thus far, persisted for more than 1 year in N22 and N25 and for 2.6 years in N24.

Safety

The researchers found that measures of liver and kidney function were within the normal range in all of the dogs. Likewise, D-dimer and fibrinogen levels were within the normal range.

The team said these results suggest that continuous cFVII expression—even in N24, which averaged 8.3 μg/ml for 2.6 years—did not result in evident activation of the endogenous coagulation system or induce a chronic pathological state.

N24 did exhibit a transient elevation of anti-cFVII IgG2. However, this response was not inhibitory and did not affect the transgene expression plateau.

The researchers did not detect anti-cFVII IgG2 in the other 3 dogs, nor did the team detect anti-cFVII IgG1 in any of the dogs studied.

“This work is very exciting and promising,” said study author Timothy Nichols, MD, of The University of North Carolina at Chapel Hill.

“The FVII-deficient dogs tolerated the initial gene therapy infusions very well and have had no adverse side effects over several years of follow-up. In other related studies in dogs with hemophilia B, similar positive findings have translated to people with hemophilia B.”

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.

This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.

In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.

The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.

Trial results

The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.

This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.

In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.

The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.

Trial results

The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib (Kyprolis)

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.

The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.

This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.

In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.

The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.

Trial results

The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.

SAN ANTONIO – In massively transfused patients undergoing damage control laparotomy, postop hypertonic saline improves primary fascial closure rates at first take-back, according to investigators from the University of Texas Health Science Center at Houston.

After controlling for age, injury severity, and resuscitation volumes, primary fascial closure (PFC) at first take-back was almost four times as likely in patients who received hypertonic saline (HTS) after bleeding damage control laparotomy (DCL) instead of traditional isotonic maintenance fluids (odds ratio, 3.82; 95% confidence interval, 1.02-14.31; P = .047).

“In a group of seriously injured bleeding trauma patients undergoing DCL, the use of HTS was associated with a lower fluid balance and a higher rate of PFC at the first take-back,” the investigators concluded.

It’s unclear if the results are because of the hypertonic saline drawing off more edema fluid and making early PFC more likely, or because HTS patients in the study received less fluid than their standard maintenance peers – 30 cc/hr of 3% sodium chloride versus 125 cc/hr of traditional isotonic fluids post op.

PFC at first take-back is known to reduce complications. Previous studies have shown that HTS improves PFC rates, but they included moderately injured patients who would have been closed early no matter what postop fluids they received. The investigators wanted to see how well HTS worked in more severely injured patients.

The study compared 54 adult DCL patients from 2010 to 2011 who received traditional isotonic postop maintenance with 41 from 2013 to 2014 on HTS, both for 72 hours or until fascial closure, whichever came first. The university switched to HTS around 2012 based on earlier studies, allowing for the comparison. Patients in both groups received at least three RBC units during surgery, according to investigator Dr. Lindley Folkerson, a surgery resident at the university.

Twenty-seven HTS patients (66%) were closed at first take-back, versus 33 (61%) in the traditional maintenance group. The median time for closure was 29 hours in the HTS group but 38 hours in traditional maintenance patients (P = .035).

There were no between-group demographic or injury severity differences, but because the university has become more conservative with DCL in recent years, the HTS patients were more hypotensive and had greater baseline fluid deficits at emergency department arrival, and received more blood in the operating room. Even so, HTS patients had significantly lower fluid balances at 24 and 48 hours.

The university hasn’t noticed increased kidney injuries with lower-volume HTS, but that might prove to be a problem in a larger study, Dr. Folkerson said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

A limitation of the study is that patients were resuscitated as their physicians saw fit, so some in the HTS group likely got isotonic fluids. “We did not restrict fluids because they were on the HTS protocol. Crystalloid, colloid, and blood products were given as deemed necessary by the bedside physician,” she said.

The investigators had no disclosures.

[email protected]

SAN ANTONIO – In massively transfused patients undergoing damage control laparotomy, postop hypertonic saline improves primary fascial closure rates at first take-back, according to investigators from the University of Texas Health Science Center at Houston.

After controlling for age, injury severity, and resuscitation volumes, primary fascial closure (PFC) at first take-back was almost four times as likely in patients who received hypertonic saline (HTS) after bleeding damage control laparotomy (DCL) instead of traditional isotonic maintenance fluids (odds ratio, 3.82; 95% confidence interval, 1.02-14.31; P = .047).

“In a group of seriously injured bleeding trauma patients undergoing DCL, the use of HTS was associated with a lower fluid balance and a higher rate of PFC at the first take-back,” the investigators concluded.

It’s unclear if the results are because of the hypertonic saline drawing off more edema fluid and making early PFC more likely, or because HTS patients in the study received less fluid than their standard maintenance peers – 30 cc/hr of 3% sodium chloride versus 125 cc/hr of traditional isotonic fluids post op.

PFC at first take-back is known to reduce complications. Previous studies have shown that HTS improves PFC rates, but they included moderately injured patients who would have been closed early no matter what postop fluids they received. The investigators wanted to see how well HTS worked in more severely injured patients.

The study compared 54 adult DCL patients from 2010 to 2011 who received traditional isotonic postop maintenance with 41 from 2013 to 2014 on HTS, both for 72 hours or until fascial closure, whichever came first. The university switched to HTS around 2012 based on earlier studies, allowing for the comparison. Patients in both groups received at least three RBC units during surgery, according to investigator Dr. Lindley Folkerson, a surgery resident at the university.

Twenty-seven HTS patients (66%) were closed at first take-back, versus 33 (61%) in the traditional maintenance group. The median time for closure was 29 hours in the HTS group but 38 hours in traditional maintenance patients (P = .035).

There were no between-group demographic or injury severity differences, but because the university has become more conservative with DCL in recent years, the HTS patients were more hypotensive and had greater baseline fluid deficits at emergency department arrival, and received more blood in the operating room. Even so, HTS patients had significantly lower fluid balances at 24 and 48 hours.

The university hasn’t noticed increased kidney injuries with lower-volume HTS, but that might prove to be a problem in a larger study, Dr. Folkerson said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

A limitation of the study is that patients were resuscitated as their physicians saw fit, so some in the HTS group likely got isotonic fluids. “We did not restrict fluids because they were on the HTS protocol. Crystalloid, colloid, and blood products were given as deemed necessary by the bedside physician,” she said.

The investigators had no disclosures.

[email protected]

SAN ANTONIO – In massively transfused patients undergoing damage control laparotomy, postop hypertonic saline improves primary fascial closure rates at first take-back, according to investigators from the University of Texas Health Science Center at Houston.

After controlling for age, injury severity, and resuscitation volumes, primary fascial closure (PFC) at first take-back was almost four times as likely in patients who received hypertonic saline (HTS) after bleeding damage control laparotomy (DCL) instead of traditional isotonic maintenance fluids (odds ratio, 3.82; 95% confidence interval, 1.02-14.31; P = .047).

“In a group of seriously injured bleeding trauma patients undergoing DCL, the use of HTS was associated with a lower fluid balance and a higher rate of PFC at the first take-back,” the investigators concluded.

It’s unclear if the results are because of the hypertonic saline drawing off more edema fluid and making early PFC more likely, or because HTS patients in the study received less fluid than their standard maintenance peers – 30 cc/hr of 3% sodium chloride versus 125 cc/hr of traditional isotonic fluids post op.

PFC at first take-back is known to reduce complications. Previous studies have shown that HTS improves PFC rates, but they included moderately injured patients who would have been closed early no matter what postop fluids they received. The investigators wanted to see how well HTS worked in more severely injured patients.

The study compared 54 adult DCL patients from 2010 to 2011 who received traditional isotonic postop maintenance with 41 from 2013 to 2014 on HTS, both for 72 hours or until fascial closure, whichever came first. The university switched to HTS around 2012 based on earlier studies, allowing for the comparison. Patients in both groups received at least three RBC units during surgery, according to investigator Dr. Lindley Folkerson, a surgery resident at the university.

Twenty-seven HTS patients (66%) were closed at first take-back, versus 33 (61%) in the traditional maintenance group. The median time for closure was 29 hours in the HTS group but 38 hours in traditional maintenance patients (P = .035).

There were no between-group demographic or injury severity differences, but because the university has become more conservative with DCL in recent years, the HTS patients were more hypotensive and had greater baseline fluid deficits at emergency department arrival, and received more blood in the operating room. Even so, HTS patients had significantly lower fluid balances at 24 and 48 hours.

The university hasn’t noticed increased kidney injuries with lower-volume HTS, but that might prove to be a problem in a larger study, Dr. Folkerson said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

A limitation of the study is that patients were resuscitated as their physicians saw fit, so some in the HTS group likely got isotonic fluids. “We did not restrict fluids because they were on the HTS protocol. Crystalloid, colloid, and blood products were given as deemed necessary by the bedside physician,” she said.

The investigators had no disclosures.

[email protected]

ORLANDO – New diagnostic and treatment options are at the forefront of what’s new and exciting in the area of superficial cutaneous fungal infections, according to Dr. Adam Friedman.

“Although superficial cutaneous mycoses [are] extremely common, they can be quite a challenge for several reasons,” explained Dr. Friedman of the George Washington University in Washington, at the Orlando Dermatology Aesthetic and Clinical annual meeting, adding that “many of the common skin diseases are often confused for tineum, and vice versa.”

In this video interview, Dr. Friedman discusses what dermatologists should look for in terms of diagnosing and treating dermatophytes and onychomycosis, two of most common and increasingly treatable fungal infections patients are likely to present with.

Dr. Friedman did not report any relevant financial disclosures.

[email protected]

ORLANDO – New diagnostic and treatment options are at the forefront of what’s new and exciting in the area of superficial cutaneous fungal infections, according to Dr. Adam Friedman.

“Although superficial cutaneous mycoses [are] extremely common, they can be quite a challenge for several reasons,” explained Dr. Friedman of the George Washington University in Washington, at the Orlando Dermatology Aesthetic and Clinical annual meeting, adding that “many of the common skin diseases are often confused for tineum, and vice versa.”

In this video interview, Dr. Friedman discusses what dermatologists should look for in terms of diagnosing and treating dermatophytes and onychomycosis, two of most common and increasingly treatable fungal infections patients are likely to present with.

Dr. Friedman did not report any relevant financial disclosures.

[email protected]

ORLANDO – New diagnostic and treatment options are at the forefront of what’s new and exciting in the area of superficial cutaneous fungal infections, according to Dr. Adam Friedman.

“Although superficial cutaneous mycoses [are] extremely common, they can be quite a challenge for several reasons,” explained Dr. Friedman of the George Washington University in Washington, at the Orlando Dermatology Aesthetic and Clinical annual meeting, adding that “many of the common skin diseases are often confused for tineum, and vice versa.”

In this video interview, Dr. Friedman discusses what dermatologists should look for in terms of diagnosing and treating dermatophytes and onychomycosis, two of most common and increasingly treatable fungal infections patients are likely to present with.

Dr. Friedman did not report any relevant financial disclosures.

[email protected]

We are into a new year, and among many New Year’s resolutions we hear is the resolution to take off body weight. That people are going for a new start, a chance to begin again, is actually good; it brings new hope and vigor to the issue. But sadly, most Americans making this resolution find themselves starting anew at a weight higher than they were the previous new year when they made the same resolution. Despite ourselves, we diet, exercise, and take off some pounds and then return to our previous behaviors that got us to wanting to take off the pounds in the first place.

Can psychiatry get into the body weight adventure and begin to lead the way to solutions? What I hope to do in this new column, “Weighty Issues,” is to share some of what I have learned in becoming an obesity medicine specialist, and learn from other experts who have been assessing and treating overweight and obesity for years.

I also hope to learn and share what we as psychiatrists are doing to manage our own weight (as many of us sit for a living) and lifestyles.

Coming to terms

About two-thirds of Americans are by medical calculations overweight, with half of that proportion actually medically obese. It is well-known that being overweight is a major risk factor for most of the illnesses that cause morbidity and early death among Americans. But this public health crisis was only classified an illness by the American Medical Association in 2013. What took us so long?

The topic of over body weight and psychiatry has been heavy on my mind for many years. It always puzzled me that psychiatry concentrated on anorexia nervosa, bulimia, and binge eating but was largely not focusing on the issue that was creeping up around us and becoming the major public health concern: that of overweight and obesity.

I knew that we were to concern ourselves only with illness but by ignoring the issue we, along with the rest of medicine, have promoted major, chronic illnesses of diabetes, heart disease, cancer, and so on. Fortunately for us, the AMA declared obesity a medical illness, but unfortunately, the way the reimbursement reads for treating obesity, one must be a sort of primary care physician or surgeon to get paid for the work. To my way of thinking, psychiatrists are the best physicians to be working in the field of overweight and obesity medicine, because we – more than any other medical specialty – understand that thoughts and feelings are involved in behavior. We understand that to be successful long-term in any endeavor, one must understand and harness one’s thoughts and feelings.

Moreover, we, more than physicians in other specialties, understand that the treater’s simple transference and countertransference, and the patient’s transference, can determine the trajectory and outcome of the treatment process. Additionally, psychiatrists regularly see their patients more often and over longer periods of time than do other physicians while developing and maintaining respectful and supportive relationships that can best handle the very personal issue of weight.

Surgery often not the answer

After having been a part of many psychiatric and psychological pre–bariatric surgery screenings over many years and having known many patients, friends, and colleagues who had undergone the different surgical treatments for overweight with complications and/or obesity, only to see them, many years later, larger than they were before the surgical intervention, I began to think that cutting it out was not the only definitive way to get better health measures. I knew that each surgical candidate really meant it when they pledged to follow through indefinitely but that feelings and life had intervened, and those were more powerful than surgery. That led me to think like a psychiatrist, and learn from and keep on learning from the feelings throughout life’s challenges and not like a surgeon, whose view is “once it is cut out, it is finished.”

It even led me to think medically radical thoughts that rapid weight loss through diet and lifestyle intervention, such as the weight loss that is achieved through surgery, could be a very good thing with one major caveat ... long-term intervention (psychiatry, the discipline, knows something about long-term intervention). That kind of thinking led me to try to register for a lifestyle program that was sold out at that time. A course in Obesity Medicine, the crux of the matter, was not sold out. I took one course and was hooked, learning all that I did not know about overweight and obesity, and realizing just how complicated the matter of weight actually is.

In time, I studied and learned more, saw more patients, and became a diplomate of the American Board of Obesity Medicine (ABOM). Of the approximately 1,300 diplomates of the ABOM, only 15 identify as having psychiatry as their primary specialty. The board reports that there may be other psychiatrists who are also boarded in internal medicine or pediatrics or surgery, but specific information is not available.

Those of us who prescribe typical and atypical antipsychotic agents and some of the older and newer antidepressants are familiar with the weight gain that can be attendant to these medications. We also are familiar with metabolic syndrome, which can be associated and our need to follow fasting blood glucose and lipid levels as well as waist circumference, height, and weight.

Many of us also will educate our patients about eating fewer sweets and drinking fewer sugar sweetened beverages, consuming fewer starches, and we will advise our patients to increase their exercise. We may even prescribe metformin if the fasting blood sugar and hemoglobin A1C begin to creep upward. In addition, we are constantly trying to offset the side effects of medications that we prescribe for very serious illnesses. In short, psychiatrists already are in the obesity medicine arena.

Addressing personal challenges

Talking the talk and walking the walk is so important in the area of overweight and obesity. I have struggled with overweight most of my adult life and have been “overnutritioned” – the Chinese term for overweight, off and on during my career in psychiatry. During my obesity medicine studies, I took my own weight and lifestyle seriously, and lost a significant amount of weight. Friends and patients asked me if I were well. Over time, some patients who had been with me for years volunteered how they felt about my voluntary weight loss. Most said that I no longer looked powerful; some said that I looked like a lightweight – not a serious person.

Interestingly, over time, all of my patients who had weight issues of their own began to manage their own weight better, and began to talk about their feelings and relationship to food, exercise, and weight. We have all realized that there is more under that puffy cover than meets the eye and that it insulates a whole host of stuff. Calories in and calories out become a superficial path toward a solution.

Regarding simple transference and countertransference ... many physicians have powerful adverse feelings about patients who are overweight or obese and really struggle with working with these patients. One of my friends, a family medicine specialist, told me that he cannot look at them and has told his staff not to assign those patients to him, because they do not comply and then do not come back to follow up. It is likely that his patients pick up on his disdain, anger, and lack of hope for them, and do not return in order to protect their feelings. Interestingly, this friend has struggled with his own weight throughout his professional life. Perhaps psychiatry could be useful to the myriad of other physicians like my friend who have visceral reactions to patients with weight issues so that the physicians can be kinder to themselves and their patients can receive the care, understanding, and respect that they deserve.

Attaining and maintaining a healthy weight across the life cycles is a complicated thought-, feeling-, and event-filled endeavor. I look forward to sharing basic science, clinical science, research, and anecdotal reports as we explore “Weighty Issues.”

Dr. Harris, a diplomate of the American Board of Obesity Medicine, is in private practice in adult and geriatric psychiatry in Hartford, Conn. She also works as a psychiatric consultant to continuing care retirement organizations and professional groups. Dr. Harris, a former president of the Black Psychiatrists of America, is a Distinguished Fellow of the American Psychiatric Association. Besides psychotherapy, her major clinical interests include geriatrics and the interface between general medicine and psychiatry.

We are into a new year, and among many New Year’s resolutions we hear is the resolution to take off body weight. That people are going for a new start, a chance to begin again, is actually good; it brings new hope and vigor to the issue. But sadly, most Americans making this resolution find themselves starting anew at a weight higher than they were the previous new year when they made the same resolution. Despite ourselves, we diet, exercise, and take off some pounds and then return to our previous behaviors that got us to wanting to take off the pounds in the first place.

Can psychiatry get into the body weight adventure and begin to lead the way to solutions? What I hope to do in this new column, “Weighty Issues,” is to share some of what I have learned in becoming an obesity medicine specialist, and learn from other experts who have been assessing and treating overweight and obesity for years.

I also hope to learn and share what we as psychiatrists are doing to manage our own weight (as many of us sit for a living) and lifestyles.

Coming to terms

About two-thirds of Americans are by medical calculations overweight, with half of that proportion actually medically obese. It is well-known that being overweight is a major risk factor for most of the illnesses that cause morbidity and early death among Americans. But this public health crisis was only classified an illness by the American Medical Association in 2013. What took us so long?

The topic of over body weight and psychiatry has been heavy on my mind for many years. It always puzzled me that psychiatry concentrated on anorexia nervosa, bulimia, and binge eating but was largely not focusing on the issue that was creeping up around us and becoming the major public health concern: that of overweight and obesity.

I knew that we were to concern ourselves only with illness but by ignoring the issue we, along with the rest of medicine, have promoted major, chronic illnesses of diabetes, heart disease, cancer, and so on. Fortunately for us, the AMA declared obesity a medical illness, but unfortunately, the way the reimbursement reads for treating obesity, one must be a sort of primary care physician or surgeon to get paid for the work. To my way of thinking, psychiatrists are the best physicians to be working in the field of overweight and obesity medicine, because we – more than any other medical specialty – understand that thoughts and feelings are involved in behavior. We understand that to be successful long-term in any endeavor, one must understand and harness one’s thoughts and feelings.

Moreover, we, more than physicians in other specialties, understand that the treater’s simple transference and countertransference, and the patient’s transference, can determine the trajectory and outcome of the treatment process. Additionally, psychiatrists regularly see their patients more often and over longer periods of time than do other physicians while developing and maintaining respectful and supportive relationships that can best handle the very personal issue of weight.

Surgery often not the answer

After having been a part of many psychiatric and psychological pre–bariatric surgery screenings over many years and having known many patients, friends, and colleagues who had undergone the different surgical treatments for overweight with complications and/or obesity, only to see them, many years later, larger than they were before the surgical intervention, I began to think that cutting it out was not the only definitive way to get better health measures. I knew that each surgical candidate really meant it when they pledged to follow through indefinitely but that feelings and life had intervened, and those were more powerful than surgery. That led me to think like a psychiatrist, and learn from and keep on learning from the feelings throughout life’s challenges and not like a surgeon, whose view is “once it is cut out, it is finished.”

It even led me to think medically radical thoughts that rapid weight loss through diet and lifestyle intervention, such as the weight loss that is achieved through surgery, could be a very good thing with one major caveat ... long-term intervention (psychiatry, the discipline, knows something about long-term intervention). That kind of thinking led me to try to register for a lifestyle program that was sold out at that time. A course in Obesity Medicine, the crux of the matter, was not sold out. I took one course and was hooked, learning all that I did not know about overweight and obesity, and realizing just how complicated the matter of weight actually is.

In time, I studied and learned more, saw more patients, and became a diplomate of the American Board of Obesity Medicine (ABOM). Of the approximately 1,300 diplomates of the ABOM, only 15 identify as having psychiatry as their primary specialty. The board reports that there may be other psychiatrists who are also boarded in internal medicine or pediatrics or surgery, but specific information is not available.

Those of us who prescribe typical and atypical antipsychotic agents and some of the older and newer antidepressants are familiar with the weight gain that can be attendant to these medications. We also are familiar with metabolic syndrome, which can be associated and our need to follow fasting blood glucose and lipid levels as well as waist circumference, height, and weight.

Many of us also will educate our patients about eating fewer sweets and drinking fewer sugar sweetened beverages, consuming fewer starches, and we will advise our patients to increase their exercise. We may even prescribe metformin if the fasting blood sugar and hemoglobin A1C begin to creep upward. In addition, we are constantly trying to offset the side effects of medications that we prescribe for very serious illnesses. In short, psychiatrists already are in the obesity medicine arena.

Addressing personal challenges

Talking the talk and walking the walk is so important in the area of overweight and obesity. I have struggled with overweight most of my adult life and have been “overnutritioned” – the Chinese term for overweight, off and on during my career in psychiatry. During my obesity medicine studies, I took my own weight and lifestyle seriously, and lost a significant amount of weight. Friends and patients asked me if I were well. Over time, some patients who had been with me for years volunteered how they felt about my voluntary weight loss. Most said that I no longer looked powerful; some said that I looked like a lightweight – not a serious person.

Interestingly, over time, all of my patients who had weight issues of their own began to manage their own weight better, and began to talk about their feelings and relationship to food, exercise, and weight. We have all realized that there is more under that puffy cover than meets the eye and that it insulates a whole host of stuff. Calories in and calories out become a superficial path toward a solution.

Regarding simple transference and countertransference ... many physicians have powerful adverse feelings about patients who are overweight or obese and really struggle with working with these patients. One of my friends, a family medicine specialist, told me that he cannot look at them and has told his staff not to assign those patients to him, because they do not comply and then do not come back to follow up. It is likely that his patients pick up on his disdain, anger, and lack of hope for them, and do not return in order to protect their feelings. Interestingly, this friend has struggled with his own weight throughout his professional life. Perhaps psychiatry could be useful to the myriad of other physicians like my friend who have visceral reactions to patients with weight issues so that the physicians can be kinder to themselves and their patients can receive the care, understanding, and respect that they deserve.

Attaining and maintaining a healthy weight across the life cycles is a complicated thought-, feeling-, and event-filled endeavor. I look forward to sharing basic science, clinical science, research, and anecdotal reports as we explore “Weighty Issues.”

Dr. Harris, a diplomate of the American Board of Obesity Medicine, is in private practice in adult and geriatric psychiatry in Hartford, Conn. She also works as a psychiatric consultant to continuing care retirement organizations and professional groups. Dr. Harris, a former president of the Black Psychiatrists of America, is a Distinguished Fellow of the American Psychiatric Association. Besides psychotherapy, her major clinical interests include geriatrics and the interface between general medicine and psychiatry.

We are into a new year, and among many New Year’s resolutions we hear is the resolution to take off body weight. That people are going for a new start, a chance to begin again, is actually good; it brings new hope and vigor to the issue. But sadly, most Americans making this resolution find themselves starting anew at a weight higher than they were the previous new year when they made the same resolution. Despite ourselves, we diet, exercise, and take off some pounds and then return to our previous behaviors that got us to wanting to take off the pounds in the first place.

Can psychiatry get into the body weight adventure and begin to lead the way to solutions? What I hope to do in this new column, “Weighty Issues,” is to share some of what I have learned in becoming an obesity medicine specialist, and learn from other experts who have been assessing and treating overweight and obesity for years.

I also hope to learn and share what we as psychiatrists are doing to manage our own weight (as many of us sit for a living) and lifestyles.

Coming to terms

About two-thirds of Americans are by medical calculations overweight, with half of that proportion actually medically obese. It is well-known that being overweight is a major risk factor for most of the illnesses that cause morbidity and early death among Americans. But this public health crisis was only classified an illness by the American Medical Association in 2013. What took us so long?

The topic of over body weight and psychiatry has been heavy on my mind for many years. It always puzzled me that psychiatry concentrated on anorexia nervosa, bulimia, and binge eating but was largely not focusing on the issue that was creeping up around us and becoming the major public health concern: that of overweight and obesity.

I knew that we were to concern ourselves only with illness but by ignoring the issue we, along with the rest of medicine, have promoted major, chronic illnesses of diabetes, heart disease, cancer, and so on. Fortunately for us, the AMA declared obesity a medical illness, but unfortunately, the way the reimbursement reads for treating obesity, one must be a sort of primary care physician or surgeon to get paid for the work. To my way of thinking, psychiatrists are the best physicians to be working in the field of overweight and obesity medicine, because we – more than any other medical specialty – understand that thoughts and feelings are involved in behavior. We understand that to be successful long-term in any endeavor, one must understand and harness one’s thoughts and feelings.

Moreover, we, more than physicians in other specialties, understand that the treater’s simple transference and countertransference, and the patient’s transference, can determine the trajectory and outcome of the treatment process. Additionally, psychiatrists regularly see their patients more often and over longer periods of time than do other physicians while developing and maintaining respectful and supportive relationships that can best handle the very personal issue of weight.

Surgery often not the answer

After having been a part of many psychiatric and psychological pre–bariatric surgery screenings over many years and having known many patients, friends, and colleagues who had undergone the different surgical treatments for overweight with complications and/or obesity, only to see them, many years later, larger than they were before the surgical intervention, I began to think that cutting it out was not the only definitive way to get better health measures. I knew that each surgical candidate really meant it when they pledged to follow through indefinitely but that feelings and life had intervened, and those were more powerful than surgery. That led me to think like a psychiatrist, and learn from and keep on learning from the feelings throughout life’s challenges and not like a surgeon, whose view is “once it is cut out, it is finished.”

It even led me to think medically radical thoughts that rapid weight loss through diet and lifestyle intervention, such as the weight loss that is achieved through surgery, could be a very good thing with one major caveat ... long-term intervention (psychiatry, the discipline, knows something about long-term intervention). That kind of thinking led me to try to register for a lifestyle program that was sold out at that time. A course in Obesity Medicine, the crux of the matter, was not sold out. I took one course and was hooked, learning all that I did not know about overweight and obesity, and realizing just how complicated the matter of weight actually is.

In time, I studied and learned more, saw more patients, and became a diplomate of the American Board of Obesity Medicine (ABOM). Of the approximately 1,300 diplomates of the ABOM, only 15 identify as having psychiatry as their primary specialty. The board reports that there may be other psychiatrists who are also boarded in internal medicine or pediatrics or surgery, but specific information is not available.

Those of us who prescribe typical and atypical antipsychotic agents and some of the older and newer antidepressants are familiar with the weight gain that can be attendant to these medications. We also are familiar with metabolic syndrome, which can be associated and our need to follow fasting blood glucose and lipid levels as well as waist circumference, height, and weight.

Many of us also will educate our patients about eating fewer sweets and drinking fewer sugar sweetened beverages, consuming fewer starches, and we will advise our patients to increase their exercise. We may even prescribe metformin if the fasting blood sugar and hemoglobin A1C begin to creep upward. In addition, we are constantly trying to offset the side effects of medications that we prescribe for very serious illnesses. In short, psychiatrists already are in the obesity medicine arena.

Addressing personal challenges

Talking the talk and walking the walk is so important in the area of overweight and obesity. I have struggled with overweight most of my adult life and have been “overnutritioned” – the Chinese term for overweight, off and on during my career in psychiatry. During my obesity medicine studies, I took my own weight and lifestyle seriously, and lost a significant amount of weight. Friends and patients asked me if I were well. Over time, some patients who had been with me for years volunteered how they felt about my voluntary weight loss. Most said that I no longer looked powerful; some said that I looked like a lightweight – not a serious person.

Interestingly, over time, all of my patients who had weight issues of their own began to manage their own weight better, and began to talk about their feelings and relationship to food, exercise, and weight. We have all realized that there is more under that puffy cover than meets the eye and that it insulates a whole host of stuff. Calories in and calories out become a superficial path toward a solution.

Regarding simple transference and countertransference ... many physicians have powerful adverse feelings about patients who are overweight or obese and really struggle with working with these patients. One of my friends, a family medicine specialist, told me that he cannot look at them and has told his staff not to assign those patients to him, because they do not comply and then do not come back to follow up. It is likely that his patients pick up on his disdain, anger, and lack of hope for them, and do not return in order to protect their feelings. Interestingly, this friend has struggled with his own weight throughout his professional life. Perhaps psychiatry could be useful to the myriad of other physicians like my friend who have visceral reactions to patients with weight issues so that the physicians can be kinder to themselves and their patients can receive the care, understanding, and respect that they deserve.

Attaining and maintaining a healthy weight across the life cycles is a complicated thought-, feeling-, and event-filled endeavor. I look forward to sharing basic science, clinical science, research, and anecdotal reports as we explore “Weighty Issues.”

Dr. Harris, a diplomate of the American Board of Obesity Medicine, is in private practice in adult and geriatric psychiatry in Hartford, Conn. She also works as a psychiatric consultant to continuing care retirement organizations and professional groups. Dr. Harris, a former president of the Black Psychiatrists of America, is a Distinguished Fellow of the American Psychiatric Association. Besides psychotherapy, her major clinical interests include geriatrics and the interface between general medicine and psychiatry.

ORLANDO – Dermatologists with the right patient population should consider incorporating photodynamic therapy (PDT) into their practices, as it is becoming an increasingly popular and effective.

Although most dermatologists know about PDT, “They’re not as comfortable setting up the office” and often don’t know the best ways to use PDT to achieve optimal treatment outcomes, explained Dr. Neal Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego, during his session at the Orlando Dermatology Aesthetic and Clinical annual meeting.

In this video interview, Dr. Bhatia, explains the benefits of PDT, what type of patient would be best suited for this treatment, and why it’s increasingly important for dermatologists to offer this treatment to their patients – even if they’ve never considered doing so before.

Dr. Bhatia is a clinical investigator and consultant with Dusa Pharmaceuticals and Biofrontera. He did not report any other relevant disclosures.

[email protected]

ORLANDO – Dermatologists with the right patient population should consider incorporating photodynamic therapy (PDT) into their practices, as it is becoming an increasingly popular and effective.

Although most dermatologists know about PDT, “They’re not as comfortable setting up the office” and often don’t know the best ways to use PDT to achieve optimal treatment outcomes, explained Dr. Neal Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego, during his session at the Orlando Dermatology Aesthetic and Clinical annual meeting.

In this video interview, Dr. Bhatia, explains the benefits of PDT, what type of patient would be best suited for this treatment, and why it’s increasingly important for dermatologists to offer this treatment to their patients – even if they’ve never considered doing so before.

Dr. Bhatia is a clinical investigator and consultant with Dusa Pharmaceuticals and Biofrontera. He did not report any other relevant disclosures.

[email protected]

ORLANDO – Dermatologists with the right patient population should consider incorporating photodynamic therapy (PDT) into their practices, as it is becoming an increasingly popular and effective.

Although most dermatologists know about PDT, “They’re not as comfortable setting up the office” and often don’t know the best ways to use PDT to achieve optimal treatment outcomes, explained Dr. Neal Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego, during his session at the Orlando Dermatology Aesthetic and Clinical annual meeting.

In this video interview, Dr. Bhatia, explains the benefits of PDT, what type of patient would be best suited for this treatment, and why it’s increasingly important for dermatologists to offer this treatment to their patients – even if they’ve never considered doing so before.

Dr. Bhatia is a clinical investigator and consultant with Dusa Pharmaceuticals and Biofrontera. He did not report any other relevant disclosures.

[email protected]

Heart transplant volumes in the United States have remained static since the start of the century because of improved trauma prevention and treatment, but that has challenged cardiologists to find enough donor hearts for the growing ranks of advanced heart failure patients. So a multidisciplinary team at the University of Washington in Seattle initiated a quality improvement program that doubled transplant volume without any change in transplant-related deaths by accepting hearts they would have otherwise discarded.

The study came about after the researchers determined that a large number of donor hearts from their own organ procurement program were being sent to other transplant centers. So they gathered a multidisciplinary team of transplant surgeons, cardiologists, and members of the organ procurement program to study ways to improve its center-specific organ utilization rate. The endeavor resulted in an increase in utilization rates from 28% to 49% in a year, a rate that has been sustained through a second year, according to study findings published in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:238-43).

“The simple process of systematically reviewing donor turn down events as a group tended to reduce variability [and] increase confidence in expanded criteria donors and resulted in improved donor organ utilization and transplant volumes,” lead author Dr. Jason Smith and colleagues said.

The 30-day and 1-year death rates were similar before and after the quality improvement program started, but the death rates of those on the heart wait list declined from 17.2% to 12%, “which was not statistically significant,” Dr. Smith and coauthors said, “but does show that increasing use of organs that may be outside of the usual pattern has a trend toward improved wait list survival and needs to be considered when assessing donor hearts.”

Because of excellent results of heart transplants in patients with advanced heart failure, a number of investigators have proposed expanding the population of heart donors to include older people, those with higher risk of infectious disease, or with heart disease such as coronary artery disease and left ventricular hypertrophy, Dr. Smith and coauthors said. Their own review found a higher-than-expected rate of donor hearts sent to other centers from the University of Washington organ procurement program.

The multidisciplinary team analyzed the organs the University of Washington surgeons refused and sent to other institutions from July 2012 to June 2013.

For a year after that, the multidisciplinary group did real-time analysis of organ refusal along with quarterly reviews “in a non-confrontational, proactive” setting, as Dr. Smith and his colleagues described it. The group held open discussions on refused organs that were ultimately transplanted elsewhere. “The review process was facilitated to provide a constructive environment to encourage development of best practices and consistency,” the researchers noted. The quality improvement program led to an increase in the unit’s transplant volume despite fewer donor offers.

The researchers acknowledged that donor assessment has been the focus of much controversy. They pointed out that average donor age has increased over the last 20 years from 29 years to 33 years and has since retreated to 31 years, and some programs utilize donors up to their mid-60s. Also, previous studies have advocated for the use of donors who meet the criteria of the Centers for Disease Control and Prevention high risk behavior of infection as well as some drug abusers because of the low-risk of transmission and emerging evidence affirming the safety of hearts of drug users.

“The individual decision to utilize or discard a donor organ is one of the most challenging aspects of transplant medicine,” Dr. Smith and colleagues said. “It requires balancing donor risks against the exigencies of the recipient.”

Today, the multidisciplinary team evaluates each heart offered for donation and is exploring ways to accept even more donor hearts, even discarded hearts. “This represents a large, untapped pool of potential donor hearts that might add to the net number of transplants performed nationally and not merely redistribute organ usage,” Dr. Smith and colleagues said.

Dr. Smith is a consultant for Thoratec and is a primary site investigator for the EXPAND Trial sponsored by TransMedics. Dr. Todd Dardas is supported by the American College of Cardiology/Daiichi Sankyo Career Development Award. Dr. Jay Pal receives grant support from Tenax. Dr. Wayne Levy is a consultant for HeartWare, Novartis, GE Healthcare, Pharmin, and Biotronik. Dr. Claudius Mahr is a consultant for Thoratec, HeartWare and Abiomed. Dr. Nahush Mokadam is a consultant for Thoratec, HeartWare, Syncardia and St. Jude Medical, and has research grants from Thoratec, HeartWare and Syncardia. The other coauthors had no relationships to disclose.

Heart transplant volumes in the United States have remained static since the start of the century because of improved trauma prevention and treatment, but that has challenged cardiologists to find enough donor hearts for the growing ranks of advanced heart failure patients. So a multidisciplinary team at the University of Washington in Seattle initiated a quality improvement program that doubled transplant volume without any change in transplant-related deaths by accepting hearts they would have otherwise discarded.

The study came about after the researchers determined that a large number of donor hearts from their own organ procurement program were being sent to other transplant centers. So they gathered a multidisciplinary team of transplant surgeons, cardiologists, and members of the organ procurement program to study ways to improve its center-specific organ utilization rate. The endeavor resulted in an increase in utilization rates from 28% to 49% in a year, a rate that has been sustained through a second year, according to study findings published in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:238-43).

“The simple process of systematically reviewing donor turn down events as a group tended to reduce variability [and] increase confidence in expanded criteria donors and resulted in improved donor organ utilization and transplant volumes,” lead author Dr. Jason Smith and colleagues said.

The 30-day and 1-year death rates were similar before and after the quality improvement program started, but the death rates of those on the heart wait list declined from 17.2% to 12%, “which was not statistically significant,” Dr. Smith and coauthors said, “but does show that increasing use of organs that may be outside of the usual pattern has a trend toward improved wait list survival and needs to be considered when assessing donor hearts.”

Because of excellent results of heart transplants in patients with advanced heart failure, a number of investigators have proposed expanding the population of heart donors to include older people, those with higher risk of infectious disease, or with heart disease such as coronary artery disease and left ventricular hypertrophy, Dr. Smith and coauthors said. Their own review found a higher-than-expected rate of donor hearts sent to other centers from the University of Washington organ procurement program.

The multidisciplinary team analyzed the organs the University of Washington surgeons refused and sent to other institutions from July 2012 to June 2013.

For a year after that, the multidisciplinary group did real-time analysis of organ refusal along with quarterly reviews “in a non-confrontational, proactive” setting, as Dr. Smith and his colleagues described it. The group held open discussions on refused organs that were ultimately transplanted elsewhere. “The review process was facilitated to provide a constructive environment to encourage development of best practices and consistency,” the researchers noted. The quality improvement program led to an increase in the unit’s transplant volume despite fewer donor offers.

The researchers acknowledged that donor assessment has been the focus of much controversy. They pointed out that average donor age has increased over the last 20 years from 29 years to 33 years and has since retreated to 31 years, and some programs utilize donors up to their mid-60s. Also, previous studies have advocated for the use of donors who meet the criteria of the Centers for Disease Control and Prevention high risk behavior of infection as well as some drug abusers because of the low-risk of transmission and emerging evidence affirming the safety of hearts of drug users.

“The individual decision to utilize or discard a donor organ is one of the most challenging aspects of transplant medicine,” Dr. Smith and colleagues said. “It requires balancing donor risks against the exigencies of the recipient.”

Today, the multidisciplinary team evaluates each heart offered for donation and is exploring ways to accept even more donor hearts, even discarded hearts. “This represents a large, untapped pool of potential donor hearts that might add to the net number of transplants performed nationally and not merely redistribute organ usage,” Dr. Smith and colleagues said.

Dr. Smith is a consultant for Thoratec and is a primary site investigator for the EXPAND Trial sponsored by TransMedics. Dr. Todd Dardas is supported by the American College of Cardiology/Daiichi Sankyo Career Development Award. Dr. Jay Pal receives grant support from Tenax. Dr. Wayne Levy is a consultant for HeartWare, Novartis, GE Healthcare, Pharmin, and Biotronik. Dr. Claudius Mahr is a consultant for Thoratec, HeartWare and Abiomed. Dr. Nahush Mokadam is a consultant for Thoratec, HeartWare, Syncardia and St. Jude Medical, and has research grants from Thoratec, HeartWare and Syncardia. The other coauthors had no relationships to disclose.

Heart transplant volumes in the United States have remained static since the start of the century because of improved trauma prevention and treatment, but that has challenged cardiologists to find enough donor hearts for the growing ranks of advanced heart failure patients. So a multidisciplinary team at the University of Washington in Seattle initiated a quality improvement program that doubled transplant volume without any change in transplant-related deaths by accepting hearts they would have otherwise discarded.

The study came about after the researchers determined that a large number of donor hearts from their own organ procurement program were being sent to other transplant centers. So they gathered a multidisciplinary team of transplant surgeons, cardiologists, and members of the organ procurement program to study ways to improve its center-specific organ utilization rate. The endeavor resulted in an increase in utilization rates from 28% to 49% in a year, a rate that has been sustained through a second year, according to study findings published in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:238-43).

“The simple process of systematically reviewing donor turn down events as a group tended to reduce variability [and] increase confidence in expanded criteria donors and resulted in improved donor organ utilization and transplant volumes,” lead author Dr. Jason Smith and colleagues said.

The 30-day and 1-year death rates were similar before and after the quality improvement program started, but the death rates of those on the heart wait list declined from 17.2% to 12%, “which was not statistically significant,” Dr. Smith and coauthors said, “but does show that increasing use of organs that may be outside of the usual pattern has a trend toward improved wait list survival and needs to be considered when assessing donor hearts.”

Because of excellent results of heart transplants in patients with advanced heart failure, a number of investigators have proposed expanding the population of heart donors to include older people, those with higher risk of infectious disease, or with heart disease such as coronary artery disease and left ventricular hypertrophy, Dr. Smith and coauthors said. Their own review found a higher-than-expected rate of donor hearts sent to other centers from the University of Washington organ procurement program.

The multidisciplinary team analyzed the organs the University of Washington surgeons refused and sent to other institutions from July 2012 to June 2013.

For a year after that, the multidisciplinary group did real-time analysis of organ refusal along with quarterly reviews “in a non-confrontational, proactive” setting, as Dr. Smith and his colleagues described it. The group held open discussions on refused organs that were ultimately transplanted elsewhere. “The review process was facilitated to provide a constructive environment to encourage development of best practices and consistency,” the researchers noted. The quality improvement program led to an increase in the unit’s transplant volume despite fewer donor offers.

The researchers acknowledged that donor assessment has been the focus of much controversy. They pointed out that average donor age has increased over the last 20 years from 29 years to 33 years and has since retreated to 31 years, and some programs utilize donors up to their mid-60s. Also, previous studies have advocated for the use of donors who meet the criteria of the Centers for Disease Control and Prevention high risk behavior of infection as well as some drug abusers because of the low-risk of transmission and emerging evidence affirming the safety of hearts of drug users.

“The individual decision to utilize or discard a donor organ is one of the most challenging aspects of transplant medicine,” Dr. Smith and colleagues said. “It requires balancing donor risks against the exigencies of the recipient.”

Today, the multidisciplinary team evaluates each heart offered for donation and is exploring ways to accept even more donor hearts, even discarded hearts. “This represents a large, untapped pool of potential donor hearts that might add to the net number of transplants performed nationally and not merely redistribute organ usage,” Dr. Smith and colleagues said.

Dr. Smith is a consultant for Thoratec and is a primary site investigator for the EXPAND Trial sponsored by TransMedics. Dr. Todd Dardas is supported by the American College of Cardiology/Daiichi Sankyo Career Development Award. Dr. Jay Pal receives grant support from Tenax. Dr. Wayne Levy is a consultant for HeartWare, Novartis, GE Healthcare, Pharmin, and Biotronik. Dr. Claudius Mahr is a consultant for Thoratec, HeartWare and Abiomed. Dr. Nahush Mokadam is a consultant for Thoratec, HeartWare, Syncardia and St. Jude Medical, and has research grants from Thoratec, HeartWare and Syncardia. The other coauthors had no relationships to disclose.