SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

Click here to listen to

Dr. Maynard and others at the public hearing

Click here to listen to

Dr. Maynard and others at the public hearing

Click here to listen to

Dr. Maynard and others at the public hearing

BERLIN – The cumulative incidence of spondyloarthropathy in the first decade after diagnosis of inflammatory bowel disease is about 1 in 50 patients, climbing to 1 in 25 at 20 years and 1 in 14 at 30 years, according to the first population-based study to scrutinize the issue.

The incidence of spondyloarthropathy following diagnosis of ulcerative colitis is about half that seen in Crohn’s disease patients, said Dr. Eric L. Matteson at the Annual European Congress of Rheumatology.

Dr. Matteson, a professor of medicine and chair of the department of rheumatology at the Mayo Clinic, Rochester, Minn., and his coinvestigators analyzed the medical records of Olmsted County, Minn., residents who had been diagnosed with inflammatory bowel disease (IBD) during 1970-2004. The 311 patients diagnosed with Crohn’s disease and 365 with ulcerative colitis were followed longitudinally through June 2011. The median age at diagnosis of IBD was 33 years.

The prevalence of diagnosed spondyloarthropathy prior to diagnosis of IBD was 1%. The cumulative incidence of spondyloarthropathy following an established IBD diagnosis was 2.3% at 10 years, 4.2% at 20 years, and 7.1% at 30 years. The overall cumulative incidence of ankylosing spondylitis was 0.2% at 10 years, rising to 0.7% at 20 years.

The 10-, 20- and 30-year cumulative incidence rates for spondyloarthropathy after diagnosis of Crohn’s disease were 2.6%, 6.1%, and 9.8%, respectively, as compared with 1.9%, 2.8%, and 4.9% following diagnosis of ulcerative colitis.

Clinical features of spondyloarthropathy that appeared only after diagnosis of IBD included oligoarthritis in 3.1%, polyarthritis in 1.3%, sacroiliitis in 1.6%, psoriasis in 2.2%, uveitis in 2.9%, and plantar fasciitis in 5%.

Dr. Matteson reported having no financial conflicts.

BERLIN – The cumulative incidence of spondyloarthropathy in the first decade after diagnosis of inflammatory bowel disease is about 1 in 50 patients, climbing to 1 in 25 at 20 years and 1 in 14 at 30 years, according to the first population-based study to scrutinize the issue.

The incidence of spondyloarthropathy following diagnosis of ulcerative colitis is about half that seen in Crohn’s disease patients, said Dr. Eric L. Matteson at the Annual European Congress of Rheumatology.

Dr. Matteson, a professor of medicine and chair of the department of rheumatology at the Mayo Clinic, Rochester, Minn., and his coinvestigators analyzed the medical records of Olmsted County, Minn., residents who had been diagnosed with inflammatory bowel disease (IBD) during 1970-2004. The 311 patients diagnosed with Crohn’s disease and 365 with ulcerative colitis were followed longitudinally through June 2011. The median age at diagnosis of IBD was 33 years.

The prevalence of diagnosed spondyloarthropathy prior to diagnosis of IBD was 1%. The cumulative incidence of spondyloarthropathy following an established IBD diagnosis was 2.3% at 10 years, 4.2% at 20 years, and 7.1% at 30 years. The overall cumulative incidence of ankylosing spondylitis was 0.2% at 10 years, rising to 0.7% at 20 years.

The 10-, 20- and 30-year cumulative incidence rates for spondyloarthropathy after diagnosis of Crohn’s disease were 2.6%, 6.1%, and 9.8%, respectively, as compared with 1.9%, 2.8%, and 4.9% following diagnosis of ulcerative colitis.

Clinical features of spondyloarthropathy that appeared only after diagnosis of IBD included oligoarthritis in 3.1%, polyarthritis in 1.3%, sacroiliitis in 1.6%, psoriasis in 2.2%, uveitis in 2.9%, and plantar fasciitis in 5%.

Dr. Matteson reported having no financial conflicts.

BERLIN – The cumulative incidence of spondyloarthropathy in the first decade after diagnosis of inflammatory bowel disease is about 1 in 50 patients, climbing to 1 in 25 at 20 years and 1 in 14 at 30 years, according to the first population-based study to scrutinize the issue.

The incidence of spondyloarthropathy following diagnosis of ulcerative colitis is about half that seen in Crohn’s disease patients, said Dr. Eric L. Matteson at the Annual European Congress of Rheumatology.

Dr. Matteson, a professor of medicine and chair of the department of rheumatology at the Mayo Clinic, Rochester, Minn., and his coinvestigators analyzed the medical records of Olmsted County, Minn., residents who had been diagnosed with inflammatory bowel disease (IBD) during 1970-2004. The 311 patients diagnosed with Crohn’s disease and 365 with ulcerative colitis were followed longitudinally through June 2011. The median age at diagnosis of IBD was 33 years.

The prevalence of diagnosed spondyloarthropathy prior to diagnosis of IBD was 1%. The cumulative incidence of spondyloarthropathy following an established IBD diagnosis was 2.3% at 10 years, 4.2% at 20 years, and 7.1% at 30 years. The overall cumulative incidence of ankylosing spondylitis was 0.2% at 10 years, rising to 0.7% at 20 years.

The 10-, 20- and 30-year cumulative incidence rates for spondyloarthropathy after diagnosis of Crohn’s disease were 2.6%, 6.1%, and 9.8%, respectively, as compared with 1.9%, 2.8%, and 4.9% following diagnosis of ulcerative colitis.

Clinical features of spondyloarthropathy that appeared only after diagnosis of IBD included oligoarthritis in 3.1%, polyarthritis in 1.3%, sacroiliitis in 1.6%, psoriasis in 2.2%, uveitis in 2.9%, and plantar fasciitis in 5%.

Dr. Matteson reported having no financial conflicts.

A Clinical Update Supplement to Pediatric News®.  This supplement was sponsored by Valeant Dermatology 

Click here to view the supplement

Clinical Professor of Dermatology

University of Louisville, KY

A Clinical Update Supplement to Pediatric News®.  This supplement was sponsored by Valeant Dermatology 

Click here to view the supplement

Clinical Professor of Dermatology

University of Louisville, KY

A Clinical Update Supplement to Pediatric News®.  This supplement was sponsored by Valeant Dermatology 

Click here to view the supplement

Clinical Professor of Dermatology

University of Louisville, KY

DANA POINT, CALIF. – No longer just a pipe dream, a novel injectable treatment effective at reducing fat is approaching the end of the drug development process.

The product is a non–animal derived, pharmaceutical grade sodium deoxycholate that "acts much like a detergent. It attacks the cell membranes of fat, disrupting and disintegrating its membranes. Thereafter, fat cell contents are released and the subsequent host response, including inflammation, macrophage scavenging, and subclinical fibrosis, may confer a long-lasting fat-removal effect. It doesn’t shrink the fat cell; it ablates the fat it encounters," said, Dr. Adam M. Rotunda.

Phase III trials of an injectable form of sodium deoxycholate for the reduction of submental fat have begun in the United States, building on the previous success of four phase I, three phase II, and two phase III European studies of the product, known as ATX-101, noted Dr. Rotunda at the Summit in Aesthetic Medicine sponsored by the Skin Disease Education Foundation (SDEF).

In the 1990s, compounded phosphatidylcholine/deoxycholate injections (PC/DC), or lipodissolve, caused harm to some patients because "essentially everything about that experience was wrong: the wrong dose (too much volume, too high concentration); wrong depth (injections at times were too superficial. For example, cellulite, which was erroneously believed to improve from the injections, was injected intradermally); wrong indication (injections in places that shouldn’t have been injected); and wrong formulation," said Dr. Rotunda, who practices dermatology in Newport Beach, Calif. "These compounds were [derived] from animal sources and their sterility and purity could be called into question."

As a result, the FDA and other regulatory agencies around the world warned against or banned the use of unapproved PC/DC for aesthetic purposes. But in 2003, sodium deoxycholate was identified as the major component producing fat cell lysis in compounded PC/DC formulations, said Dr. Rotunda, who is also with the department of dermatology at the University of California, Los Angeles. "It’s taken many years to get that message across," he said.

ATX-101, which is being developed by Kythera Biopharmaceuticals, "is very different from the DC in compounded formulations, which was derived from cow bile," he said. "ATX-101 is being studied for very small volumes of fat relatively small for the submental area, which is really an ideal area to observe the desired effect of this product."

Photos courtesy Kythera

Phase I histology studies revealed that ATX-101 causes rapid adipocytolysis on day 1. On day 28 "there’s septal thickening and macrophage infiltration, which removes cellular debris and triglycerides, cleared via the lymphatic system," Dr. Rotunda said, adding that before and after MRIs have quantitatively confirmed the volume reductions.

Tissue surrounding the fatty treatment area, he continued, "has relatively high protein content. This protein (such as albumin) binds and inactivates deoxycholate, making subcutaneous injections relatively safe and fat specific. There’s an inverse relationship: the higher the protein content of certain tissue, such as muscle, tendon, and dermis, the lower the lytic activity of the deoxycholate. Less activity means less damage to that tissue. In fat, however, we want maximal damage, and it works out well because fat has relatively low protein content."

The administration of ATX-101 involves the use of a 30g needle, a 1-mL syringe, and placement of a temporary tattoo grid to the submental fat to control spacing of injections. "The distribution of the grid and how much is injected depends on the patient’s configuration and neck fat volume," Dr. Rotunda said. During the clinical trials, up to 10 mL of medication was used in each session, with up to four monthly treatments.

Most adverse events in clinical trials to date have been mild to moderate. "This is not a lunchtime procedure," he said. "It will be associated with local swelling and tenderness that may last days to several weeks, depending on the amount of ATX-101 injected or the volume of fat treated."

He concluded his remarks by noting that ATX-101 may become a novel approach that complements but does not compete with other fat-reduction therapies.

Dr. Rotunda disclosed that he, along with Dr. Michael S. Kolodney, are coinventors of ATX-101. He is a consultant to Kythera and holds stock in the company. He also is a consultant to Lithera and Allergan.

SDEF and this news organization are owned by Elsevier.

DANA POINT, CALIF. – No longer just a pipe dream, a novel injectable treatment effective at reducing fat is approaching the end of the drug development process.

The product is a non–animal derived, pharmaceutical grade sodium deoxycholate that "acts much like a detergent. It attacks the cell membranes of fat, disrupting and disintegrating its membranes. Thereafter, fat cell contents are released and the subsequent host response, including inflammation, macrophage scavenging, and subclinical fibrosis, may confer a long-lasting fat-removal effect. It doesn’t shrink the fat cell; it ablates the fat it encounters," said, Dr. Adam M. Rotunda.

Phase III trials of an injectable form of sodium deoxycholate for the reduction of submental fat have begun in the United States, building on the previous success of four phase I, three phase II, and two phase III European studies of the product, known as ATX-101, noted Dr. Rotunda at the Summit in Aesthetic Medicine sponsored by the Skin Disease Education Foundation (SDEF).

In the 1990s, compounded phosphatidylcholine/deoxycholate injections (PC/DC), or lipodissolve, caused harm to some patients because "essentially everything about that experience was wrong: the wrong dose (too much volume, too high concentration); wrong depth (injections at times were too superficial. For example, cellulite, which was erroneously believed to improve from the injections, was injected intradermally); wrong indication (injections in places that shouldn’t have been injected); and wrong formulation," said Dr. Rotunda, who practices dermatology in Newport Beach, Calif. "These compounds were [derived] from animal sources and their sterility and purity could be called into question."

As a result, the FDA and other regulatory agencies around the world warned against or banned the use of unapproved PC/DC for aesthetic purposes. But in 2003, sodium deoxycholate was identified as the major component producing fat cell lysis in compounded PC/DC formulations, said Dr. Rotunda, who is also with the department of dermatology at the University of California, Los Angeles. "It’s taken many years to get that message across," he said.

ATX-101, which is being developed by Kythera Biopharmaceuticals, "is very different from the DC in compounded formulations, which was derived from cow bile," he said. "ATX-101 is being studied for very small volumes of fat relatively small for the submental area, which is really an ideal area to observe the desired effect of this product."

Photos courtesy Kythera

Phase I histology studies revealed that ATX-101 causes rapid adipocytolysis on day 1. On day 28 "there’s septal thickening and macrophage infiltration, which removes cellular debris and triglycerides, cleared via the lymphatic system," Dr. Rotunda said, adding that before and after MRIs have quantitatively confirmed the volume reductions.

Tissue surrounding the fatty treatment area, he continued, "has relatively high protein content. This protein (such as albumin) binds and inactivates deoxycholate, making subcutaneous injections relatively safe and fat specific. There’s an inverse relationship: the higher the protein content of certain tissue, such as muscle, tendon, and dermis, the lower the lytic activity of the deoxycholate. Less activity means less damage to that tissue. In fat, however, we want maximal damage, and it works out well because fat has relatively low protein content."

The administration of ATX-101 involves the use of a 30g needle, a 1-mL syringe, and placement of a temporary tattoo grid to the submental fat to control spacing of injections. "The distribution of the grid and how much is injected depends on the patient’s configuration and neck fat volume," Dr. Rotunda said. During the clinical trials, up to 10 mL of medication was used in each session, with up to four monthly treatments.

Most adverse events in clinical trials to date have been mild to moderate. "This is not a lunchtime procedure," he said. "It will be associated with local swelling and tenderness that may last days to several weeks, depending on the amount of ATX-101 injected or the volume of fat treated."

He concluded his remarks by noting that ATX-101 may become a novel approach that complements but does not compete with other fat-reduction therapies.

Dr. Rotunda disclosed that he, along with Dr. Michael S. Kolodney, are coinventors of ATX-101. He is a consultant to Kythera and holds stock in the company. He also is a consultant to Lithera and Allergan.

SDEF and this news organization are owned by Elsevier.

DANA POINT, CALIF. – No longer just a pipe dream, a novel injectable treatment effective at reducing fat is approaching the end of the drug development process.

The product is a non–animal derived, pharmaceutical grade sodium deoxycholate that "acts much like a detergent. It attacks the cell membranes of fat, disrupting and disintegrating its membranes. Thereafter, fat cell contents are released and the subsequent host response, including inflammation, macrophage scavenging, and subclinical fibrosis, may confer a long-lasting fat-removal effect. It doesn’t shrink the fat cell; it ablates the fat it encounters," said, Dr. Adam M. Rotunda.

Phase III trials of an injectable form of sodium deoxycholate for the reduction of submental fat have begun in the United States, building on the previous success of four phase I, three phase II, and two phase III European studies of the product, known as ATX-101, noted Dr. Rotunda at the Summit in Aesthetic Medicine sponsored by the Skin Disease Education Foundation (SDEF).

In the 1990s, compounded phosphatidylcholine/deoxycholate injections (PC/DC), or lipodissolve, caused harm to some patients because "essentially everything about that experience was wrong: the wrong dose (too much volume, too high concentration); wrong depth (injections at times were too superficial. For example, cellulite, which was erroneously believed to improve from the injections, was injected intradermally); wrong indication (injections in places that shouldn’t have been injected); and wrong formulation," said Dr. Rotunda, who practices dermatology in Newport Beach, Calif. "These compounds were [derived] from animal sources and their sterility and purity could be called into question."

As a result, the FDA and other regulatory agencies around the world warned against or banned the use of unapproved PC/DC for aesthetic purposes. But in 2003, sodium deoxycholate was identified as the major component producing fat cell lysis in compounded PC/DC formulations, said Dr. Rotunda, who is also with the department of dermatology at the University of California, Los Angeles. "It’s taken many years to get that message across," he said.

ATX-101, which is being developed by Kythera Biopharmaceuticals, "is very different from the DC in compounded formulations, which was derived from cow bile," he said. "ATX-101 is being studied for very small volumes of fat relatively small for the submental area, which is really an ideal area to observe the desired effect of this product."

Photos courtesy Kythera

Phase I histology studies revealed that ATX-101 causes rapid adipocytolysis on day 1. On day 28 "there’s septal thickening and macrophage infiltration, which removes cellular debris and triglycerides, cleared via the lymphatic system," Dr. Rotunda said, adding that before and after MRIs have quantitatively confirmed the volume reductions.

Tissue surrounding the fatty treatment area, he continued, "has relatively high protein content. This protein (such as albumin) binds and inactivates deoxycholate, making subcutaneous injections relatively safe and fat specific. There’s an inverse relationship: the higher the protein content of certain tissue, such as muscle, tendon, and dermis, the lower the lytic activity of the deoxycholate. Less activity means less damage to that tissue. In fat, however, we want maximal damage, and it works out well because fat has relatively low protein content."

The administration of ATX-101 involves the use of a 30g needle, a 1-mL syringe, and placement of a temporary tattoo grid to the submental fat to control spacing of injections. "The distribution of the grid and how much is injected depends on the patient’s configuration and neck fat volume," Dr. Rotunda said. During the clinical trials, up to 10 mL of medication was used in each session, with up to four monthly treatments.

Most adverse events in clinical trials to date have been mild to moderate. "This is not a lunchtime procedure," he said. "It will be associated with local swelling and tenderness that may last days to several weeks, depending on the amount of ATX-101 injected or the volume of fat treated."

He concluded his remarks by noting that ATX-101 may become a novel approach that complements but does not compete with other fat-reduction therapies.

Dr. Rotunda disclosed that he, along with Dr. Michael S. Kolodney, are coinventors of ATX-101. He is a consultant to Kythera and holds stock in the company. He also is a consultant to Lithera and Allergan.

SDEF and this news organization are owned by Elsevier.

Physicians who are employed by a hospital or health system may believe they have no power over which EHR their health system chooses or how that EHR will be used. But employed physicians actually can have tremendous impact on how their organizations choose and use EHRs. In this installment, Dr. Skolnik and Dr. Notte talk about what you can do when you're not in charge.

To download the podcast, right-click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Physicians who are employed by a hospital or health system may believe they have no power over which EHR their health system chooses or how that EHR will be used. But employed physicians actually can have tremendous impact on how their organizations choose and use EHRs. In this installment, Dr. Skolnik and Dr. Notte talk about what you can do when you're not in charge.

To download the podcast, right-click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Physicians who are employed by a hospital or health system may believe they have no power over which EHR their health system chooses or how that EHR will be used. But employed physicians actually can have tremendous impact on how their organizations choose and use EHRs. In this installment, Dr. Skolnik and Dr. Notte talk about what you can do when you're not in charge.

To download the podcast, right-click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Pop Warner youth football programs have issued new rules to restrict the amount of contact players can have during practice in an attempt to limit head injuries to young players.

Recent research from Virginia Tech led to this change as the organization – which has more than 250,000 children ages 5 to 15 in its leagues – tries to limit concussions.

Photo ©David Peeters/iStockphoto.com

The study headed by Stefan Duma placed sensors in the helmets of seven youth football players aged 6-8 years during their 2011 season.  He found that 95% of impacts were between 15-20 g’s, what he likened to an “aggressive pillow fight.” But the other 5% were 50-100 g’s, what he said was force like a “car accident,” and the majority of these hits took place during practice.

Research has shown that damage from concussions can be cumulative, so Pop Warner is trying to lessen the number of impacts by reducing incidents in practice.

Read the news story in the NY Times. 

Pop Warner youth football programs have issued new rules to restrict the amount of contact players can have during practice in an attempt to limit head injuries to young players.

Recent research from Virginia Tech led to this change as the organization – which has more than 250,000 children ages 5 to 15 in its leagues – tries to limit concussions.

Photo ©David Peeters/iStockphoto.com

The study headed by Stefan Duma placed sensors in the helmets of seven youth football players aged 6-8 years during their 2011 season.  He found that 95% of impacts were between 15-20 g’s, what he likened to an “aggressive pillow fight.” But the other 5% were 50-100 g’s, what he said was force like a “car accident,” and the majority of these hits took place during practice.

Research has shown that damage from concussions can be cumulative, so Pop Warner is trying to lessen the number of impacts by reducing incidents in practice.

Read the news story in the NY Times. 

Pop Warner youth football programs have issued new rules to restrict the amount of contact players can have during practice in an attempt to limit head injuries to young players.

Recent research from Virginia Tech led to this change as the organization – which has more than 250,000 children ages 5 to 15 in its leagues – tries to limit concussions.

Photo ©David Peeters/iStockphoto.com

The study headed by Stefan Duma placed sensors in the helmets of seven youth football players aged 6-8 years during their 2011 season.  He found that 95% of impacts were between 15-20 g’s, what he likened to an “aggressive pillow fight.” But the other 5% were 50-100 g’s, what he said was force like a “car accident,” and the majority of these hits took place during practice.

Research has shown that damage from concussions can be cumulative, so Pop Warner is trying to lessen the number of impacts by reducing incidents in practice.

Read the news story in the NY Times. 

A supplement to Family Practice News. This supplement was sponsored by National Fisheries Institute.

Topics

• Introduction
• Survey Reveals Knowledge Gap That Inhibits Patient Dialogue
• Barriers to Eating More Seafood
• Conclusions

Faculty/Faculty Disclosure

Jeffrey D. Fisher, MD
Cardiology and Internal Medicine
Weill Cornell Medical College
New York, New York

William Goodnight, MD
Maternal and Fetal Medicine University of North Carolina
Chapel Hill Chapel Hill, North Carolina

Laura Jana, MD
Pediatrician, Health Communicator
Omaha, Nebraska

John La Puma, MD
C.H.E.F. Clinic
Santa Barbara, California

Drs Goodnight, Jana and La Puma have nothing to disclose. Dr Fisher is a consultant to, and has received funding for, clinical grants from National Fisheries Institute.

Copyright © 2012 Elsevier Inc.

A supplement to Family Practice News. This supplement was sponsored by National Fisheries Institute.

Topics

• Introduction
• Survey Reveals Knowledge Gap That Inhibits Patient Dialogue
• Barriers to Eating More Seafood
• Conclusions

Faculty/Faculty Disclosure

Jeffrey D. Fisher, MD
Cardiology and Internal Medicine
Weill Cornell Medical College
New York, New York

William Goodnight, MD
Maternal and Fetal Medicine University of North Carolina
Chapel Hill Chapel Hill, North Carolina

Laura Jana, MD
Pediatrician, Health Communicator
Omaha, Nebraska

John La Puma, MD
C.H.E.F. Clinic
Santa Barbara, California

Drs Goodnight, Jana and La Puma have nothing to disclose. Dr Fisher is a consultant to, and has received funding for, clinical grants from National Fisheries Institute.

Copyright © 2012 Elsevier Inc.

A supplement to Family Practice News. This supplement was sponsored by National Fisheries Institute.

Topics

• Introduction
• Survey Reveals Knowledge Gap That Inhibits Patient Dialogue
• Barriers to Eating More Seafood
• Conclusions

Faculty/Faculty Disclosure

Jeffrey D. Fisher, MD
Cardiology and Internal Medicine
Weill Cornell Medical College
New York, New York

William Goodnight, MD
Maternal and Fetal Medicine University of North Carolina
Chapel Hill Chapel Hill, North Carolina

Laura Jana, MD
Pediatrician, Health Communicator
Omaha, Nebraska

John La Puma, MD
C.H.E.F. Clinic
Santa Barbara, California

Drs Goodnight, Jana and La Puma have nothing to disclose. Dr Fisher is a consultant to, and has received funding for, clinical grants from National Fisheries Institute.

Copyright © 2012 Elsevier Inc.

A pediatric migraine diagnosis starts with a thorough patient history. I start by having the child or adolescent characterize their headache. What is its location, what does it feel like, how long does it last, and is there associated light or noise sensitivity or nausea? For the young children, this is ascertained by asking if they want to be in a dark or quiet room, or if they complain of stomach upset. I also find out about the onset and temporal course of the headache: When did the headaches start, have they become more frequent over time, and has there been a progression in the intensity of the headaches?

It is also quite important to identify headache triggers. I always ask about sleep schedule, eating habits, and fluid intake, as well as potential stress triggers, as these frequently impact on headaches.

It is appropriate to manage children in the primary care setting when they respond to fairly benign, over-the-counter medications, such as ibuprofen or acetaminophen, or triptan medications in the older kids. Refer to a specialist when your patient is not responding to these types of medications, when the headaches are becoming more frequent or severe, or if you have concerns about your patient’s neurologic status.

Also check family history because migraine is strongly genetically based. A family history of migraine headaches coupled with a typical headache character and normal neurologic exam can support your diagnostic suspicion.

In addition to taking a good history, it is critical to perform a detailed neurological examination to exclude any abnormalities that might suggest a more serious underlying cause for the headaches. It is especially important to look at their optic disks to rule out any evidence of increased intracranial pressure or papilledema. If you are unable to perform this type of exam, it is best to refer your patient to an ophthalmologist for a complete ophthalmologic exam. Any focal neurologic abnormalities should prompt a neuroimaging evaluation such as an MRI.

Evaluate for other headache types. Ask about stress triggers. Kids get stress- or tension-type headaches just like adults. When I see children who report frequent headaches that occur predominantly at school and infrequently on weekends, I’m more suspicious of a stress trigger. If headaches occur shortly before mealtimes, they could be caused by transient hypoglycemia and may be prevented by adding a snack or changing the child’s eating schedule.

Another scenario is headaches that occur after football or soccer practice or other vigorous activities. Here, I consider fatigue, dehydration, or perhaps excessive sun exposure as potential triggers. Ask about fluid intake – particularly how much water, not soft drinks, the child drinks. Sodas do not help with dehydration and are frequently loaded with caffeine. Educate them about hydration and how drinking enough fluids can make a huge difference in their headache frequency and severity.

Headaches that occur infrequently or that do not disrupt the child’s typical activities are less worrisome. For example, I am much less concerned when a child or adolescent reports headaches, but they still go outside to play, or go about their regular routine, and stay engaged in family activities.

A headache calendar filled out by the patient, preferably over weeks or months, is very helpful to your headache specialist. This helps us to better characterize the frequency and severity of episodes, what time of day they occur, and any potential precipitating triggers.

I become concerned when headaches get progressively more severe over time, or become more frequent over a short period. Headaches that awaken kids in the middle of the night, or those associated with nausea and vomiting on awakening, may point to a more serious condition, such as a tumor or other expanding mass inside the head causing increased intracranial pressure.

Probably the most over-ordered tests in the children I see with headaches are neuroimaging studies. The majority of young kids with headaches do not require an expensive MRI scan. Most require only a good history and neurologic exam for appropriate diagnosis.

However, a CT or MRI scan is indicated if you suspect a more serious etiology and/or the patient is younger. For example, I am much more likely to get an imaging study when a 3- or 4-year-old child complains of frequent or severe headaches. Historical information will be more limited in the preschoolers because they frequently can’t tell you as much about their headaches, and your examination might be less reliable as well – as the younger kids may be less cooperative and more difficult to examine. I also perform blood tests on some headache patients, looking for infectious, inflammatory, or metabolic derangements as a cause for headaches, but those are infrequently helpful.

Also keep in mind that some headache complaints may be functional in nature. For example, if a particular child gets significant attention with their headaches, there may be some associated secondary gain. A child also might be mimicking adult behavior. If the parents complain frequently about headaches, you might find the kid also complains about headaches.

Although pediatric and adult migraines share many of the same features, the good news is pediatric migraines are frequently not as severe or as protracted in children as they are for adults, and are often highly responsive to treatment. It can be very rewarding managing children with headaches because so many do well.

Dr. Berenson is a pediatric neurologist and section chief of neurology at Children’s Healthcare of Atlanta at Scottish Rite. He is also in private practice at Atlanta Headache Specialists and Pediatric and Adolescent NeuroDevelopmental Associates (PANDA) Neurology. He said he had no relevant financial disclosures.

A pediatric migraine diagnosis starts with a thorough patient history. I start by having the child or adolescent characterize their headache. What is its location, what does it feel like, how long does it last, and is there associated light or noise sensitivity or nausea? For the young children, this is ascertained by asking if they want to be in a dark or quiet room, or if they complain of stomach upset. I also find out about the onset and temporal course of the headache: When did the headaches start, have they become more frequent over time, and has there been a progression in the intensity of the headaches?

It is also quite important to identify headache triggers. I always ask about sleep schedule, eating habits, and fluid intake, as well as potential stress triggers, as these frequently impact on headaches.

It is appropriate to manage children in the primary care setting when they respond to fairly benign, over-the-counter medications, such as ibuprofen or acetaminophen, or triptan medications in the older kids. Refer to a specialist when your patient is not responding to these types of medications, when the headaches are becoming more frequent or severe, or if you have concerns about your patient’s neurologic status.

Also check family history because migraine is strongly genetically based. A family history of migraine headaches coupled with a typical headache character and normal neurologic exam can support your diagnostic suspicion.

In addition to taking a good history, it is critical to perform a detailed neurological examination to exclude any abnormalities that might suggest a more serious underlying cause for the headaches. It is especially important to look at their optic disks to rule out any evidence of increased intracranial pressure or papilledema. If you are unable to perform this type of exam, it is best to refer your patient to an ophthalmologist for a complete ophthalmologic exam. Any focal neurologic abnormalities should prompt a neuroimaging evaluation such as an MRI.

Evaluate for other headache types. Ask about stress triggers. Kids get stress- or tension-type headaches just like adults. When I see children who report frequent headaches that occur predominantly at school and infrequently on weekends, I’m more suspicious of a stress trigger. If headaches occur shortly before mealtimes, they could be caused by transient hypoglycemia and may be prevented by adding a snack or changing the child’s eating schedule.

Another scenario is headaches that occur after football or soccer practice or other vigorous activities. Here, I consider fatigue, dehydration, or perhaps excessive sun exposure as potential triggers. Ask about fluid intake – particularly how much water, not soft drinks, the child drinks. Sodas do not help with dehydration and are frequently loaded with caffeine. Educate them about hydration and how drinking enough fluids can make a huge difference in their headache frequency and severity.

Headaches that occur infrequently or that do not disrupt the child’s typical activities are less worrisome. For example, I am much less concerned when a child or adolescent reports headaches, but they still go outside to play, or go about their regular routine, and stay engaged in family activities.

A headache calendar filled out by the patient, preferably over weeks or months, is very helpful to your headache specialist. This helps us to better characterize the frequency and severity of episodes, what time of day they occur, and any potential precipitating triggers.

I become concerned when headaches get progressively more severe over time, or become more frequent over a short period. Headaches that awaken kids in the middle of the night, or those associated with nausea and vomiting on awakening, may point to a more serious condition, such as a tumor or other expanding mass inside the head causing increased intracranial pressure.

Probably the most over-ordered tests in the children I see with headaches are neuroimaging studies. The majority of young kids with headaches do not require an expensive MRI scan. Most require only a good history and neurologic exam for appropriate diagnosis.

However, a CT or MRI scan is indicated if you suspect a more serious etiology and/or the patient is younger. For example, I am much more likely to get an imaging study when a 3- or 4-year-old child complains of frequent or severe headaches. Historical information will be more limited in the preschoolers because they frequently can’t tell you as much about their headaches, and your examination might be less reliable as well – as the younger kids may be less cooperative and more difficult to examine. I also perform blood tests on some headache patients, looking for infectious, inflammatory, or metabolic derangements as a cause for headaches, but those are infrequently helpful.

Also keep in mind that some headache complaints may be functional in nature. For example, if a particular child gets significant attention with their headaches, there may be some associated secondary gain. A child also might be mimicking adult behavior. If the parents complain frequently about headaches, you might find the kid also complains about headaches.

Although pediatric and adult migraines share many of the same features, the good news is pediatric migraines are frequently not as severe or as protracted in children as they are for adults, and are often highly responsive to treatment. It can be very rewarding managing children with headaches because so many do well.

Dr. Berenson is a pediatric neurologist and section chief of neurology at Children’s Healthcare of Atlanta at Scottish Rite. He is also in private practice at Atlanta Headache Specialists and Pediatric and Adolescent NeuroDevelopmental Associates (PANDA) Neurology. He said he had no relevant financial disclosures.

A pediatric migraine diagnosis starts with a thorough patient history. I start by having the child or adolescent characterize their headache. What is its location, what does it feel like, how long does it last, and is there associated light or noise sensitivity or nausea? For the young children, this is ascertained by asking if they want to be in a dark or quiet room, or if they complain of stomach upset. I also find out about the onset and temporal course of the headache: When did the headaches start, have they become more frequent over time, and has there been a progression in the intensity of the headaches?

It is also quite important to identify headache triggers. I always ask about sleep schedule, eating habits, and fluid intake, as well as potential stress triggers, as these frequently impact on headaches.

It is appropriate to manage children in the primary care setting when they respond to fairly benign, over-the-counter medications, such as ibuprofen or acetaminophen, or triptan medications in the older kids. Refer to a specialist when your patient is not responding to these types of medications, when the headaches are becoming more frequent or severe, or if you have concerns about your patient’s neurologic status.

Also check family history because migraine is strongly genetically based. A family history of migraine headaches coupled with a typical headache character and normal neurologic exam can support your diagnostic suspicion.

In addition to taking a good history, it is critical to perform a detailed neurological examination to exclude any abnormalities that might suggest a more serious underlying cause for the headaches. It is especially important to look at their optic disks to rule out any evidence of increased intracranial pressure or papilledema. If you are unable to perform this type of exam, it is best to refer your patient to an ophthalmologist for a complete ophthalmologic exam. Any focal neurologic abnormalities should prompt a neuroimaging evaluation such as an MRI.

Evaluate for other headache types. Ask about stress triggers. Kids get stress- or tension-type headaches just like adults. When I see children who report frequent headaches that occur predominantly at school and infrequently on weekends, I’m more suspicious of a stress trigger. If headaches occur shortly before mealtimes, they could be caused by transient hypoglycemia and may be prevented by adding a snack or changing the child’s eating schedule.

Another scenario is headaches that occur after football or soccer practice or other vigorous activities. Here, I consider fatigue, dehydration, or perhaps excessive sun exposure as potential triggers. Ask about fluid intake – particularly how much water, not soft drinks, the child drinks. Sodas do not help with dehydration and are frequently loaded with caffeine. Educate them about hydration and how drinking enough fluids can make a huge difference in their headache frequency and severity.

Headaches that occur infrequently or that do not disrupt the child’s typical activities are less worrisome. For example, I am much less concerned when a child or adolescent reports headaches, but they still go outside to play, or go about their regular routine, and stay engaged in family activities.

A headache calendar filled out by the patient, preferably over weeks or months, is very helpful to your headache specialist. This helps us to better characterize the frequency and severity of episodes, what time of day they occur, and any potential precipitating triggers.

I become concerned when headaches get progressively more severe over time, or become more frequent over a short period. Headaches that awaken kids in the middle of the night, or those associated with nausea and vomiting on awakening, may point to a more serious condition, such as a tumor or other expanding mass inside the head causing increased intracranial pressure.

Probably the most over-ordered tests in the children I see with headaches are neuroimaging studies. The majority of young kids with headaches do not require an expensive MRI scan. Most require only a good history and neurologic exam for appropriate diagnosis.

However, a CT or MRI scan is indicated if you suspect a more serious etiology and/or the patient is younger. For example, I am much more likely to get an imaging study when a 3- or 4-year-old child complains of frequent or severe headaches. Historical information will be more limited in the preschoolers because they frequently can’t tell you as much about their headaches, and your examination might be less reliable as well – as the younger kids may be less cooperative and more difficult to examine. I also perform blood tests on some headache patients, looking for infectious, inflammatory, or metabolic derangements as a cause for headaches, but those are infrequently helpful.

Also keep in mind that some headache complaints may be functional in nature. For example, if a particular child gets significant attention with their headaches, there may be some associated secondary gain. A child also might be mimicking adult behavior. If the parents complain frequently about headaches, you might find the kid also complains about headaches.

Although pediatric and adult migraines share many of the same features, the good news is pediatric migraines are frequently not as severe or as protracted in children as they are for adults, and are often highly responsive to treatment. It can be very rewarding managing children with headaches because so many do well.

Dr. Berenson is a pediatric neurologist and section chief of neurology at Children’s Healthcare of Atlanta at Scottish Rite. He is also in private practice at Atlanta Headache Specialists and Pediatric and Adolescent NeuroDevelopmental Associates (PANDA) Neurology. He said he had no relevant financial disclosures.