Sherry Boschert

SAN FRANCISCO – The current savior of dermatologists who treat pediatric warts is immunotherapy with Candida antigen, according to Dr. Sheila Fallon Friedlander.

"Warts are either the bane of your existence or the bread and butter," she said at the Women’s & Pediatric Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). Candida antigen injections are not her first-line treatment choice, and injections aren’t desirable for some warts (such as those on the face), but she said Candida antigen is effective.

Photo courtesy Dr. Sheila Fallon Friedlander

"There’s a lot of experience out there now. Candida truly does work, but you’ve got to be aware of side effects," said Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego.

Articles in the medical literature suggest injecting up to 0.3 cc of Candida antigen directly into the substance of the largest wart. "Who are they kidding?" she scoffed. The wart would have to be a giant one to hold that much. "Get what you can directly into the wart," she suggested.

There’s controversy about whether it’s most important to get Candida antigen into the wart, the dermis, or both. Dr. Friedlander said she tries to do both. There’s no need to treat all warts; usually injecting one to three will suffice. Repeat the treatment every 3 weeks for a total of three to five treatments, she said.

One study found a relapse rate of 5% after 2 years, compared with relapse rates of 39% with cryotherapy and 10% with laser therapy (Arch. Dermatol. 2001;137:451-5).

Be sure to warn the family that the treatment may cause discomfort, redness, and swelling. Dr. Friedlander said she is cautious about injecting distal fingers because of a report of complications from Candida antigen injections of a patient’s distal left thumb and the distal subungual area of the left index finger. Within 24 hours the patient had a painful purple index finger with tremendous edema requiring incision (Dermatitis 2005;16:38-40).

To choose the best treatment for pediatric warts, consider some key questions, she advised. Are the lesions truly warts or something else (molluscum or Spitz nevi)? Is the patient well or immunocompromised? Are the warts large or small? Do they create a cosmetic problem? Most importantly, does the patient care that the warts are there?

Unlike acne, which raises concerns about scarring, pediatric warts usually disappear over time without leaving a scar. "Remember, you are the patient’s advocate," which sometimes means clashing with parents over whether to treat a wart, she said.

If you pursue treatment, design a plan the family can live with. Some want only gentle, organic products while others want to take a blowtorch to warts.

Her favorite approach is to start with cryotherapy "for the brave," and in between cryotherapy treatments, have the family use "the triple whammy" – topical salicylic acid, Mediplast, and duct tape, she said. If this isn’t working, and the family wants more, she quickly switches to intralesional Candida for multiple warts. For facial warts, however, she said she prefers tretinoin cream, and for periungual warts she prefers cantharidin (blister beetle extract).

Dr. Friedlander recommended a recent review in the May/June 2011 issue of Pediatric Dermatology of these and other treatments for warts that include a complex algorithm for choosing therapies (Ped. Derm. 2011;28:217-29).

A separate prospective randomized trial reported that a triple combination of cantharidin, podophyllotoxin, and salicylic acid worked better than cryotherapy to remove plantar warts (J. Eur. Acad. Dermatol. Venereol. 2011 July 26 [doi:10.1111/j.1468-3083.2011.04186.x]).

Some physicians are using photodynamic therapy to treat warts, but "I think that’s a sledgehammer approach," she said. A Cochrane review of 60 randomized controlled trials reported that topical salicylic acid has the best evidence for treating warts, but that review did not include Candida antigen, she added (Cochrane Database Syst. Rev. 2006 July 19;3:CD001781).

Dr. Friedlander said she has been a speaker, consultant, or researcher for Pierre-Favre, Onset Therapeutics, Ortho/Johnson & Johnson, and Galderma.

SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – The current savior of dermatologists who treat pediatric warts is immunotherapy with Candida antigen, according to Dr. Sheila Fallon Friedlander.

"Warts are either the bane of your existence or the bread and butter," she said at the Women’s & Pediatric Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). Candida antigen injections are not her first-line treatment choice, and injections aren’t desirable for some warts (such as those on the face), but she said Candida antigen is effective.

Photo courtesy Dr. Sheila Fallon Friedlander

"There’s a lot of experience out there now. Candida truly does work, but you’ve got to be aware of side effects," said Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego.

Articles in the medical literature suggest injecting up to 0.3 cc of Candida antigen directly into the substance of the largest wart. "Who are they kidding?" she scoffed. The wart would have to be a giant one to hold that much. "Get what you can directly into the wart," she suggested.

There’s controversy about whether it’s most important to get Candida antigen into the wart, the dermis, or both. Dr. Friedlander said she tries to do both. There’s no need to treat all warts; usually injecting one to three will suffice. Repeat the treatment every 3 weeks for a total of three to five treatments, she said.

One study found a relapse rate of 5% after 2 years, compared with relapse rates of 39% with cryotherapy and 10% with laser therapy (Arch. Dermatol. 2001;137:451-5).

Be sure to warn the family that the treatment may cause discomfort, redness, and swelling. Dr. Friedlander said she is cautious about injecting distal fingers because of a report of complications from Candida antigen injections of a patient’s distal left thumb and the distal subungual area of the left index finger. Within 24 hours the patient had a painful purple index finger with tremendous edema requiring incision (Dermatitis 2005;16:38-40).

To choose the best treatment for pediatric warts, consider some key questions, she advised. Are the lesions truly warts or something else (molluscum or Spitz nevi)? Is the patient well or immunocompromised? Are the warts large or small? Do they create a cosmetic problem? Most importantly, does the patient care that the warts are there?

Unlike acne, which raises concerns about scarring, pediatric warts usually disappear over time without leaving a scar. "Remember, you are the patient’s advocate," which sometimes means clashing with parents over whether to treat a wart, she said.

If you pursue treatment, design a plan the family can live with. Some want only gentle, organic products while others want to take a blowtorch to warts.

Her favorite approach is to start with cryotherapy "for the brave," and in between cryotherapy treatments, have the family use "the triple whammy" – topical salicylic acid, Mediplast, and duct tape, she said. If this isn’t working, and the family wants more, she quickly switches to intralesional Candida for multiple warts. For facial warts, however, she said she prefers tretinoin cream, and for periungual warts she prefers cantharidin (blister beetle extract).

Dr. Friedlander recommended a recent review in the May/June 2011 issue of Pediatric Dermatology of these and other treatments for warts that include a complex algorithm for choosing therapies (Ped. Derm. 2011;28:217-29).

A separate prospective randomized trial reported that a triple combination of cantharidin, podophyllotoxin, and salicylic acid worked better than cryotherapy to remove plantar warts (J. Eur. Acad. Dermatol. Venereol. 2011 July 26 [doi:10.1111/j.1468-3083.2011.04186.x]).

Some physicians are using photodynamic therapy to treat warts, but "I think that’s a sledgehammer approach," she said. A Cochrane review of 60 randomized controlled trials reported that topical salicylic acid has the best evidence for treating warts, but that review did not include Candida antigen, she added (Cochrane Database Syst. Rev. 2006 July 19;3:CD001781).

Dr. Friedlander said she has been a speaker, consultant, or researcher for Pierre-Favre, Onset Therapeutics, Ortho/Johnson & Johnson, and Galderma.

SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – The current savior of dermatologists who treat pediatric warts is immunotherapy with Candida antigen, according to Dr. Sheila Fallon Friedlander.

"Warts are either the bane of your existence or the bread and butter," she said at the Women’s & Pediatric Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). Candida antigen injections are not her first-line treatment choice, and injections aren’t desirable for some warts (such as those on the face), but she said Candida antigen is effective.

Photo courtesy Dr. Sheila Fallon Friedlander

"There’s a lot of experience out there now. Candida truly does work, but you’ve got to be aware of side effects," said Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego.

Articles in the medical literature suggest injecting up to 0.3 cc of Candida antigen directly into the substance of the largest wart. "Who are they kidding?" she scoffed. The wart would have to be a giant one to hold that much. "Get what you can directly into the wart," she suggested.

There’s controversy about whether it’s most important to get Candida antigen into the wart, the dermis, or both. Dr. Friedlander said she tries to do both. There’s no need to treat all warts; usually injecting one to three will suffice. Repeat the treatment every 3 weeks for a total of three to five treatments, she said.

One study found a relapse rate of 5% after 2 years, compared with relapse rates of 39% with cryotherapy and 10% with laser therapy (Arch. Dermatol. 2001;137:451-5).

Be sure to warn the family that the treatment may cause discomfort, redness, and swelling. Dr. Friedlander said she is cautious about injecting distal fingers because of a report of complications from Candida antigen injections of a patient’s distal left thumb and the distal subungual area of the left index finger. Within 24 hours the patient had a painful purple index finger with tremendous edema requiring incision (Dermatitis 2005;16:38-40).

To choose the best treatment for pediatric warts, consider some key questions, she advised. Are the lesions truly warts or something else (molluscum or Spitz nevi)? Is the patient well or immunocompromised? Are the warts large or small? Do they create a cosmetic problem? Most importantly, does the patient care that the warts are there?

Unlike acne, which raises concerns about scarring, pediatric warts usually disappear over time without leaving a scar. "Remember, you are the patient’s advocate," which sometimes means clashing with parents over whether to treat a wart, she said.

If you pursue treatment, design a plan the family can live with. Some want only gentle, organic products while others want to take a blowtorch to warts.

Her favorite approach is to start with cryotherapy "for the brave," and in between cryotherapy treatments, have the family use "the triple whammy" – topical salicylic acid, Mediplast, and duct tape, she said. If this isn’t working, and the family wants more, she quickly switches to intralesional Candida for multiple warts. For facial warts, however, she said she prefers tretinoin cream, and for periungual warts she prefers cantharidin (blister beetle extract).

Dr. Friedlander recommended a recent review in the May/June 2011 issue of Pediatric Dermatology of these and other treatments for warts that include a complex algorithm for choosing therapies (Ped. Derm. 2011;28:217-29).

A separate prospective randomized trial reported that a triple combination of cantharidin, podophyllotoxin, and salicylic acid worked better than cryotherapy to remove plantar warts (J. Eur. Acad. Dermatol. Venereol. 2011 July 26 [doi:10.1111/j.1468-3083.2011.04186.x]).

Some physicians are using photodynamic therapy to treat warts, but "I think that’s a sledgehammer approach," she said. A Cochrane review of 60 randomized controlled trials reported that topical salicylic acid has the best evidence for treating warts, but that review did not include Candida antigen, she added (Cochrane Database Syst. Rev. 2006 July 19;3:CD001781).

Dr. Friedlander said she has been a speaker, consultant, or researcher for Pierre-Favre, Onset Therapeutics, Ortho/Johnson & Johnson, and Galderma.

SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – One in 100 people in the United States has celiac disease, and 25% will develop dermatitis herpetiformis Duhring, a cutaneous manifestation of the disease.

Clinical diagnosis of dermatitis herpetiformis Duhring, also known as Duhring’s disease, is difficult, but skin biopsy and direct immunofluorescence can help make the diagnosis. Look for antibodies against gliadin, endomysium, and transglutaminase, Dr. Magdalene A. Dohil said at the seminar, sponsored by Skin Disease Education Foundation (SDEF).

Dermatitis herpetiformis Duhring is uncommon in children, with only 5% of cases appearing in patients younger than 7 years. It more typically presents in the fourth decade of life.

Celiac disease is very common, though, and mucocutaneous manifestations may point to the diagnosis, said Dr. Dohil of the University of California, San Diego.

Approximately 1% of the U.S. population has this genetically determined intolerance to gluten, and 74% of people with celiac disease will have cutaneous manifestations – most commonly xerosis, which often causes pruritus. Mucosal manifestations occur in 27% of patients, nail manifestations in 20%, and hair manifestations in 7%. Mucosal findings are most likely in patients with longer duration of celiac disease. Cutaneous findings tend to be non-specific and do not help much in diagnosing celiac disease.

The gold standard for diagnosing celiac disease remains a small bowel biopsy showing villous atrophy, crypt hyperplasia, and lymphocytic infiltrate, according to Dr. Dohil. Because patients with celiac disease have increased risk for osteoporosis and intestinal lymphoma, it’s important to screen adult patients for these problems.

Treating celiac disease involves a lifelong gluten-free diet. Treat dermatitis herpetiformis Duhring with a gluten-free diet and dapsone, she said.

A connection between skin and gut can be found in many diseases, disorders, syndromes, and structural epithelial defects, she noted. GI symptoms affect 58% of children with epidermolysis bullosa. Dysphagia (even to saliva) occurs in 76% of patients with recessive dystrophic epidermolysis bullosa (RDEB) and in 15% of patients with junctional epidermolysis bullosa (JEB). Lingual adhesions and microstomia can be seen. In the esophagus, epidermolysis bullosa can affect anatomical motility though strictures, herniations, atony, reflux, and other problems. Patients are at high risk for nutritional difficulties; 77% of patients with RDEB and 57% with JEB are underweight. Because of the impact of the nutritional imbalance on wound healing, more than half of patients with RDEB require gastrostomy.

"It is vital to address these adequately since any negative nutritional balance has a major impact on wound healing ability," she added.

Mastocytosis can have multisystem involvement including the skin. In the GI system, mastocytosis can lead to nausea and vomiting, diarrhea, abdominal cramping, ulcerative disease, and GI tract bleeding.

Blue-rubber bleb nevus syndrome, or "bean syndrome," consists of multifocal venous malformations in the skin and GI tract. On histology, the endothelium is intact but there is insufficient smooth muscle. Patients have a lifelong tendency toward bleeding and chronic anemia with increased risk for blood transfusion due to hepatitis or allosensitization.

The mucocutaneous pigmentation due to melanin deposition of Peutz-Jeghers syndrome is associated with increased morbidity from intestinal polyps and increased risk of invasive carcinoma. Among patients with Peutz-Jeghers syndrome, cancer develops primarily in the colon, the breast, the stomach, and the small intestine, among other locations.

GI symptoms develop in 50%-85% of patients with Henoch-Schönlein purpura. Multiple irregular ulcers, mucosal redness, duodenal petechia, and hematoma-like protrusions are most common.

Imaging screening for extracutaneous involvement of hemangioma of infancy is recommended if there are more than five cutaneous hemangiomas, one solitary large segmental hemangioma, or PHACES syndrome (the presence of posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities, and a sternal cleft). These extracutaneous lesions present mainly in the liver and GI tract.

Asymptomatic inflammatory bowel disease can present with mucocutaneous findings including skin tags, fistulas, fissures, or abscesses in the perianal and genital areas of 60%-82% of patients. These often will precede GI complaints in 25%-30% of cases, Dr. Dohil said. Oral lesions occur in 6%-20% of all patients with inflammatory bowel disease but in pediatric patients can be found in up to 80% with Crohn’s disease and 41% with ulcerative colitis.

Multiple skin lesions on the lower extremities are possible with pyoderma gangrenosum, an extraintestinal complication of inflammatory bowel disease. This is more common in patients of African-American descent with a family history of ulcerative colitis, or those with pancolitis at initial presentation. Avoid aggressive debridement in these patients because pyoderma gangrenosum has a predilection for areas of trauma, she advised. Treat with topical 0.5% nicotine cream, high-dose corticosteroids, or other immunomodulatory drugs.

Nearly all patients with systemic scleroderma will have esophageal disease, and extraesophageal manifestations can appear as mouth ulcers, chronic cough, and recurrent pneumonia, she reported.

Dr. Dohil said she had no relevant conflicts of interest. Her husband owns a patent for a new treatment for eosinophilic esophagitis, but she did not discuss this treatment. SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – One in 100 people in the United States has celiac disease, and 25% will develop dermatitis herpetiformis Duhring, a cutaneous manifestation of the disease.

Clinical diagnosis of dermatitis herpetiformis Duhring, also known as Duhring’s disease, is difficult, but skin biopsy and direct immunofluorescence can help make the diagnosis. Look for antibodies against gliadin, endomysium, and transglutaminase, Dr. Magdalene A. Dohil said at the seminar, sponsored by Skin Disease Education Foundation (SDEF).

Dermatitis herpetiformis Duhring is uncommon in children, with only 5% of cases appearing in patients younger than 7 years. It more typically presents in the fourth decade of life.

Celiac disease is very common, though, and mucocutaneous manifestations may point to the diagnosis, said Dr. Dohil of the University of California, San Diego.

Approximately 1% of the U.S. population has this genetically determined intolerance to gluten, and 74% of people with celiac disease will have cutaneous manifestations – most commonly xerosis, which often causes pruritus. Mucosal manifestations occur in 27% of patients, nail manifestations in 20%, and hair manifestations in 7%. Mucosal findings are most likely in patients with longer duration of celiac disease. Cutaneous findings tend to be non-specific and do not help much in diagnosing celiac disease.

The gold standard for diagnosing celiac disease remains a small bowel biopsy showing villous atrophy, crypt hyperplasia, and lymphocytic infiltrate, according to Dr. Dohil. Because patients with celiac disease have increased risk for osteoporosis and intestinal lymphoma, it’s important to screen adult patients for these problems.

Treating celiac disease involves a lifelong gluten-free diet. Treat dermatitis herpetiformis Duhring with a gluten-free diet and dapsone, she said.

A connection between skin and gut can be found in many diseases, disorders, syndromes, and structural epithelial defects, she noted. GI symptoms affect 58% of children with epidermolysis bullosa. Dysphagia (even to saliva) occurs in 76% of patients with recessive dystrophic epidermolysis bullosa (RDEB) and in 15% of patients with junctional epidermolysis bullosa (JEB). Lingual adhesions and microstomia can be seen. In the esophagus, epidermolysis bullosa can affect anatomical motility though strictures, herniations, atony, reflux, and other problems. Patients are at high risk for nutritional difficulties; 77% of patients with RDEB and 57% with JEB are underweight. Because of the impact of the nutritional imbalance on wound healing, more than half of patients with RDEB require gastrostomy.

"It is vital to address these adequately since any negative nutritional balance has a major impact on wound healing ability," she added.

Mastocytosis can have multisystem involvement including the skin. In the GI system, mastocytosis can lead to nausea and vomiting, diarrhea, abdominal cramping, ulcerative disease, and GI tract bleeding.

Blue-rubber bleb nevus syndrome, or "bean syndrome," consists of multifocal venous malformations in the skin and GI tract. On histology, the endothelium is intact but there is insufficient smooth muscle. Patients have a lifelong tendency toward bleeding and chronic anemia with increased risk for blood transfusion due to hepatitis or allosensitization.

The mucocutaneous pigmentation due to melanin deposition of Peutz-Jeghers syndrome is associated with increased morbidity from intestinal polyps and increased risk of invasive carcinoma. Among patients with Peutz-Jeghers syndrome, cancer develops primarily in the colon, the breast, the stomach, and the small intestine, among other locations.

GI symptoms develop in 50%-85% of patients with Henoch-Schönlein purpura. Multiple irregular ulcers, mucosal redness, duodenal petechia, and hematoma-like protrusions are most common.

Imaging screening for extracutaneous involvement of hemangioma of infancy is recommended if there are more than five cutaneous hemangiomas, one solitary large segmental hemangioma, or PHACES syndrome (the presence of posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities, and a sternal cleft). These extracutaneous lesions present mainly in the liver and GI tract.

Asymptomatic inflammatory bowel disease can present with mucocutaneous findings including skin tags, fistulas, fissures, or abscesses in the perianal and genital areas of 60%-82% of patients. These often will precede GI complaints in 25%-30% of cases, Dr. Dohil said. Oral lesions occur in 6%-20% of all patients with inflammatory bowel disease but in pediatric patients can be found in up to 80% with Crohn’s disease and 41% with ulcerative colitis.

Multiple skin lesions on the lower extremities are possible with pyoderma gangrenosum, an extraintestinal complication of inflammatory bowel disease. This is more common in patients of African-American descent with a family history of ulcerative colitis, or those with pancolitis at initial presentation. Avoid aggressive debridement in these patients because pyoderma gangrenosum has a predilection for areas of trauma, she advised. Treat with topical 0.5% nicotine cream, high-dose corticosteroids, or other immunomodulatory drugs.

Nearly all patients with systemic scleroderma will have esophageal disease, and extraesophageal manifestations can appear as mouth ulcers, chronic cough, and recurrent pneumonia, she reported.

Dr. Dohil said she had no relevant conflicts of interest. Her husband owns a patent for a new treatment for eosinophilic esophagitis, but she did not discuss this treatment. SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO – One in 100 people in the United States has celiac disease, and 25% will develop dermatitis herpetiformis Duhring, a cutaneous manifestation of the disease.

Clinical diagnosis of dermatitis herpetiformis Duhring, also known as Duhring’s disease, is difficult, but skin biopsy and direct immunofluorescence can help make the diagnosis. Look for antibodies against gliadin, endomysium, and transglutaminase, Dr. Magdalene A. Dohil said at the seminar, sponsored by Skin Disease Education Foundation (SDEF).

Dermatitis herpetiformis Duhring is uncommon in children, with only 5% of cases appearing in patients younger than 7 years. It more typically presents in the fourth decade of life.

Celiac disease is very common, though, and mucocutaneous manifestations may point to the diagnosis, said Dr. Dohil of the University of California, San Diego.

Approximately 1% of the U.S. population has this genetically determined intolerance to gluten, and 74% of people with celiac disease will have cutaneous manifestations – most commonly xerosis, which often causes pruritus. Mucosal manifestations occur in 27% of patients, nail manifestations in 20%, and hair manifestations in 7%. Mucosal findings are most likely in patients with longer duration of celiac disease. Cutaneous findings tend to be non-specific and do not help much in diagnosing celiac disease.

The gold standard for diagnosing celiac disease remains a small bowel biopsy showing villous atrophy, crypt hyperplasia, and lymphocytic infiltrate, according to Dr. Dohil. Because patients with celiac disease have increased risk for osteoporosis and intestinal lymphoma, it’s important to screen adult patients for these problems.

Treating celiac disease involves a lifelong gluten-free diet. Treat dermatitis herpetiformis Duhring with a gluten-free diet and dapsone, she said.

A connection between skin and gut can be found in many diseases, disorders, syndromes, and structural epithelial defects, she noted. GI symptoms affect 58% of children with epidermolysis bullosa. Dysphagia (even to saliva) occurs in 76% of patients with recessive dystrophic epidermolysis bullosa (RDEB) and in 15% of patients with junctional epidermolysis bullosa (JEB). Lingual adhesions and microstomia can be seen. In the esophagus, epidermolysis bullosa can affect anatomical motility though strictures, herniations, atony, reflux, and other problems. Patients are at high risk for nutritional difficulties; 77% of patients with RDEB and 57% with JEB are underweight. Because of the impact of the nutritional imbalance on wound healing, more than half of patients with RDEB require gastrostomy.

"It is vital to address these adequately since any negative nutritional balance has a major impact on wound healing ability," she added.

Mastocytosis can have multisystem involvement including the skin. In the GI system, mastocytosis can lead to nausea and vomiting, diarrhea, abdominal cramping, ulcerative disease, and GI tract bleeding.

Blue-rubber bleb nevus syndrome, or "bean syndrome," consists of multifocal venous malformations in the skin and GI tract. On histology, the endothelium is intact but there is insufficient smooth muscle. Patients have a lifelong tendency toward bleeding and chronic anemia with increased risk for blood transfusion due to hepatitis or allosensitization.

The mucocutaneous pigmentation due to melanin deposition of Peutz-Jeghers syndrome is associated with increased morbidity from intestinal polyps and increased risk of invasive carcinoma. Among patients with Peutz-Jeghers syndrome, cancer develops primarily in the colon, the breast, the stomach, and the small intestine, among other locations.

GI symptoms develop in 50%-85% of patients with Henoch-Schönlein purpura. Multiple irregular ulcers, mucosal redness, duodenal petechia, and hematoma-like protrusions are most common.

Imaging screening for extracutaneous involvement of hemangioma of infancy is recommended if there are more than five cutaneous hemangiomas, one solitary large segmental hemangioma, or PHACES syndrome (the presence of posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities, and a sternal cleft). These extracutaneous lesions present mainly in the liver and GI tract.

Asymptomatic inflammatory bowel disease can present with mucocutaneous findings including skin tags, fistulas, fissures, or abscesses in the perianal and genital areas of 60%-82% of patients. These often will precede GI complaints in 25%-30% of cases, Dr. Dohil said. Oral lesions occur in 6%-20% of all patients with inflammatory bowel disease but in pediatric patients can be found in up to 80% with Crohn’s disease and 41% with ulcerative colitis.

Multiple skin lesions on the lower extremities are possible with pyoderma gangrenosum, an extraintestinal complication of inflammatory bowel disease. This is more common in patients of African-American descent with a family history of ulcerative colitis, or those with pancolitis at initial presentation. Avoid aggressive debridement in these patients because pyoderma gangrenosum has a predilection for areas of trauma, she advised. Treat with topical 0.5% nicotine cream, high-dose corticosteroids, or other immunomodulatory drugs.

Nearly all patients with systemic scleroderma will have esophageal disease, and extraesophageal manifestations can appear as mouth ulcers, chronic cough, and recurrent pneumonia, she reported.

Dr. Dohil said she had no relevant conflicts of interest. Her husband owns a patent for a new treatment for eosinophilic esophagitis, but she did not discuss this treatment. SDEF and this news organization are owned by Elsevier.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS (EGMN) – Results of two randomized controlled trials appear to solidify the safety of remote monitoring of implantable cardioverter defibrillators, and one of the studies showed a significant decrease in the number of patients receiving inappropriate shocks in the remote-monitoring group.

Manufacturers of ICDs currently recommend in-clinic follow-up every 3 months to detect clinical events or device malfunctions. With increasing numbers of people receiving ICDs to prevent sudden cardiac death from rhythm disturbances, investigators are testing ways to avoid the time constraints of so many in-clinic visits by remotely transmitting information from the device via telephone from the patient’s home. Most ICDs now have this capability.

The two randomized controlled trials support findings from patient registries in Europe and in the United States, where remote monitoring is common.

In the yearlong Evaluation of Tele Follow-up (EVATEL) trial, 1,501 patients at 30 French centers were randomized to in-clinic follow-up at the implant center every 3 months or to remote transmission of data to the implant center every 3 months. The study included four types of ICDs.

Results showed no significant difference between groups in the time to first major cardiovascular event or in the rates of major cardiovascular events (death from all causes, cardiovascular-related hospitalization, or inappropriate or ineffective shocks), Dr. Philippe Mabo and his associates reported at the annual congress of the European Society of Cardiology .

Rates of this composite end point were 28% in the remote-monitoring group and 29% in the control group in an intent-to-treat analysis, showing that home monitoring was not inferior to in-office monitoring. In a per-protocol analysis, the primary end points were seen in 28% and 30% of the groups, respectively, but the confidence interval was too wide to claim that there was no significant difference between groups, said Dr. Mabo of Rennes (France) University Hospital.

The trial could not demonstrate an impact on preventing major clinical events, but it did reinforce the safety of remote monitoring, he said.

The study also found a significant 27% reduction in the number of inappropriate shocks delivered by the ICDs, from approximately 8% in the control group to 5% in the remote-monitoring group.

Among several weaknesses of the study, there were no interventions planned in response to monitoring, said Dr. Angelo Auricchio, who commented on the study in the presentation session. Using the data to intervene in problems with ICDs is "the greatest advantage" of the technology, so it is not surprising that the EVATEL study did not show a major impact on cardiovascular end points, said Dr. Auricchio of the Fondazione Cardiocentro Ticino, Lugano, Switzerland.

In addition, the number of patients in the study did not quite reach the calculated sample size required to demonstrate noninferiority of home ICD monitoring.

The separate Effectiveness and Cost of ICD Follow-up Schedule with Telecardiology (ECOST) study randomized 433 patients in 43 French centers to daily remote monitoring using the Biotronik Home Monitoring system or quarterly in-clinic follow-up for 27 months.

Rates of a combined end point of mortality, major cardiovascular events, or major device-related adverse events did not differ significantly between groups, affecting 38% of the remote-monitoring group and 42% of the control group, Dr. Salem Kacet and his associates reported.

Among secondary outcomes, the remote monitoring group showed a significant 52% reduction in the number of patients receiving inappropriate shocks (5% in the remote-monitoring group and 10% in the control group), Dr. Kacet of the University of Lille, France.

The number of patients hospitalized because of inappropriate shocks also was significantly lower in the remote-monitoring group (3) compared with the control group (11).

A significant 76% decrease in the total number of charged shocks in the remote-monitoring group (499 shocks), compared with the control group (2,081 shocks) translated into a significant impact on battery longevity. Among patients with more than one charged shock during the study, ICD battery capacity depleted 0.07% per day in the remote-monitoring group and 0.18% per day in the control group, so that 3 patients in the remote-monitoring group and 11 in the control group had ICDs left with less than 50% of battery capacity.

The number of delivered shocks was significantly lower in the remote-monitoring group (193) than in the control group (657), a significant 71% difference.

Quality-of-life scores on the Short Form-36 were similar between groups.

The relatively long-term follow-up of the ECOST study supports the safety and noninferiority of remote monitoring of ICDs, and shows that home monitoring could reduce inappropriate shocks, charged shocks and delivered shocks, thus prolonging battery longevity and potentially delaying the need for battery replacement surgery, as well as decreasing associated risks.

"This is a very important observation," said Dr. Sidney Goldstein of Henry Ford Hospital, Detroit, who co-moderated a press briefing that included the two studies.

Dr. Kacet said the investigators will perform a secondary analysis of costs in the two monitoring groups soon. The cost analysis is important, because it is not known if the cost of resources to analyze the increased data from home monitoring outweighs potential financial benefits from reduced shocks and prolonged battery life, Dr. Gordon F. Tomaselli said in an interview.

U.S. patients with ICDs often have more than one doctor managing their care. If home monitoring can eliminate some visits to their primary care doctor, cardiologist, or electrophysiologist, this could make an important difference in convenience and costs, said Dr. Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins University, Baltimore.

"We use remote monitoring now for people who find it difficult to get back to our arrhythmia center to be evaluated. I don’t think [these studies] will change things too much in the way of what we do," he said. "For people who are very close, it’s oftentimes not inconvenient for them to come see us face-to-face."

The studies also add to evidence from two previous randomized controlled trials that relied on surrogate end points to evaluate remote ICD monitoring. One study of 1,339 patients reported a 45% reduction in in-office device evaluations among remotely monitored patients without affecting safety (Circulation 2010;122:325-32). A separate study of 1,997 patients found that remote monitoring reduced the time from an ICD-related event to a clinical decision from 22 days to 5 days, and reduced the length of cardiovascular-related hospital stays from an average of 4.0 days to 3.3 days (J. Am. Coll. Cardiol. 2011;57:1181-9).

Biotronik funded the ECOST study. Dr. Kacet has received research funding from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, Sorin Group, Bayer, Boehringer-Ingelheim, Meda, and Sanofi-Aventis. Dr. Mabo has been a speaker, consultant, or investigator for all five companies making implantable cardiac devices. Dr. Auricchio has been a consultant to all companies making implantable cardiac devices. Dr. Tomaselli said he has no conflicts of interest.

PARIS – Postpartum depression is such a common problem that it’s surprising there are so few randomized, controlled studies comparing drug therapy versus nondrug treatment options. Many women with postpartum depression don’t seek treatment, some are treated only with psychotherapy because of concerns regarding pharmacotherapy, and others are treated with antidepressants alone.

Israeli investigators conducted a small, randomized, controlled study in 40 women with mild to moderate postpartum depression lasting 6 months or longer. They expected psychotherapy plus the antidepressant sertraline to be more effective than psychotherapy alone, but they were surprised to find no additional benefit from the drug.

Response rates were 70% in women who received both psychotherapy and sertraline and 55% in those who got psychotherapy and a placebo. This was not a statistically significant difference at a P value of 0.33, Dr. Miki Bloch and his associates reported at the annual congress of the European College of Neuropsychopharmacology. The rates of remission after 8 weeks of treatment were 65% in the combination therapy group and 50% in the psychotherapy plus placebo group, which also was not a significant difference at a P value of 0.34, said Dr. Bloch of Tel Aviv (Israel) University.

All patients started 12 consecutive weekly sessions of Malan-based brief focused dynamic psychotherapy by expert psychotherapists, Dr. Bloch said in an interview. At the same time, the women were randomized to receive 50 mg sertraline or a placebo pill for 4 weeks, after which the psychiatrist could choose to increase the dose to 100 mg. After 8 weeks, the drug groups were unblinded and patients could continue open-label drug therapy for 4 weeks if desired.

Two women in the sertraline group developed hypomanic symptoms, but treatment was otherwise well tolerated. Initially, 42 women were enrolled but 2 dropped out during the first week and were not included in the intent-to-treat analysis.

Adding sertraline does not seem to add any benefit to psychotherapy alone, based on this small trial. "While a type 2 error cannot be ruled out, any difference between the groups does not appear to be of clinical significance," Dr. Bloch said.

Prior to this study, Dr. Bloch could find only four randomized and two placebo-controlled studies in the medical literature on antidepressant therapy for postpartum depression. Data comparing pharmacotherapy and psychotherapy for postpartum depression are "virtually lacking," as are studies of the potential efficacy of combining these treatment modalities, he said.

There was no placebo-only comparison in the current study, because it was considered unethical not to offer treatment to women with postpartum depression. Because of this, the investigators could not say that psychotherapy was better than placebo, but the results do suggest that adding sertraline to psychotherapy does not improve upon any effects that psychotherapy might have.

Dr. Bloch said he has no relevant conflicts of interest.

PARIS – Postpartum depression is such a common problem that it’s surprising there are so few randomized, controlled studies comparing drug therapy versus nondrug treatment options. Many women with postpartum depression don’t seek treatment, some are treated only with psychotherapy because of concerns regarding pharmacotherapy, and others are treated with antidepressants alone.

Israeli investigators conducted a small, randomized, controlled study in 40 women with mild to moderate postpartum depression lasting 6 months or longer. They expected psychotherapy plus the antidepressant sertraline to be more effective than psychotherapy alone, but they were surprised to find no additional benefit from the drug.

Response rates were 70% in women who received both psychotherapy and sertraline and 55% in those who got psychotherapy and a placebo. This was not a statistically significant difference at a P value of 0.33, Dr. Miki Bloch and his associates reported at the annual congress of the European College of Neuropsychopharmacology. The rates of remission after 8 weeks of treatment were 65% in the combination therapy group and 50% in the psychotherapy plus placebo group, which also was not a significant difference at a P value of 0.34, said Dr. Bloch of Tel Aviv (Israel) University.

All patients started 12 consecutive weekly sessions of Malan-based brief focused dynamic psychotherapy by expert psychotherapists, Dr. Bloch said in an interview. At the same time, the women were randomized to receive 50 mg sertraline or a placebo pill for 4 weeks, after which the psychiatrist could choose to increase the dose to 100 mg. After 8 weeks, the drug groups were unblinded and patients could continue open-label drug therapy for 4 weeks if desired.

Two women in the sertraline group developed hypomanic symptoms, but treatment was otherwise well tolerated. Initially, 42 women were enrolled but 2 dropped out during the first week and were not included in the intent-to-treat analysis.

Adding sertraline does not seem to add any benefit to psychotherapy alone, based on this small trial. "While a type 2 error cannot be ruled out, any difference between the groups does not appear to be of clinical significance," Dr. Bloch said.

Prior to this study, Dr. Bloch could find only four randomized and two placebo-controlled studies in the medical literature on antidepressant therapy for postpartum depression. Data comparing pharmacotherapy and psychotherapy for postpartum depression are "virtually lacking," as are studies of the potential efficacy of combining these treatment modalities, he said.

There was no placebo-only comparison in the current study, because it was considered unethical not to offer treatment to women with postpartum depression. Because of this, the investigators could not say that psychotherapy was better than placebo, but the results do suggest that adding sertraline to psychotherapy does not improve upon any effects that psychotherapy might have.

Dr. Bloch said he has no relevant conflicts of interest.

PARIS – Postpartum depression is such a common problem that it’s surprising there are so few randomized, controlled studies comparing drug therapy versus nondrug treatment options. Many women with postpartum depression don’t seek treatment, some are treated only with psychotherapy because of concerns regarding pharmacotherapy, and others are treated with antidepressants alone.

Israeli investigators conducted a small, randomized, controlled study in 40 women with mild to moderate postpartum depression lasting 6 months or longer. They expected psychotherapy plus the antidepressant sertraline to be more effective than psychotherapy alone, but they were surprised to find no additional benefit from the drug.

Response rates were 70% in women who received both psychotherapy and sertraline and 55% in those who got psychotherapy and a placebo. This was not a statistically significant difference at a P value of 0.33, Dr. Miki Bloch and his associates reported at the annual congress of the European College of Neuropsychopharmacology. The rates of remission after 8 weeks of treatment were 65% in the combination therapy group and 50% in the psychotherapy plus placebo group, which also was not a significant difference at a P value of 0.34, said Dr. Bloch of Tel Aviv (Israel) University.

All patients started 12 consecutive weekly sessions of Malan-based brief focused dynamic psychotherapy by expert psychotherapists, Dr. Bloch said in an interview. At the same time, the women were randomized to receive 50 mg sertraline or a placebo pill for 4 weeks, after which the psychiatrist could choose to increase the dose to 100 mg. After 8 weeks, the drug groups were unblinded and patients could continue open-label drug therapy for 4 weeks if desired.

Two women in the sertraline group developed hypomanic symptoms, but treatment was otherwise well tolerated. Initially, 42 women were enrolled but 2 dropped out during the first week and were not included in the intent-to-treat analysis.

Adding sertraline does not seem to add any benefit to psychotherapy alone, based on this small trial. "While a type 2 error cannot be ruled out, any difference between the groups does not appear to be of clinical significance," Dr. Bloch said.

Prior to this study, Dr. Bloch could find only four randomized and two placebo-controlled studies in the medical literature on antidepressant therapy for postpartum depression. Data comparing pharmacotherapy and psychotherapy for postpartum depression are "virtually lacking," as are studies of the potential efficacy of combining these treatment modalities, he said.

There was no placebo-only comparison in the current study, because it was considered unethical not to offer treatment to women with postpartum depression. Because of this, the investigators could not say that psychotherapy was better than placebo, but the results do suggest that adding sertraline to psychotherapy does not improve upon any effects that psychotherapy might have.

Dr. Bloch said he has no relevant conflicts of interest.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

SAN FRANCISCO – Evidence continues to mount that thiazolidinediones decrease bone density and increase fracture risk in patients with diabetes, but so far there are no randomized studies to show that adding an antiresorptive drug would protect bone health in this setting, Dr. Jonathan Graf said at the meeting, sponsored by the University of California, San Francisco.

Bisphosphonates, denosumab, and parathyroid hormone have not been tested in human studies to see if they could reduce fracture risk in patients with diabetes who are taking thiazolidinediones, but randomized studies in mice suggest significant bone benefits from adding a bisphosphonate, he said.

For now, however, recommendations call for avoiding thiazolidinediones in patients with diabetes who have a high risk of fracture. A patient's risk should be assessed by using the online FRAX tool and assessing the history for other risk factors for fracture that are not covered by FRAX, said Dr. Graf, a rheumatologist at San Francisco General Hospital.

If you do decide to use a thiazolidinedione to treat diabetes in someone at high risk for fracture, the detrimental effects on bone might be mitigated by using a lower dose. At least two thiazolidinediones – rosiglitazone and pioglitazone – are available in lower-dose formulations in combination with metformin, and the combinations provide the same level of diabetes control as higher-dose glitazone monotherapy, he said.

Preliminary data also suggest that combining lower doses of thiazolidinediones with an incretin drug may provide diabetes control while mitigating adverse effects on bone, he added.

In a prospective cohort study of 84,339 men and women with diabetes, the risk of fracture was 28% higher in patients on thiazolidinediones than in patients taking sulfonylureas, and the risk increased with cumulative exposure to thiazolidinediones. In men, pioglitazone increased fracture risk but rosiglitazone did not (Arch. Intern. Med. 2009;169: 1395-402).

A separate cohort study of 20,964 Medicare beneficiaries over age 65 with diabetes found a statistical trend toward higher risk of peripheral fractures in men and women on thiazolidinedione monotherapy compared with treatment with sulfonylureas or metformin (J. Clin. Endocrinol. Metab. 2009;94:2792-8).

Previous trials have suggested that the fracture risk is higher in women than in men. A meta-analysis of 10 trials and 2 observational studies containing a total of 45,484 patients with diabetes reported a doubling of fracture risk in women but not in men on thiazolidinediones, compared with controls (Can. Med. Assoc. J. 2009;180:32-9).

Thiazolidinedione therapy and the duration of therapy in older patients were associated with significant increases in nonvertebral fractures, including more than a fourfold increased risk of hip or femur fracture, an observational study found (Arch. Intern. Med. 2008;168:820-5).

Compared with that for other diabetes treatments, the 4-year fracture rate in patients on rosiglitazone doubled in both pre- and postmenopausal women but not in men in A Diabetes Outcome Progression Trial (ADOPT), a randomized, double-blind study of about 3,600 patients. The fracture rate was 15% on rosiglitazone, 8% on glyburide, and 7% on metformin (Diab. Care 2008;31:845-51).

Dr. Graf said he has no relevant financial disclosures.

The detrimental effects on bone in diabetic patients might be mitigated by using a thiazolidinedione at a lower dose.

Source DR. GRAF

SAN FRANCISCO – Evidence continues to mount that thiazolidinediones decrease bone density and increase fracture risk in patients with diabetes, but so far there are no randomized studies to show that adding an antiresorptive drug would protect bone health in this setting, Dr. Jonathan Graf said at the meeting, sponsored by the University of California, San Francisco.

Bisphosphonates, denosumab, and parathyroid hormone have not been tested in human studies to see if they could reduce fracture risk in patients with diabetes who are taking thiazolidinediones, but randomized studies in mice suggest significant bone benefits from adding a bisphosphonate, he said.

For now, however, recommendations call for avoiding thiazolidinediones in patients with diabetes who have a high risk of fracture. A patient's risk should be assessed by using the online FRAX tool and assessing the history for other risk factors for fracture that are not covered by FRAX, said Dr. Graf, a rheumatologist at San Francisco General Hospital.

If you do decide to use a thiazolidinedione to treat diabetes in someone at high risk for fracture, the detrimental effects on bone might be mitigated by using a lower dose. At least two thiazolidinediones – rosiglitazone and pioglitazone – are available in lower-dose formulations in combination with metformin, and the combinations provide the same level of diabetes control as higher-dose glitazone monotherapy, he said.

Preliminary data also suggest that combining lower doses of thiazolidinediones with an incretin drug may provide diabetes control while mitigating adverse effects on bone, he added.

In a prospective cohort study of 84,339 men and women with diabetes, the risk of fracture was 28% higher in patients on thiazolidinediones than in patients taking sulfonylureas, and the risk increased with cumulative exposure to thiazolidinediones. In men, pioglitazone increased fracture risk but rosiglitazone did not (Arch. Intern. Med. 2009;169: 1395-402).

A separate cohort study of 20,964 Medicare beneficiaries over age 65 with diabetes found a statistical trend toward higher risk of peripheral fractures in men and women on thiazolidinedione monotherapy compared with treatment with sulfonylureas or metformin (J. Clin. Endocrinol. Metab. 2009;94:2792-8).

Previous trials have suggested that the fracture risk is higher in women than in men. A meta-analysis of 10 trials and 2 observational studies containing a total of 45,484 patients with diabetes reported a doubling of fracture risk in women but not in men on thiazolidinediones, compared with controls (Can. Med. Assoc. J. 2009;180:32-9).

Thiazolidinedione therapy and the duration of therapy in older patients were associated with significant increases in nonvertebral fractures, including more than a fourfold increased risk of hip or femur fracture, an observational study found (Arch. Intern. Med. 2008;168:820-5).

Compared with that for other diabetes treatments, the 4-year fracture rate in patients on rosiglitazone doubled in both pre- and postmenopausal women but not in men in A Diabetes Outcome Progression Trial (ADOPT), a randomized, double-blind study of about 3,600 patients. The fracture rate was 15% on rosiglitazone, 8% on glyburide, and 7% on metformin (Diab. Care 2008;31:845-51).

Dr. Graf said he has no relevant financial disclosures.

The detrimental effects on bone in diabetic patients might be mitigated by using a thiazolidinedione at a lower dose.

Source DR. GRAF

SAN FRANCISCO – Evidence continues to mount that thiazolidinediones decrease bone density and increase fracture risk in patients with diabetes, but so far there are no randomized studies to show that adding an antiresorptive drug would protect bone health in this setting, Dr. Jonathan Graf said at the meeting, sponsored by the University of California, San Francisco.

Bisphosphonates, denosumab, and parathyroid hormone have not been tested in human studies to see if they could reduce fracture risk in patients with diabetes who are taking thiazolidinediones, but randomized studies in mice suggest significant bone benefits from adding a bisphosphonate, he said.

For now, however, recommendations call for avoiding thiazolidinediones in patients with diabetes who have a high risk of fracture. A patient's risk should be assessed by using the online FRAX tool and assessing the history for other risk factors for fracture that are not covered by FRAX, said Dr. Graf, a rheumatologist at San Francisco General Hospital.

If you do decide to use a thiazolidinedione to treat diabetes in someone at high risk for fracture, the detrimental effects on bone might be mitigated by using a lower dose. At least two thiazolidinediones – rosiglitazone and pioglitazone – are available in lower-dose formulations in combination with metformin, and the combinations provide the same level of diabetes control as higher-dose glitazone monotherapy, he said.

Preliminary data also suggest that combining lower doses of thiazolidinediones with an incretin drug may provide diabetes control while mitigating adverse effects on bone, he added.

In a prospective cohort study of 84,339 men and women with diabetes, the risk of fracture was 28% higher in patients on thiazolidinediones than in patients taking sulfonylureas, and the risk increased with cumulative exposure to thiazolidinediones. In men, pioglitazone increased fracture risk but rosiglitazone did not (Arch. Intern. Med. 2009;169: 1395-402).

A separate cohort study of 20,964 Medicare beneficiaries over age 65 with diabetes found a statistical trend toward higher risk of peripheral fractures in men and women on thiazolidinedione monotherapy compared with treatment with sulfonylureas or metformin (J. Clin. Endocrinol. Metab. 2009;94:2792-8).

Previous trials have suggested that the fracture risk is higher in women than in men. A meta-analysis of 10 trials and 2 observational studies containing a total of 45,484 patients with diabetes reported a doubling of fracture risk in women but not in men on thiazolidinediones, compared with controls (Can. Med. Assoc. J. 2009;180:32-9).

Thiazolidinedione therapy and the duration of therapy in older patients were associated with significant increases in nonvertebral fractures, including more than a fourfold increased risk of hip or femur fracture, an observational study found (Arch. Intern. Med. 2008;168:820-5).

Compared with that for other diabetes treatments, the 4-year fracture rate in patients on rosiglitazone doubled in both pre- and postmenopausal women but not in men in A Diabetes Outcome Progression Trial (ADOPT), a randomized, double-blind study of about 3,600 patients. The fracture rate was 15% on rosiglitazone, 8% on glyburide, and 7% on metformin (Diab. Care 2008;31:845-51).

Dr. Graf said he has no relevant financial disclosures.

The detrimental effects on bone in diabetic patients might be mitigated by using a thiazolidinedione at a lower dose.

Source DR. GRAF

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed only loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

There's a lot of controversy surrounding the Institute of Medicine's (IOM) November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” which updated 1997 guidelines.

Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her individual patients. And as a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a conference on osteoporosis sponsored by the University of California, San Francisco.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

Many experts, however, think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30- to 32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients to get 1,200 IU/day of vitamin D.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815-22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels.

The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629-37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30- to 40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day if they are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day at older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200-1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses of calcium.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction or vascular calcification (Circulation 2007; 115:846-54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262-6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19: 342:d2040). There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted.

“Whether this truly represents an increased risk or not is unclear,” Dr. Sellmeyer said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added.

The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010; 341:c3691).

“It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said.

“I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Calcium citrate probably is a little better absorbed than calcium carbonate and may be a little less constipating, “but for a lot of people it doesn't matter,” she said.

As always, physicians should be alert for conditions in their patients that might warrant higher intakes of calcium or vitamin D, she said, including malabsorption (as in patients who underwent gastric bypass surgery), healing osteomalacia, fracture healing, anabolic therapy, postoperative hyperparathyroidism, hypoparathyroidism, or adolescence.

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU per day of vitamin D to reach 'sufficient' serum levels of 30-32 ng/mL.

Source DR. SELLMEYER

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed only loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

There's a lot of controversy surrounding the Institute of Medicine's (IOM) November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” which updated 1997 guidelines.

Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her individual patients. And as a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a conference on osteoporosis sponsored by the University of California, San Francisco.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

Many experts, however, think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30- to 32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients to get 1,200 IU/day of vitamin D.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815-22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels.

The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629-37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30- to 40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day if they are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day at older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200-1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses of calcium.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction or vascular calcification (Circulation 2007; 115:846-54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262-6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19: 342:d2040). There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted.

“Whether this truly represents an increased risk or not is unclear,” Dr. Sellmeyer said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added.

The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010; 341:c3691).

“It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said.

“I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Calcium citrate probably is a little better absorbed than calcium carbonate and may be a little less constipating, “but for a lot of people it doesn't matter,” she said.

As always, physicians should be alert for conditions in their patients that might warrant higher intakes of calcium or vitamin D, she said, including malabsorption (as in patients who underwent gastric bypass surgery), healing osteomalacia, fracture healing, anabolic therapy, postoperative hyperparathyroidism, hypoparathyroidism, or adolescence.

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU per day of vitamin D to reach 'sufficient' serum levels of 30-32 ng/mL.

Source DR. SELLMEYER

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed only loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

There's a lot of controversy surrounding the Institute of Medicine's (IOM) November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” which updated 1997 guidelines.

Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her individual patients. And as a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a conference on osteoporosis sponsored by the University of California, San Francisco.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

Many experts, however, think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30- to 32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients to get 1,200 IU/day of vitamin D.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815-22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels.

The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629-37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30- to 40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day if they are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day at older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200-1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses of calcium.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction or vascular calcification (Circulation 2007; 115:846-54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262-6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19: 342:d2040). There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted.

“Whether this truly represents an increased risk or not is unclear,” Dr. Sellmeyer said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added.

The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010; 341:c3691).

“It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said.

“I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Calcium citrate probably is a little better absorbed than calcium carbonate and may be a little less constipating, “but for a lot of people it doesn't matter,” she said.

As always, physicians should be alert for conditions in their patients that might warrant higher intakes of calcium or vitamin D, she said, including malabsorption (as in patients who underwent gastric bypass surgery), healing osteomalacia, fracture healing, anabolic therapy, postoperative hyperparathyroidism, hypoparathyroidism, or adolescence.

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU per day of vitamin D to reach 'sufficient' serum levels of 30-32 ng/mL.

Source DR. SELLMEYER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and does not necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting, sponsored by the university.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, then he said he considers ordering follow-up bone mineral density testing. “There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842-8).

Then there's the “regression to the mean” argument that patients with an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained a mean of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318-21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation.

Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements. The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296-304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117-1123). In general, approximately 30%-40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and does not necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting, sponsored by the university.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, then he said he considers ordering follow-up bone mineral density testing. “There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842-8).

Then there's the “regression to the mean” argument that patients with an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained a mean of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318-21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation.

Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements. The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296-304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117-1123). In general, approximately 30%-40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and does not necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting, sponsored by the university.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, then he said he considers ordering follow-up bone mineral density testing. “There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842-8).

Then there's the “regression to the mean” argument that patients with an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained a mean of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318-21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation.

Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements. The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296-304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117-1123). In general, approximately 30%-40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER