Patrice Wendling

CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

CHICAGO — Clearance of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream was sustained in a high proportion of patients during 5 years of an open-label study.

The initial clinical clearance rate in the European study was about 90% (163 of 182 patients) 12 weeks after treatment with once-daily imiquimod 5% cream (Aldara) five times a week for 6 weeks.

The sustained clearance rate among 162 patients who initially cleared was estimated at 87% at 5 years of follow-up, Dr. Harald Gollnick and associates reported in a poster at the Academy of Dermatology's Academy 2008 meeting. (One patient who cleared at the 12-week visit died prior to entering follow-up.) The estimated probability of treatment success at the end of year 5 was 78% among all 182 patients.

The proportion of patients who were clinically clear at 2 years was estimated to be 79%, according to previously published results (Eur. J. Dermatol. 2005;15:374-81).

The study, funded by 3M Pharmaceuticals and Meda Pharmaceuticals, included patients (mean age 65 years) with a primary, biopsy-confirmed tumor at least 0.5 cm

Overall, 18 patients had a clinical recurrence of the target lesion, with most recurrences (14) occurring during the first 2 years of follow-up. Fourteen recurrences (78%) were confirmed on biopsy, according to the investigators, who have been consultants to, and received honoraria from, Meda.

In all, 36 patients had 74 serious adverse events, all of which were considered probably not related to imiquimod. Most local skin reactions resolved by 3 months, but in some patients, erythema took several years to resolve, reported Dr. Gollnick of Otto von Guericke University of Magdeburg (Germany) and associates.

CHICAGO — Clearance of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream was sustained in a high proportion of patients during 5 years of an open-label study.

The initial clinical clearance rate in the European study was about 90% (163 of 182 patients) 12 weeks after treatment with once-daily imiquimod 5% cream (Aldara) five times a week for 6 weeks.

The sustained clearance rate among 162 patients who initially cleared was estimated at 87% at 5 years of follow-up, Dr. Harald Gollnick and associates reported in a poster at the Academy of Dermatology's Academy 2008 meeting. (One patient who cleared at the 12-week visit died prior to entering follow-up.) The estimated probability of treatment success at the end of year 5 was 78% among all 182 patients.

The proportion of patients who were clinically clear at 2 years was estimated to be 79%, according to previously published results (Eur. J. Dermatol. 2005;15:374-81).

The study, funded by 3M Pharmaceuticals and Meda Pharmaceuticals, included patients (mean age 65 years) with a primary, biopsy-confirmed tumor at least 0.5 cm

Overall, 18 patients had a clinical recurrence of the target lesion, with most recurrences (14) occurring during the first 2 years of follow-up. Fourteen recurrences (78%) were confirmed on biopsy, according to the investigators, who have been consultants to, and received honoraria from, Meda.

In all, 36 patients had 74 serious adverse events, all of which were considered probably not related to imiquimod. Most local skin reactions resolved by 3 months, but in some patients, erythema took several years to resolve, reported Dr. Gollnick of Otto von Guericke University of Magdeburg (Germany) and associates.

CHICAGO — Clearance of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream was sustained in a high proportion of patients during 5 years of an open-label study.

The initial clinical clearance rate in the European study was about 90% (163 of 182 patients) 12 weeks after treatment with once-daily imiquimod 5% cream (Aldara) five times a week for 6 weeks.

The sustained clearance rate among 162 patients who initially cleared was estimated at 87% at 5 years of follow-up, Dr. Harald Gollnick and associates reported in a poster at the Academy of Dermatology's Academy 2008 meeting. (One patient who cleared at the 12-week visit died prior to entering follow-up.) The estimated probability of treatment success at the end of year 5 was 78% among all 182 patients.

The proportion of patients who were clinically clear at 2 years was estimated to be 79%, according to previously published results (Eur. J. Dermatol. 2005;15:374-81).

The study, funded by 3M Pharmaceuticals and Meda Pharmaceuticals, included patients (mean age 65 years) with a primary, biopsy-confirmed tumor at least 0.5 cm

Overall, 18 patients had a clinical recurrence of the target lesion, with most recurrences (14) occurring during the first 2 years of follow-up. Fourteen recurrences (78%) were confirmed on biopsy, according to the investigators, who have been consultants to, and received honoraria from, Meda.

In all, 36 patients had 74 serious adverse events, all of which were considered probably not related to imiquimod. Most local skin reactions resolved by 3 months, but in some patients, erythema took several years to resolve, reported Dr. Gollnick of Otto von Guericke University of Magdeburg (Germany) and associates.

CHICAGO – The investigational agent pimavanserin appears to lessen the symptoms of psychosis in patients with Parkinson's disease without worsening motor function, according to data from a multicenter randomized phase II trial involving 60 patients.

Pimavanserin is a potent, active 5-hydroxytryptamine 2a (5-HT_2a) serotonin receptor antagonist, according to Dr. Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D₂) and histamine receptor (H₁) binding that are linked to intolerable adverse effects of other antipsychotics. Pimavanserin is being developed as a cotherapy for schizophrenia, as well as for Parkinson's disease psychosis.

Patients in the study had Parkinson's disease and psychosis and received either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Patients treated with pimavanserin demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, as compared with an 11% improvement for patients treated with placebo, Dr. Stephen Revell and associates reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were observed for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in absolute mean change from baseline to day 28 in UPDRS motor scores (−3.05 vs. −1.24) or activities of daily living scores (−2.51 vs. −0.70).

No differences were observed between groups on the Schwab and England Activities of Daily Living Scale part of the UPDRS or the Clinical Global Impression Scale severity of illness subscale.

The most common adverse events in patients treated with pimavanserin were somnolence, edema, and increased blood urea–each occurring in three patients, the authors wrote.

In a second poster presented at the meeting, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72 years) with Parkinson's and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Adverse events commonly experienced with clozapine and quetiapine–such as somnolence, fatigue, and dizziness–were uncommon with pimavanserin, according to Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

Only one patient who experienced somnolence discontinued pimavanserin treatment. A single case of rhabdomyolysis was the only serious adverse event considered to be possibly treatment-related.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – The investigational agent pimavanserin appears to lessen the symptoms of psychosis in patients with Parkinson's disease without worsening motor function, according to data from a multicenter randomized phase II trial involving 60 patients.

Pimavanserin is a potent, active 5-hydroxytryptamine 2a (5-HT_2a) serotonin receptor antagonist, according to Dr. Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D₂) and histamine receptor (H₁) binding that are linked to intolerable adverse effects of other antipsychotics. Pimavanserin is being developed as a cotherapy for schizophrenia, as well as for Parkinson's disease psychosis.

Patients in the study had Parkinson's disease and psychosis and received either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Patients treated with pimavanserin demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, as compared with an 11% improvement for patients treated with placebo, Dr. Stephen Revell and associates reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were observed for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in absolute mean change from baseline to day 28 in UPDRS motor scores (−3.05 vs. −1.24) or activities of daily living scores (−2.51 vs. −0.70).

No differences were observed between groups on the Schwab and England Activities of Daily Living Scale part of the UPDRS or the Clinical Global Impression Scale severity of illness subscale.

The most common adverse events in patients treated with pimavanserin were somnolence, edema, and increased blood urea–each occurring in three patients, the authors wrote.

In a second poster presented at the meeting, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72 years) with Parkinson's and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Adverse events commonly experienced with clozapine and quetiapine–such as somnolence, fatigue, and dizziness–were uncommon with pimavanserin, according to Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

Only one patient who experienced somnolence discontinued pimavanserin treatment. A single case of rhabdomyolysis was the only serious adverse event considered to be possibly treatment-related.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – The investigational agent pimavanserin appears to lessen the symptoms of psychosis in patients with Parkinson's disease without worsening motor function, according to data from a multicenter randomized phase II trial involving 60 patients.

Pimavanserin is a potent, active 5-hydroxytryptamine 2a (5-HT_2a) serotonin receptor antagonist, according to Dr. Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D₂) and histamine receptor (H₁) binding that are linked to intolerable adverse effects of other antipsychotics. Pimavanserin is being developed as a cotherapy for schizophrenia, as well as for Parkinson's disease psychosis.

Patients in the study had Parkinson's disease and psychosis and received either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Patients treated with pimavanserin demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, as compared with an 11% improvement for patients treated with placebo, Dr. Stephen Revell and associates reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were observed for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in absolute mean change from baseline to day 28 in UPDRS motor scores (−3.05 vs. −1.24) or activities of daily living scores (−2.51 vs. −0.70).

No differences were observed between groups on the Schwab and England Activities of Daily Living Scale part of the UPDRS or the Clinical Global Impression Scale severity of illness subscale.

The most common adverse events in patients treated with pimavanserin were somnolence, edema, and increased blood urea–each occurring in three patients, the authors wrote.

In a second poster presented at the meeting, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72 years) with Parkinson's and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Adverse events commonly experienced with clozapine and quetiapine–such as somnolence, fatigue, and dizziness–were uncommon with pimavanserin, according to Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

Only one patient who experienced somnolence discontinued pimavanserin treatment. A single case of rhabdomyolysis was the only serious adverse event considered to be possibly treatment-related.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – The antidepressant milnacipran appears to provide sustained pain relief in patients with fibromyalgia.

In a 28-week, randomized blinded extension trial in 449 patients with fibromyalgia, durable pain relief and improved overall well-being was reported after 1 year of use by patients who responded to milnacipran during the trial's lead-in phase, lead investigator Dr. Don Goldenberg and associates reported in a poster at the annual meeting of the American Academy of Neurology. No new safety concerns emerged.

“Milnacipran is safe and effective for long-term use in fibromyalgia patients,” concluded Dr. Goldenberg of Massachusetts General Hospital in Boston, who disclosed receiving personal consulting fees from Forest Laboratories, one of the companies–along with Cypress Bioscience Inc.–that sponsored this trial.

Milnacipran is a dual-reuptake inhibitor that is unique in that it raises levels of the neurotransmitter norepinephrine more than serotonin.

Marketed as Ixel for depression in Europe and Asia for years, milnacipran is not approved for any use in the United States. Despite its lack of Food and Drug Administration approval, word about milnacipran has spread on fibromyalgia patient Web sites.

A new drug application for milnacipran as a fibromyalgia treatment was filed with the FDA in December 2007 by Forest Laboratories Inc. and Cypress Bioscience Inc.

Patients enrolled in the trial had successfully completed a 6-month lead-in trial and were maintained on milnacipran 200 mg/day or rerandomized from placebo or milnacipran 100 mg/day to either milnacipran 100 mg/day or 200 mg/day for an additional 6 months of treatment. Their mean age was 50 years, more than 95% were female, and the mean duration of fibromyalgia was about 5.5 years.

Efficacy was measured as mean change from lead-in baseline to week 55 in pain recall scores, in Patient Global Impression of Change (PGIC) Scale scores, and in total Fibromyalgia Impact Questionnaire (FIQ) scores. No statistical analyses were performed to determine significance for the efficacy outcomes. This is noteworthy, as a pivotal phase III trial in 888 patients with fibromyalgia reported in September 2005 that its primary efficacy assessments failed to demonstrate statistical significance.

The current analyses were based on 147 of 209 patients maintained on milnacipran 200 mg/day for both phases of the study; 63 of 92 patients switched from milnacipran 100 mg/day to 200 mg/day; and 65 of 100 patients who switched from placebo to milnacipran 200 mg/day.

Efficacy data were not available on the 48 patients receiving milnacipran 100 mg in the extension phase.

Patients continuing on milnacipran 200 mg/day in the extension study showed a 46% improvement in mean pain recall scores, the investigators reported.

Patients switched from milnacipran 100 mg/day to 200 mg/day maintained the pain relief achieved in the lead-in trial and showed an additional 12% reduction in pain scores at the higher dose. Overall, their mean pain scores improved 52% from lead-in baseline.

Mean scores on the 7-point PGIC scale were 2.18 for patients continuing on milnacipran 200 mg/day and 1.91 for patients switching from 100 mg/day to 200 mg/day, indicating improvements in both groups after 1 year, according to the investigators. A score of 1 equals “very much improved” and 2 equals “much improved.”

At week 55, the improvement in total FIQ scores was 49% among patients who switched from 100 mg/day to 200 mg/day and 41.5% among those maintained on 200 mg.

Patients switched from placebo to milnacipran 200 mg in the extension trial experienced a 47% improvement in their mean pain total scores after 28 weeks of treatment.

Similar improvements were observed in PGIC and FIQ, according to Dr. Goldenberg, who disclosed that along with fees from Forest Laboratories, he has received personal consulting fees from Eli Lilly & Co. and Merck & Co.

The drug was well tolerated at doses of 100 mg/day and 200 mg/day, and the majority of adverse events were mild to moderate. Data on serious adverse events were not presented in the poster and were not available from the investigators at press time.

The most common newly emergent adverse event during the extension phase in patients continuing on milnacipran was nausea, which was reported in 13% of these patients.

CHICAGO – The antidepressant milnacipran appears to provide sustained pain relief in patients with fibromyalgia.

In a 28-week, randomized blinded extension trial in 449 patients with fibromyalgia, durable pain relief and improved overall well-being was reported after 1 year of use by patients who responded to milnacipran during the trial's lead-in phase, lead investigator Dr. Don Goldenberg and associates reported in a poster at the annual meeting of the American Academy of Neurology. No new safety concerns emerged.

“Milnacipran is safe and effective for long-term use in fibromyalgia patients,” concluded Dr. Goldenberg of Massachusetts General Hospital in Boston, who disclosed receiving personal consulting fees from Forest Laboratories, one of the companies–along with Cypress Bioscience Inc.–that sponsored this trial.

Milnacipran is a dual-reuptake inhibitor that is unique in that it raises levels of the neurotransmitter norepinephrine more than serotonin.

Marketed as Ixel for depression in Europe and Asia for years, milnacipran is not approved for any use in the United States. Despite its lack of Food and Drug Administration approval, word about milnacipran has spread on fibromyalgia patient Web sites.

A new drug application for milnacipran as a fibromyalgia treatment was filed with the FDA in December 2007 by Forest Laboratories Inc. and Cypress Bioscience Inc.

Patients enrolled in the trial had successfully completed a 6-month lead-in trial and were maintained on milnacipran 200 mg/day or rerandomized from placebo or milnacipran 100 mg/day to either milnacipran 100 mg/day or 200 mg/day for an additional 6 months of treatment. Their mean age was 50 years, more than 95% were female, and the mean duration of fibromyalgia was about 5.5 years.

Efficacy was measured as mean change from lead-in baseline to week 55 in pain recall scores, in Patient Global Impression of Change (PGIC) Scale scores, and in total Fibromyalgia Impact Questionnaire (FIQ) scores. No statistical analyses were performed to determine significance for the efficacy outcomes. This is noteworthy, as a pivotal phase III trial in 888 patients with fibromyalgia reported in September 2005 that its primary efficacy assessments failed to demonstrate statistical significance.

The current analyses were based on 147 of 209 patients maintained on milnacipran 200 mg/day for both phases of the study; 63 of 92 patients switched from milnacipran 100 mg/day to 200 mg/day; and 65 of 100 patients who switched from placebo to milnacipran 200 mg/day.

Efficacy data were not available on the 48 patients receiving milnacipran 100 mg in the extension phase.

Patients continuing on milnacipran 200 mg/day in the extension study showed a 46% improvement in mean pain recall scores, the investigators reported.

Patients switched from milnacipran 100 mg/day to 200 mg/day maintained the pain relief achieved in the lead-in trial and showed an additional 12% reduction in pain scores at the higher dose. Overall, their mean pain scores improved 52% from lead-in baseline.

Mean scores on the 7-point PGIC scale were 2.18 for patients continuing on milnacipran 200 mg/day and 1.91 for patients switching from 100 mg/day to 200 mg/day, indicating improvements in both groups after 1 year, according to the investigators. A score of 1 equals “very much improved” and 2 equals “much improved.”

At week 55, the improvement in total FIQ scores was 49% among patients who switched from 100 mg/day to 200 mg/day and 41.5% among those maintained on 200 mg.

Patients switched from placebo to milnacipran 200 mg in the extension trial experienced a 47% improvement in their mean pain total scores after 28 weeks of treatment.

Similar improvements were observed in PGIC and FIQ, according to Dr. Goldenberg, who disclosed that along with fees from Forest Laboratories, he has received personal consulting fees from Eli Lilly & Co. and Merck & Co.

The drug was well tolerated at doses of 100 mg/day and 200 mg/day, and the majority of adverse events were mild to moderate. Data on serious adverse events were not presented in the poster and were not available from the investigators at press time.

The most common newly emergent adverse event during the extension phase in patients continuing on milnacipran was nausea, which was reported in 13% of these patients.

CHICAGO – The antidepressant milnacipran appears to provide sustained pain relief in patients with fibromyalgia.

In a 28-week, randomized blinded extension trial in 449 patients with fibromyalgia, durable pain relief and improved overall well-being was reported after 1 year of use by patients who responded to milnacipran during the trial's lead-in phase, lead investigator Dr. Don Goldenberg and associates reported in a poster at the annual meeting of the American Academy of Neurology. No new safety concerns emerged.

“Milnacipran is safe and effective for long-term use in fibromyalgia patients,” concluded Dr. Goldenberg of Massachusetts General Hospital in Boston, who disclosed receiving personal consulting fees from Forest Laboratories, one of the companies–along with Cypress Bioscience Inc.–that sponsored this trial.

Milnacipran is a dual-reuptake inhibitor that is unique in that it raises levels of the neurotransmitter norepinephrine more than serotonin.

Marketed as Ixel for depression in Europe and Asia for years, milnacipran is not approved for any use in the United States. Despite its lack of Food and Drug Administration approval, word about milnacipran has spread on fibromyalgia patient Web sites.

A new drug application for milnacipran as a fibromyalgia treatment was filed with the FDA in December 2007 by Forest Laboratories Inc. and Cypress Bioscience Inc.

Patients enrolled in the trial had successfully completed a 6-month lead-in trial and were maintained on milnacipran 200 mg/day or rerandomized from placebo or milnacipran 100 mg/day to either milnacipran 100 mg/day or 200 mg/day for an additional 6 months of treatment. Their mean age was 50 years, more than 95% were female, and the mean duration of fibromyalgia was about 5.5 years.

Efficacy was measured as mean change from lead-in baseline to week 55 in pain recall scores, in Patient Global Impression of Change (PGIC) Scale scores, and in total Fibromyalgia Impact Questionnaire (FIQ) scores. No statistical analyses were performed to determine significance for the efficacy outcomes. This is noteworthy, as a pivotal phase III trial in 888 patients with fibromyalgia reported in September 2005 that its primary efficacy assessments failed to demonstrate statistical significance.

The current analyses were based on 147 of 209 patients maintained on milnacipran 200 mg/day for both phases of the study; 63 of 92 patients switched from milnacipran 100 mg/day to 200 mg/day; and 65 of 100 patients who switched from placebo to milnacipran 200 mg/day.

Efficacy data were not available on the 48 patients receiving milnacipran 100 mg in the extension phase.

Patients continuing on milnacipran 200 mg/day in the extension study showed a 46% improvement in mean pain recall scores, the investigators reported.

Patients switched from milnacipran 100 mg/day to 200 mg/day maintained the pain relief achieved in the lead-in trial and showed an additional 12% reduction in pain scores at the higher dose. Overall, their mean pain scores improved 52% from lead-in baseline.

Mean scores on the 7-point PGIC scale were 2.18 for patients continuing on milnacipran 200 mg/day and 1.91 for patients switching from 100 mg/day to 200 mg/day, indicating improvements in both groups after 1 year, according to the investigators. A score of 1 equals “very much improved” and 2 equals “much improved.”

At week 55, the improvement in total FIQ scores was 49% among patients who switched from 100 mg/day to 200 mg/day and 41.5% among those maintained on 200 mg.

Patients switched from placebo to milnacipran 200 mg in the extension trial experienced a 47% improvement in their mean pain total scores after 28 weeks of treatment.

Similar improvements were observed in PGIC and FIQ, according to Dr. Goldenberg, who disclosed that along with fees from Forest Laboratories, he has received personal consulting fees from Eli Lilly & Co. and Merck & Co.

The drug was well tolerated at doses of 100 mg/day and 200 mg/day, and the majority of adverse events were mild to moderate. Data on serious adverse events were not presented in the poster and were not available from the investigators at press time.

The most common newly emergent adverse event during the extension phase in patients continuing on milnacipran was nausea, which was reported in 13% of these patients.

CHICAGO – Deep brain stimulation of limbic relays within the basal ganglia circuitry reduced tic severity in patients with Tourette syndrome, according to data from a small double-blind, randomized crossover study.

In three patients with severe and medically refractory Tourette syndrome, researchers applied high-frequency bilateral deep brain stimulation to two structures that form part of the basal ganglia associative-limbic circuits–the centromedian-parafascicular complex (CM-Pf) of the thalamus and the ventromedial part of the globus pallidus interna (GPi).

Patients and investigators were blinded at evaluation to the four stimulation conditions–thalamic, pallidal, simultaneous thalamic and pallidal, and sham.

The greatest lessening of tics was achieved with ventromedial GPi stimulation, coinvestigator Dr. Luc Mallet said at the 12th International Congress of Parkinson's Disease and Movement Disorders. The total Yale Global Tic Severity Scale (YGTSS) score was reduced 65%, 96%, and 74% from baseline in patients 1, 2, and 3, respectively.

CM-Pf stimulation reduced tic severity by 64%, 30%, and 40%, respectively. Combining thalamic and pallidal stimulation did not improve tic reduction in the study (Arch. Neurol. 2008;65:952-7).

In patient No. 2, the best result was obtained after 1 month with stimulation, but the effects decreased after 2 months, even with increased voltage, said Dr. Mallet of Pitié-Salpêtrière Hospital, Paris.

Very good long-term effects were observed in patient No. 1, who was identified with borderline personality disorder before surgery.

The decrease in tic severity was accompanied by a dramatic reduction in self-injurious behaviors and impulsiveness, allowing the patient to start psychotherapy, to improve autonomy and social relationships, and to return to full-time work 2 years after surgery. Although tics are involuntary movements, they are influenced by emotional context, explained Dr. Mallet, who disclosed no conflicts of interest.

In patient No. 2, a stable reduction in tic severity was achieved 27 months after surgery using 20 hours of pallidal stimulation followed by 4 hours off. In patient 3, tic severity was reduced by 74% at 20 months without medication under pallidal and thalamic stimulation.

No neuropsychological, psychiatric, or other long-term adverse effects were observed.

The findings confirm those of open-label studies and case reports, and support the theory that Tourette results from dysfunction of the associative-limbic territories of the basal ganglia, Dr. Mallet said.

“We need further controlled studies to compare the two targets between the thalamus and the pallidum, but this is very encouraging for a proposed treatment for Tourette,” he said.

There is a large French multicenter study underway to evaluate ventromedial GPi stimulation in patients with Tourette.

Ventromedial GPi stimulation may be more efficient than CM-Pf because the GPi is a key structure for the output nucleus of the main basal ganglia pathway, whereas the CM-Pf is part of an indirect, internal loop of the basal ganglia circuitry, according to the investigators.

The current study was also by Dr. Marie-Laure Welter and was sponsored by the French National Institute for Health and Medical Research, the University of Pierre and Marie Curie in Paris, and the Public Assistance Hospital of Paris.

CHICAGO – Deep brain stimulation of limbic relays within the basal ganglia circuitry reduced tic severity in patients with Tourette syndrome, according to data from a small double-blind, randomized crossover study.

In three patients with severe and medically refractory Tourette syndrome, researchers applied high-frequency bilateral deep brain stimulation to two structures that form part of the basal ganglia associative-limbic circuits–the centromedian-parafascicular complex (CM-Pf) of the thalamus and the ventromedial part of the globus pallidus interna (GPi).

Patients and investigators were blinded at evaluation to the four stimulation conditions–thalamic, pallidal, simultaneous thalamic and pallidal, and sham.

The greatest lessening of tics was achieved with ventromedial GPi stimulation, coinvestigator Dr. Luc Mallet said at the 12th International Congress of Parkinson's Disease and Movement Disorders. The total Yale Global Tic Severity Scale (YGTSS) score was reduced 65%, 96%, and 74% from baseline in patients 1, 2, and 3, respectively.

CM-Pf stimulation reduced tic severity by 64%, 30%, and 40%, respectively. Combining thalamic and pallidal stimulation did not improve tic reduction in the study (Arch. Neurol. 2008;65:952-7).

In patient No. 2, the best result was obtained after 1 month with stimulation, but the effects decreased after 2 months, even with increased voltage, said Dr. Mallet of Pitié-Salpêtrière Hospital, Paris.

Very good long-term effects were observed in patient No. 1, who was identified with borderline personality disorder before surgery.

The decrease in tic severity was accompanied by a dramatic reduction in self-injurious behaviors and impulsiveness, allowing the patient to start psychotherapy, to improve autonomy and social relationships, and to return to full-time work 2 years after surgery. Although tics are involuntary movements, they are influenced by emotional context, explained Dr. Mallet, who disclosed no conflicts of interest.

In patient No. 2, a stable reduction in tic severity was achieved 27 months after surgery using 20 hours of pallidal stimulation followed by 4 hours off. In patient 3, tic severity was reduced by 74% at 20 months without medication under pallidal and thalamic stimulation.

No neuropsychological, psychiatric, or other long-term adverse effects were observed.

The findings confirm those of open-label studies and case reports, and support the theory that Tourette results from dysfunction of the associative-limbic territories of the basal ganglia, Dr. Mallet said.

“We need further controlled studies to compare the two targets between the thalamus and the pallidum, but this is very encouraging for a proposed treatment for Tourette,” he said.

There is a large French multicenter study underway to evaluate ventromedial GPi stimulation in patients with Tourette.

Ventromedial GPi stimulation may be more efficient than CM-Pf because the GPi is a key structure for the output nucleus of the main basal ganglia pathway, whereas the CM-Pf is part of an indirect, internal loop of the basal ganglia circuitry, according to the investigators.

The current study was also by Dr. Marie-Laure Welter and was sponsored by the French National Institute for Health and Medical Research, the University of Pierre and Marie Curie in Paris, and the Public Assistance Hospital of Paris.

CHICAGO – Deep brain stimulation of limbic relays within the basal ganglia circuitry reduced tic severity in patients with Tourette syndrome, according to data from a small double-blind, randomized crossover study.

In three patients with severe and medically refractory Tourette syndrome, researchers applied high-frequency bilateral deep brain stimulation to two structures that form part of the basal ganglia associative-limbic circuits–the centromedian-parafascicular complex (CM-Pf) of the thalamus and the ventromedial part of the globus pallidus interna (GPi).

Patients and investigators were blinded at evaluation to the four stimulation conditions–thalamic, pallidal, simultaneous thalamic and pallidal, and sham.

The greatest lessening of tics was achieved with ventromedial GPi stimulation, coinvestigator Dr. Luc Mallet said at the 12th International Congress of Parkinson's Disease and Movement Disorders. The total Yale Global Tic Severity Scale (YGTSS) score was reduced 65%, 96%, and 74% from baseline in patients 1, 2, and 3, respectively.

CM-Pf stimulation reduced tic severity by 64%, 30%, and 40%, respectively. Combining thalamic and pallidal stimulation did not improve tic reduction in the study (Arch. Neurol. 2008;65:952-7).

In patient No. 2, the best result was obtained after 1 month with stimulation, but the effects decreased after 2 months, even with increased voltage, said Dr. Mallet of Pitié-Salpêtrière Hospital, Paris.

Very good long-term effects were observed in patient No. 1, who was identified with borderline personality disorder before surgery.

The decrease in tic severity was accompanied by a dramatic reduction in self-injurious behaviors and impulsiveness, allowing the patient to start psychotherapy, to improve autonomy and social relationships, and to return to full-time work 2 years after surgery. Although tics are involuntary movements, they are influenced by emotional context, explained Dr. Mallet, who disclosed no conflicts of interest.

In patient No. 2, a stable reduction in tic severity was achieved 27 months after surgery using 20 hours of pallidal stimulation followed by 4 hours off. In patient 3, tic severity was reduced by 74% at 20 months without medication under pallidal and thalamic stimulation.

No neuropsychological, psychiatric, or other long-term adverse effects were observed.

The findings confirm those of open-label studies and case reports, and support the theory that Tourette results from dysfunction of the associative-limbic territories of the basal ganglia, Dr. Mallet said.

“We need further controlled studies to compare the two targets between the thalamus and the pallidum, but this is very encouraging for a proposed treatment for Tourette,” he said.

There is a large French multicenter study underway to evaluate ventromedial GPi stimulation in patients with Tourette.

Ventromedial GPi stimulation may be more efficient than CM-Pf because the GPi is a key structure for the output nucleus of the main basal ganglia pathway, whereas the CM-Pf is part of an indirect, internal loop of the basal ganglia circuitry, according to the investigators.

The current study was also by Dr. Marie-Laure Welter and was sponsored by the French National Institute for Health and Medical Research, the University of Pierre and Marie Curie in Paris, and the Public Assistance Hospital of Paris.

CHICAGO – Preliminary data from two trials suggest that deep brain stimulation may be superior to the best medical therapy in Parkinson's disease, and that stimulating specific targets may lead to different cognitive and mood outcomes.

Complete data on 230 of 255 patients with idiopathic Parkinson's disease showed that motor functioning at 6 months, based on blinded ratings, improved 35.6% over baseline with deep brain stimulation (DBS), but only 4.5% with the best medical therapy (BMT), Frances M. Weaver, Ph.D., co-principal investigator, reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Time without troublesome dyskinesia increased by 5.1 hours with DBS, compared with no change with BMT.

The 111 DBS patients experienced significant improvement in all aspects of the Parkinson's Disease Questionnaire-39, except for social support, compared with the 119 BMT patients who had little change.

However, these gains must be weighed against the greater risk of serious adverse events following DBS, Dr. Weaver reported on behalf of the Veterans Affairs/National Institute of Neurological Disorders and Stroke (VA/NINDS-01) Study Group.

At least one serious adverse event was experienced by 40% of DBS patients, compared with only 11% of BMT patients.

The Deep Brain Stimulation vs. Best Medical Therapy trial included patients aged 22 years or older (mean age 63 years) with Hoehn and Yahr stage 2 or greater idiopathic Parkinson's disease responsive to L-dopa, but with persistent motor complications. BMT patients received optimized medical therapy, and DBS patients were further randomized to bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus interna (GPi).

The BMT arm was discontinued early as there was sufficient power to compare the primary outcome with the first 255 patients. Most BMT patients proceeded to surgical treatment, Dr. Weaver, of Hines (Ill.) Veterans Affairs Hospital, said in an interview. Results of the DBS target (STN vs. GPi) portion of the trial are expected in 2009.

Results from the prospective, randomized COMPARE (Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease) trial will not end the controversy over which surgical target is best, but will provide the first level 1 evidence that may allow physicians to tailor DBS to the patient's symptoms, said Dr. Michael S. Okun, co-principal investigator.

“We should stop thinking of these comparisons as yes-or-no phenomena, but start to think of where one target might be better than another and match our patients up so they can achieve optimal benefit,” he said.

Six-month data on 45 of 52 patients (mean age 61 years) showed no significant difference between 22 STN and 23 GPi patients in seven of the eight subscales of the visual analog mood scale (VAMS), the primary outcome of the study. There was a significant difference between groups on the VAMS anger subscale; the mean change in anger scores was significantly larger with STN than with GPi (5.4 vs. −0.2).

Both groups reported significant improvements in VAMS scores on the tension and tiredness subscales, but the difference between groups was not significant.

Significant worsening of verbal fluency was seen in the STN group but not with GPi (−5.6 vs. 0.4). This was true whether the stimulator was on or off. The pattern of deterioration in the STN group preliminarily suggested a surgical or lesional effect rather than a stimulation-induced effect, said Dr. Okun, codirector of the movement disorders center at the University of Florida, Gainesville, and national medical director for the National Parkinson's Foundation.

Both groups reported being significantly less happy, less energetic, and more confused when stimulation was delivered ventrally or one contact below the optimal stimulation site.

No significant difference was found in motor improvement between the STN and GPi groups (mean 29.9% vs. 26.6%), while medication reduction trended in favor of STN; however, the study was not powered for these outcomes.

There were 95 surgical adverse events with STN vs. 67 with GPi. There was one death because of pneumonia in the STN group, said Dr. Okun, who has received speaking and consulting fees from the National Parkinson's Foundation and Medtronic Inc.

Full results of the COMPARE trial, which was funded by the National Institute of Neurological Disorders and Stroke and the University of Florida, are expected in the fall of 2008.

Additional level 1 evidence on DBS is expected later this year from the double-blind, prospective Deep Brain Stimulation for Parkinson's Disease trial comparing unilateral STN with GPi in 121 patients. Preliminary analysis of motor scores data at 6 months revealed no significant difference between the two target sites (STN and GPi), the trial's principal investigator, Dr. Jerrold Vitek of the Cleveland Clinic Foundation, said in an interview. Data verification is ongoing, and formal analyses will address a number of issues including neuropsychological and psychiatric functioning, quality-of-life parameters, and other secondary variables.

Patients were randomized based on motor symptom symmetry to determine if this factor can be used to decide whether patients require bilateral surgery or whether some may do well with just unilateral stimulation, thereby decreasing the risk and cost of treatment, he said.

CHICAGO – Preliminary data from two trials suggest that deep brain stimulation may be superior to the best medical therapy in Parkinson's disease, and that stimulating specific targets may lead to different cognitive and mood outcomes.

Complete data on 230 of 255 patients with idiopathic Parkinson's disease showed that motor functioning at 6 months, based on blinded ratings, improved 35.6% over baseline with deep brain stimulation (DBS), but only 4.5% with the best medical therapy (BMT), Frances M. Weaver, Ph.D., co-principal investigator, reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Time without troublesome dyskinesia increased by 5.1 hours with DBS, compared with no change with BMT.

The 111 DBS patients experienced significant improvement in all aspects of the Parkinson's Disease Questionnaire-39, except for social support, compared with the 119 BMT patients who had little change.

However, these gains must be weighed against the greater risk of serious adverse events following DBS, Dr. Weaver reported on behalf of the Veterans Affairs/National Institute of Neurological Disorders and Stroke (VA/NINDS-01) Study Group.

At least one serious adverse event was experienced by 40% of DBS patients, compared with only 11% of BMT patients.

The Deep Brain Stimulation vs. Best Medical Therapy trial included patients aged 22 years or older (mean age 63 years) with Hoehn and Yahr stage 2 or greater idiopathic Parkinson's disease responsive to L-dopa, but with persistent motor complications. BMT patients received optimized medical therapy, and DBS patients were further randomized to bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus interna (GPi).

The BMT arm was discontinued early as there was sufficient power to compare the primary outcome with the first 255 patients. Most BMT patients proceeded to surgical treatment, Dr. Weaver, of Hines (Ill.) Veterans Affairs Hospital, said in an interview. Results of the DBS target (STN vs. GPi) portion of the trial are expected in 2009.

Results from the prospective, randomized COMPARE (Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease) trial will not end the controversy over which surgical target is best, but will provide the first level 1 evidence that may allow physicians to tailor DBS to the patient's symptoms, said Dr. Michael S. Okun, co-principal investigator.

“We should stop thinking of these comparisons as yes-or-no phenomena, but start to think of where one target might be better than another and match our patients up so they can achieve optimal benefit,” he said.

Six-month data on 45 of 52 patients (mean age 61 years) showed no significant difference between 22 STN and 23 GPi patients in seven of the eight subscales of the visual analog mood scale (VAMS), the primary outcome of the study. There was a significant difference between groups on the VAMS anger subscale; the mean change in anger scores was significantly larger with STN than with GPi (5.4 vs. −0.2).

Both groups reported significant improvements in VAMS scores on the tension and tiredness subscales, but the difference between groups was not significant.

Significant worsening of verbal fluency was seen in the STN group but not with GPi (−5.6 vs. 0.4). This was true whether the stimulator was on or off. The pattern of deterioration in the STN group preliminarily suggested a surgical or lesional effect rather than a stimulation-induced effect, said Dr. Okun, codirector of the movement disorders center at the University of Florida, Gainesville, and national medical director for the National Parkinson's Foundation.

Both groups reported being significantly less happy, less energetic, and more confused when stimulation was delivered ventrally or one contact below the optimal stimulation site.

No significant difference was found in motor improvement between the STN and GPi groups (mean 29.9% vs. 26.6%), while medication reduction trended in favor of STN; however, the study was not powered for these outcomes.

There were 95 surgical adverse events with STN vs. 67 with GPi. There was one death because of pneumonia in the STN group, said Dr. Okun, who has received speaking and consulting fees from the National Parkinson's Foundation and Medtronic Inc.

Full results of the COMPARE trial, which was funded by the National Institute of Neurological Disorders and Stroke and the University of Florida, are expected in the fall of 2008.

Additional level 1 evidence on DBS is expected later this year from the double-blind, prospective Deep Brain Stimulation for Parkinson's Disease trial comparing unilateral STN with GPi in 121 patients. Preliminary analysis of motor scores data at 6 months revealed no significant difference between the two target sites (STN and GPi), the trial's principal investigator, Dr. Jerrold Vitek of the Cleveland Clinic Foundation, said in an interview. Data verification is ongoing, and formal analyses will address a number of issues including neuropsychological and psychiatric functioning, quality-of-life parameters, and other secondary variables.

Patients were randomized based on motor symptom symmetry to determine if this factor can be used to decide whether patients require bilateral surgery or whether some may do well with just unilateral stimulation, thereby decreasing the risk and cost of treatment, he said.

CHICAGO – Preliminary data from two trials suggest that deep brain stimulation may be superior to the best medical therapy in Parkinson's disease, and that stimulating specific targets may lead to different cognitive and mood outcomes.

Complete data on 230 of 255 patients with idiopathic Parkinson's disease showed that motor functioning at 6 months, based on blinded ratings, improved 35.6% over baseline with deep brain stimulation (DBS), but only 4.5% with the best medical therapy (BMT), Frances M. Weaver, Ph.D., co-principal investigator, reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Time without troublesome dyskinesia increased by 5.1 hours with DBS, compared with no change with BMT.

The 111 DBS patients experienced significant improvement in all aspects of the Parkinson's Disease Questionnaire-39, except for social support, compared with the 119 BMT patients who had little change.

However, these gains must be weighed against the greater risk of serious adverse events following DBS, Dr. Weaver reported on behalf of the Veterans Affairs/National Institute of Neurological Disorders and Stroke (VA/NINDS-01) Study Group.

At least one serious adverse event was experienced by 40% of DBS patients, compared with only 11% of BMT patients.

The Deep Brain Stimulation vs. Best Medical Therapy trial included patients aged 22 years or older (mean age 63 years) with Hoehn and Yahr stage 2 or greater idiopathic Parkinson's disease responsive to L-dopa, but with persistent motor complications. BMT patients received optimized medical therapy, and DBS patients were further randomized to bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus interna (GPi).

The BMT arm was discontinued early as there was sufficient power to compare the primary outcome with the first 255 patients. Most BMT patients proceeded to surgical treatment, Dr. Weaver, of Hines (Ill.) Veterans Affairs Hospital, said in an interview. Results of the DBS target (STN vs. GPi) portion of the trial are expected in 2009.

Results from the prospective, randomized COMPARE (Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease) trial will not end the controversy over which surgical target is best, but will provide the first level 1 evidence that may allow physicians to tailor DBS to the patient's symptoms, said Dr. Michael S. Okun, co-principal investigator.

“We should stop thinking of these comparisons as yes-or-no phenomena, but start to think of where one target might be better than another and match our patients up so they can achieve optimal benefit,” he said.

Six-month data on 45 of 52 patients (mean age 61 years) showed no significant difference between 22 STN and 23 GPi patients in seven of the eight subscales of the visual analog mood scale (VAMS), the primary outcome of the study. There was a significant difference between groups on the VAMS anger subscale; the mean change in anger scores was significantly larger with STN than with GPi (5.4 vs. −0.2).

Both groups reported significant improvements in VAMS scores on the tension and tiredness subscales, but the difference between groups was not significant.

Significant worsening of verbal fluency was seen in the STN group but not with GPi (−5.6 vs. 0.4). This was true whether the stimulator was on or off. The pattern of deterioration in the STN group preliminarily suggested a surgical or lesional effect rather than a stimulation-induced effect, said Dr. Okun, codirector of the movement disorders center at the University of Florida, Gainesville, and national medical director for the National Parkinson's Foundation.

Both groups reported being significantly less happy, less energetic, and more confused when stimulation was delivered ventrally or one contact below the optimal stimulation site.

No significant difference was found in motor improvement between the STN and GPi groups (mean 29.9% vs. 26.6%), while medication reduction trended in favor of STN; however, the study was not powered for these outcomes.

There were 95 surgical adverse events with STN vs. 67 with GPi. There was one death because of pneumonia in the STN group, said Dr. Okun, who has received speaking and consulting fees from the National Parkinson's Foundation and Medtronic Inc.

Full results of the COMPARE trial, which was funded by the National Institute of Neurological Disorders and Stroke and the University of Florida, are expected in the fall of 2008.

Additional level 1 evidence on DBS is expected later this year from the double-blind, prospective Deep Brain Stimulation for Parkinson's Disease trial comparing unilateral STN with GPi in 121 patients. Preliminary analysis of motor scores data at 6 months revealed no significant difference between the two target sites (STN and GPi), the trial's principal investigator, Dr. Jerrold Vitek of the Cleveland Clinic Foundation, said in an interview. Data verification is ongoing, and formal analyses will address a number of issues including neuropsychological and psychiatric functioning, quality-of-life parameters, and other secondary variables.

Patients were randomized based on motor symptom symmetry to determine if this factor can be used to decide whether patients require bilateral surgery or whether some may do well with just unilateral stimulation, thereby decreasing the risk and cost of treatment, he said.

CHICAGO — The novel skin substitutes Suprathel and Matriderm resulted in complete healing and excellent functionality in patients with deep burns in two studies.

By using Suprathel, complete epithelialization was achieved in 14–20 days for 38 of 40 patients with deep dermal burns. Regrafting was necessary in only two patients, said Dr. David Lumenta, who presented the results on behalf of Dr. Lars-Peter Kamolz at the annual meeting of the American Burn Association. Both are with the division of plastic and reconstructive surgery at the Medical University of Vienna.

Average total body surface area burned (TBSA) was 35%, although the team has used Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany) in patients with burns up to 90% TBSA.

Suprathel is a resorbable skin substitute produced from a fully synthetic copolymer with a porous membrane, based largely (greater than 70%) on poly-DL-lactide. It is available in various pore and surface sizes and is indicated mainly for use on donor sites and partial-thickness burns.

Its main advantages are reduced pain, accelerated epithelialization, and employment in functionally stressed regions and joints. It is more easily handled than other biologic dressings, and there is no biological risk, Dr. Lumenta said. No signs of local or systemic allergic reaction were observed in the 40 patients.

In a poster at the same meeting, Dr. Kamolz reported their experience with Matriderm in 10 patients with severe hand burns.

Matriderm (Dr. Suwelack Skin & Health Care AG, Billerbeck, Germany) is a thin, porous membrane consisting of a native bovine type I, II, and V collagen-fiber template coated with elastin hydrolysate, which is converted into native host collagen within weeks of application, Dr. Kamolz said in an interview.

The matrix serves as a support structure for new cell growth while the collagen improves the stability and elasticity of the regenerating tissue. As healing progresses, fibroblasts produce their own extracellular matrix and Matriderm is resorbed. The main indications for this matrix are full-thickness burns in functionally and aesthetically important regions, he said.

A two-step repair is recommended for Matriderm sheets 2 mm or greater in thickness, with a 7-day interval between matrix application and transplantation of split-thickness skin grafts to allow for vascularization of the matrix. A single operation is feasible in the acute phase after burn trauma using a 1-mm-thick sheet.

The take-rate using Matriderm does not differ significantly, compared with traditional split-thickness skin grafts, and the quality of the resulting scar has been superior, Dr. Kamolz said.

The take-rate was 97% at 3 months' follow-up among 10 patients, mean age 45 years, with severe, full-thickness hand burns (TBSA 23%) who underwent early debridement and immediate grafting with Matriderm and an unmeshed skin graft in a single operation.

The pliability of the grafted area was excellent, with a mean Vancouver Scar Scale score of 3.2. Full range of motion was achieved in all hands, he said.

No blisters and no unstable or hypertrophic scars were observed. In comparison with conventional skin grafts, the color of the skin grafts over the matrix appeared pale during the first few days, but no difference was observed after 2 weeks.

"These good functional and aesthetic results remain stable, even 12 months postoperatively," he reported.

The study was supported by the Medical University of Vienna. The investigators disclosed no relevant conflicts of interest. Neither product has been approved for use in the United States.

A patient whose severe hand burns (left) were treated with Matriderm grafting showed free range of motion and good function at 1 year. Photos courtesy Dr. Lars-Peter Kamolz

CHICAGO — The novel skin substitutes Suprathel and Matriderm resulted in complete healing and excellent functionality in patients with deep burns in two studies.

By using Suprathel, complete epithelialization was achieved in 14–20 days for 38 of 40 patients with deep dermal burns. Regrafting was necessary in only two patients, said Dr. David Lumenta, who presented the results on behalf of Dr. Lars-Peter Kamolz at the annual meeting of the American Burn Association. Both are with the division of plastic and reconstructive surgery at the Medical University of Vienna.

Average total body surface area burned (TBSA) was 35%, although the team has used Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany) in patients with burns up to 90% TBSA.

Suprathel is a resorbable skin substitute produced from a fully synthetic copolymer with a porous membrane, based largely (greater than 70%) on poly-DL-lactide. It is available in various pore and surface sizes and is indicated mainly for use on donor sites and partial-thickness burns.

Its main advantages are reduced pain, accelerated epithelialization, and employment in functionally stressed regions and joints. It is more easily handled than other biologic dressings, and there is no biological risk, Dr. Lumenta said. No signs of local or systemic allergic reaction were observed in the 40 patients.

In a poster at the same meeting, Dr. Kamolz reported their experience with Matriderm in 10 patients with severe hand burns.

Matriderm (Dr. Suwelack Skin & Health Care AG, Billerbeck, Germany) is a thin, porous membrane consisting of a native bovine type I, II, and V collagen-fiber template coated with elastin hydrolysate, which is converted into native host collagen within weeks of application, Dr. Kamolz said in an interview.

The matrix serves as a support structure for new cell growth while the collagen improves the stability and elasticity of the regenerating tissue. As healing progresses, fibroblasts produce their own extracellular matrix and Matriderm is resorbed. The main indications for this matrix are full-thickness burns in functionally and aesthetically important regions, he said.

A two-step repair is recommended for Matriderm sheets 2 mm or greater in thickness, with a 7-day interval between matrix application and transplantation of split-thickness skin grafts to allow for vascularization of the matrix. A single operation is feasible in the acute phase after burn trauma using a 1-mm-thick sheet.

The take-rate using Matriderm does not differ significantly, compared with traditional split-thickness skin grafts, and the quality of the resulting scar has been superior, Dr. Kamolz said.

The take-rate was 97% at 3 months' follow-up among 10 patients, mean age 45 years, with severe, full-thickness hand burns (TBSA 23%) who underwent early debridement and immediate grafting with Matriderm and an unmeshed skin graft in a single operation.

The pliability of the grafted area was excellent, with a mean Vancouver Scar Scale score of 3.2. Full range of motion was achieved in all hands, he said.

No blisters and no unstable or hypertrophic scars were observed. In comparison with conventional skin grafts, the color of the skin grafts over the matrix appeared pale during the first few days, but no difference was observed after 2 weeks.

"These good functional and aesthetic results remain stable, even 12 months postoperatively," he reported.

The study was supported by the Medical University of Vienna. The investigators disclosed no relevant conflicts of interest. Neither product has been approved for use in the United States.

A patient whose severe hand burns (left) were treated with Matriderm grafting showed free range of motion and good function at 1 year. Photos courtesy Dr. Lars-Peter Kamolz

CHICAGO — The novel skin substitutes Suprathel and Matriderm resulted in complete healing and excellent functionality in patients with deep burns in two studies.

By using Suprathel, complete epithelialization was achieved in 14–20 days for 38 of 40 patients with deep dermal burns. Regrafting was necessary in only two patients, said Dr. David Lumenta, who presented the results on behalf of Dr. Lars-Peter Kamolz at the annual meeting of the American Burn Association. Both are with the division of plastic and reconstructive surgery at the Medical University of Vienna.

Average total body surface area burned (TBSA) was 35%, although the team has used Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany) in patients with burns up to 90% TBSA.

Suprathel is a resorbable skin substitute produced from a fully synthetic copolymer with a porous membrane, based largely (greater than 70%) on poly-DL-lactide. It is available in various pore and surface sizes and is indicated mainly for use on donor sites and partial-thickness burns.

Its main advantages are reduced pain, accelerated epithelialization, and employment in functionally stressed regions and joints. It is more easily handled than other biologic dressings, and there is no biological risk, Dr. Lumenta said. No signs of local or systemic allergic reaction were observed in the 40 patients.

In a poster at the same meeting, Dr. Kamolz reported their experience with Matriderm in 10 patients with severe hand burns.

Matriderm (Dr. Suwelack Skin & Health Care AG, Billerbeck, Germany) is a thin, porous membrane consisting of a native bovine type I, II, and V collagen-fiber template coated with elastin hydrolysate, which is converted into native host collagen within weeks of application, Dr. Kamolz said in an interview.

The matrix serves as a support structure for new cell growth while the collagen improves the stability and elasticity of the regenerating tissue. As healing progresses, fibroblasts produce their own extracellular matrix and Matriderm is resorbed. The main indications for this matrix are full-thickness burns in functionally and aesthetically important regions, he said.

A two-step repair is recommended for Matriderm sheets 2 mm or greater in thickness, with a 7-day interval between matrix application and transplantation of split-thickness skin grafts to allow for vascularization of the matrix. A single operation is feasible in the acute phase after burn trauma using a 1-mm-thick sheet.

The take-rate using Matriderm does not differ significantly, compared with traditional split-thickness skin grafts, and the quality of the resulting scar has been superior, Dr. Kamolz said.

The take-rate was 97% at 3 months' follow-up among 10 patients, mean age 45 years, with severe, full-thickness hand burns (TBSA 23%) who underwent early debridement and immediate grafting with Matriderm and an unmeshed skin graft in a single operation.

The pliability of the grafted area was excellent, with a mean Vancouver Scar Scale score of 3.2. Full range of motion was achieved in all hands, he said.

No blisters and no unstable or hypertrophic scars were observed. In comparison with conventional skin grafts, the color of the skin grafts over the matrix appeared pale during the first few days, but no difference was observed after 2 weeks.

"These good functional and aesthetic results remain stable, even 12 months postoperatively," he reported.

The study was supported by the Medical University of Vienna. The investigators disclosed no relevant conflicts of interest. Neither product has been approved for use in the United States.

A patient whose severe hand burns (left) were treated with Matriderm grafting showed free range of motion and good function at 1 year. Photos courtesy Dr. Lars-Peter Kamolz

CHICAGO — The investigational agent pimavanserin appears to lessen psychosis in patients with Parkinson's disease without worsening motor function, according to a multicenter randomized phase II trial.

Pimavanserin is a potent, active 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor antagonist, said Dr. Stephen Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D2) and histamine receptor (H1) binding linked to the adverse effects of other antipsychotics.

Patients in the study had PD and psychosis and were given either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Pimavanserin patients demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, compared with an 11% improvement for placebo patients (P = .05), Dr. Revell reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were seen for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS) (P = .05).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in the absolute mean change from baseline to day 28 in UPDRS motor scores (-3.05 vs. −1.24, P = .303) or activities of daily living scores (-2.51 vs. −0.70, P = .112).

No differences in the groups were seen on the Schwab and England Activities of Daily Living Scale part of the UPDRS, the Clinical Global Impression Scale severity of illness subscale, or the Epworth Sleepiness Scale daytime sleepiness subscale. The most common adverse events were somnolence, edema, and increased blood urea.

In a second poster, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72) with PD and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Somnolence, fatigue, or dizziness were uncommon, said Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

A case of rhabdomyolysis was the only serious adverse event.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The investigational agent pimavanserin appears to lessen psychosis in patients with Parkinson's disease without worsening motor function, according to a multicenter randomized phase II trial.

Pimavanserin is a potent, active 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor antagonist, said Dr. Stephen Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D2) and histamine receptor (H1) binding linked to the adverse effects of other antipsychotics.

Patients in the study had PD and psychosis and were given either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Pimavanserin patients demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, compared with an 11% improvement for placebo patients (P = .05), Dr. Revell reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were seen for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS) (P = .05).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in the absolute mean change from baseline to day 28 in UPDRS motor scores (-3.05 vs. −1.24, P = .303) or activities of daily living scores (-2.51 vs. −0.70, P = .112).

No differences in the groups were seen on the Schwab and England Activities of Daily Living Scale part of the UPDRS, the Clinical Global Impression Scale severity of illness subscale, or the Epworth Sleepiness Scale daytime sleepiness subscale. The most common adverse events were somnolence, edema, and increased blood urea.

In a second poster, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72) with PD and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Somnolence, fatigue, or dizziness were uncommon, said Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

A case of rhabdomyolysis was the only serious adverse event.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The investigational agent pimavanserin appears to lessen psychosis in patients with Parkinson's disease without worsening motor function, according to a multicenter randomized phase II trial.

Pimavanserin is a potent, active 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor antagonist, said Dr. Stephen Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D2) and histamine receptor (H1) binding linked to the adverse effects of other antipsychotics.

Patients in the study had PD and psychosis and were given either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.

Pimavanserin patients demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, compared with an 11% improvement for placebo patients (P = .05), Dr. Revell reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Statistically significant improvements also were seen for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS) (P = .05).

There was no clinically significant difference between patients treated with placebo vs. pimavanserin in the absolute mean change from baseline to day 28 in UPDRS motor scores (-3.05 vs. −1.24, P = .303) or activities of daily living scores (-2.51 vs. −0.70, P = .112).

No differences in the groups were seen on the Schwab and England Activities of Daily Living Scale part of the UPDRS, the Clinical Global Impression Scale severity of illness subscale, or the Epworth Sleepiness Scale daytime sleepiness subscale. The most common adverse events were somnolence, edema, and increased blood urea.

In a second poster, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72) with PD and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Somnolence, fatigue, or dizziness were uncommon, said Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.

A case of rhabdomyolysis was the only serious adverse event.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – Evidence continues to mount that dopaminergic therapy increases the odds of impulse control disorders in patients who have Parkinson's disease.

Dopamine agonist (DA)-treated patients had two- to threefold elevated odds of having a current impulse control disorder (ICD), compared with non-DA-treated patients (17% vs. 7%) in an international, cross-sectional study of 3,090 patients with idiopathic Parkinson's disease.

This pattern was observed across all four impulse control disorders assessed: pathological gambling (3.5% vs. 1.6%), compulsive sexual behavior (4.4% vs. 1.7%), compulsive buying (7.2% vs. 2.9%), and binge-eating disorder (5.6% vs. 1.7%), Dr. Daniel Weintraub and associates reported in a late-breaking poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Previous case reports and cross-sectional studies have suggested an association between DA treatment and ICDs in Parkinson's disease. However, those previous reports have typically assessed convenience samples of patients, have had relatively small sample sizes, and have not concurrently assessed for all commonly reported ICDs in Parkinson's, according to Dr. Weintraub, who is a psychiatrist affiliated with the University of Pennsylvania, Philadelphia.

Patients in the current study were prospectively recruited from 46 movement disorder centers in the United States and Canada, and assessed using a modified Massachusetts Gambling Screen, a modified Minnesota Impulsive Disorders Interview for compulsive sexual behavior and buying, and DSM-IV Text-Revised proposed research criteria for binge eating.

Their mean age was 64 years. Four hundred and twenty patients (14%) had at least one current ICD, and 36% of patients with an ICD had more than one.

According to Dr. Weintraub, ICD frequencies were similar in patients who were treated with pramipexole, ropinerole, and pergolide, suggesting that DA treatment as a class might be a risk factor for ICD development in Parkinson's disease, the authors concluded.

An ICD was present in 18% of the patients taking both a DA and levodopa, 14% of the patients taking a DA without levodopa, and 7% of the patients taking levodopa without a DA.

Based on the overall findings, Dr. Weintraub said that physicians should notify patients in advance that ICDs are a potential adverse event associated with dopamine-agonist and levodopa treatment, and should conduct routine questioning in the context of clinical care.

“That may help identify patients very early in the process, so adjustments to treatment can be made,” he said in an interview. “Once someone has a full-blown disorder, different treatment strategies at this point include decreasing the dosage of the presumed offending agent, switching to a different class of medication, or coming off that medication completely,” he said. “If patients are appropriate for deep brain stimulation, that often enables them to take a lower dose of the medication.”

Dr. Weintraub acknowledged that ICDs have been reported as a complication of deep brain stimulation, but said most patients with an ICD prior to surgery do better after surgery, probably because of decreased medication.

In a logistic regression analysis, independent risk factors for ICD development included: age of 65 years or younger, DA treatment, and higher DA dosage (greater than 150 mg), levodopa treatment, and higher levodopa dosage (greater than 450 mg), not being married, and self-reported family history of gambling problems.

The study was funded by Boehringer Ingelheim.

Dr. Weintraub has received consulting fees, honoraria, or grant support from Boehringer Ingelheim, BrainCells, EMD Serono, Novartis, Ovation, and Wyeth.

CHICAGO – Evidence continues to mount that dopaminergic therapy increases the odds of impulse control disorders in patients who have Parkinson's disease.

Dopamine agonist (DA)-treated patients had two- to threefold elevated odds of having a current impulse control disorder (ICD), compared with non-DA-treated patients (17% vs. 7%) in an international, cross-sectional study of 3,090 patients with idiopathic Parkinson's disease.

This pattern was observed across all four impulse control disorders assessed: pathological gambling (3.5% vs. 1.6%), compulsive sexual behavior (4.4% vs. 1.7%), compulsive buying (7.2% vs. 2.9%), and binge-eating disorder (5.6% vs. 1.7%), Dr. Daniel Weintraub and associates reported in a late-breaking poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Previous case reports and cross-sectional studies have suggested an association between DA treatment and ICDs in Parkinson's disease. However, those previous reports have typically assessed convenience samples of patients, have had relatively small sample sizes, and have not concurrently assessed for all commonly reported ICDs in Parkinson's, according to Dr. Weintraub, who is a psychiatrist affiliated with the University of Pennsylvania, Philadelphia.

Patients in the current study were prospectively recruited from 46 movement disorder centers in the United States and Canada, and assessed using a modified Massachusetts Gambling Screen, a modified Minnesota Impulsive Disorders Interview for compulsive sexual behavior and buying, and DSM-IV Text-Revised proposed research criteria for binge eating.

Their mean age was 64 years. Four hundred and twenty patients (14%) had at least one current ICD, and 36% of patients with an ICD had more than one.

According to Dr. Weintraub, ICD frequencies were similar in patients who were treated with pramipexole, ropinerole, and pergolide, suggesting that DA treatment as a class might be a risk factor for ICD development in Parkinson's disease, the authors concluded.

An ICD was present in 18% of the patients taking both a DA and levodopa, 14% of the patients taking a DA without levodopa, and 7% of the patients taking levodopa without a DA.

Based on the overall findings, Dr. Weintraub said that physicians should notify patients in advance that ICDs are a potential adverse event associated with dopamine-agonist and levodopa treatment, and should conduct routine questioning in the context of clinical care.

“That may help identify patients very early in the process, so adjustments to treatment can be made,” he said in an interview. “Once someone has a full-blown disorder, different treatment strategies at this point include decreasing the dosage of the presumed offending agent, switching to a different class of medication, or coming off that medication completely,” he said. “If patients are appropriate for deep brain stimulation, that often enables them to take a lower dose of the medication.”

Dr. Weintraub acknowledged that ICDs have been reported as a complication of deep brain stimulation, but said most patients with an ICD prior to surgery do better after surgery, probably because of decreased medication.

In a logistic regression analysis, independent risk factors for ICD development included: age of 65 years or younger, DA treatment, and higher DA dosage (greater than 150 mg), levodopa treatment, and higher levodopa dosage (greater than 450 mg), not being married, and self-reported family history of gambling problems.

The study was funded by Boehringer Ingelheim.

Dr. Weintraub has received consulting fees, honoraria, or grant support from Boehringer Ingelheim, BrainCells, EMD Serono, Novartis, Ovation, and Wyeth.

CHICAGO – Evidence continues to mount that dopaminergic therapy increases the odds of impulse control disorders in patients who have Parkinson's disease.

Dopamine agonist (DA)-treated patients had two- to threefold elevated odds of having a current impulse control disorder (ICD), compared with non-DA-treated patients (17% vs. 7%) in an international, cross-sectional study of 3,090 patients with idiopathic Parkinson's disease.

This pattern was observed across all four impulse control disorders assessed: pathological gambling (3.5% vs. 1.6%), compulsive sexual behavior (4.4% vs. 1.7%), compulsive buying (7.2% vs. 2.9%), and binge-eating disorder (5.6% vs. 1.7%), Dr. Daniel Weintraub and associates reported in a late-breaking poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Previous case reports and cross-sectional studies have suggested an association between DA treatment and ICDs in Parkinson's disease. However, those previous reports have typically assessed convenience samples of patients, have had relatively small sample sizes, and have not concurrently assessed for all commonly reported ICDs in Parkinson's, according to Dr. Weintraub, who is a psychiatrist affiliated with the University of Pennsylvania, Philadelphia.

Patients in the current study were prospectively recruited from 46 movement disorder centers in the United States and Canada, and assessed using a modified Massachusetts Gambling Screen, a modified Minnesota Impulsive Disorders Interview for compulsive sexual behavior and buying, and DSM-IV Text-Revised proposed research criteria for binge eating.

Their mean age was 64 years. Four hundred and twenty patients (14%) had at least one current ICD, and 36% of patients with an ICD had more than one.

According to Dr. Weintraub, ICD frequencies were similar in patients who were treated with pramipexole, ropinerole, and pergolide, suggesting that DA treatment as a class might be a risk factor for ICD development in Parkinson's disease, the authors concluded.

An ICD was present in 18% of the patients taking both a DA and levodopa, 14% of the patients taking a DA without levodopa, and 7% of the patients taking levodopa without a DA.

Based on the overall findings, Dr. Weintraub said that physicians should notify patients in advance that ICDs are a potential adverse event associated with dopamine-agonist and levodopa treatment, and should conduct routine questioning in the context of clinical care.

“That may help identify patients very early in the process, so adjustments to treatment can be made,” he said in an interview. “Once someone has a full-blown disorder, different treatment strategies at this point include decreasing the dosage of the presumed offending agent, switching to a different class of medication, or coming off that medication completely,” he said. “If patients are appropriate for deep brain stimulation, that often enables them to take a lower dose of the medication.”

Dr. Weintraub acknowledged that ICDs have been reported as a complication of deep brain stimulation, but said most patients with an ICD prior to surgery do better after surgery, probably because of decreased medication.

In a logistic regression analysis, independent risk factors for ICD development included: age of 65 years or younger, DA treatment, and higher DA dosage (greater than 150 mg), levodopa treatment, and higher levodopa dosage (greater than 450 mg), not being married, and self-reported family history of gambling problems.

The study was funded by Boehringer Ingelheim.

Dr. Weintraub has received consulting fees, honoraria, or grant support from Boehringer Ingelheim, BrainCells, EMD Serono, Novartis, Ovation, and Wyeth.