Bianca Nogrady

Adalimumab is safe and effective as both a first- and second-line biologic agent in patients with juvenile idiopathic arthritis, according to data presented by Dr. Gerd Horneff.

Dr. Horneff from the Asklepios Klinik, St. Augustin, Germany, and Dr. Heinrike Schmeling from the Alberta Children’s Hospital, Calgary, analyzed data from 329 children aged 4-18 years with juvenile idiopathic arthritis (JIA) in the German Biologics Register, finding that a high proportion of patients showed a significant response to treatment with adalimumab.

"The results of this study indicate that adalimumab is highly effective as a first and also as a second introduced biological agent resulting in substantial improvements in clinical signs and symptoms in children with juvenile idiopathic arthritis," Dr. Schmeling said in an interview prior to the annual European Congress of Rheumatology.

Even patients who were using adalimumab as a second or third biologic gained an additional response to adalimumab on top of their responses to previous biologics. The percentage of patients who met the criteria of 30%/50%/70% improvement at last documentation when adalimumab was the first introduced biologic agent was 65%/61%/46%, compared with 73%/65%/48% when adalimumab was initiated after other biologics, the investigators reported.

Around one-third of patients had rheumatoid factor–negative polyarticular JIA, 22.9% had extended oligoarticular JIA, and 25.2% of patients had a history of uveitis.

The median age of onset of disease was 6.7 years, and median age at treatment initiation was 13.8 years, with median disease duration of 5.1 years. ANA positivity was present in 51% of patients and HLB27 positivity in 19.8%. Most patients had been previously treated with methotrexate (92.4%), approximately one-third had received other disease-modifying antirheumatic drugs (DMARDs), and two-thirds had been treated with biologics, mostly etanercept.

Many were also receiving concomitant treatment with NSAIDs (55.3%), steroids (38%), methotrexate (57.8%), and other DMARDs (13%).

However, Dr. Schmeling emphasized that this study was not an attempt to compare adalimumab to other biologic treatments.

While no malignancies were observed during adalimumab treatment, 96 patients reported 220 adverse events, 14 of which were serious. There were also more autoimmune adverse events among patients treated with adalimumab, but Dr. Schmeling said the numbers were too small to draw any conclusions.

Uveitis developed in 18 children while on treatment, 13 of them had a history of uveitis prior to adalimumab initiation. Treatment was discontinued in 61 patients because of inefficacy (9%), adverse events (5%), remission (3%), patient request (9%), and other unspecified reasons (2%).

Disease register is supported by Abbott, Pfizer (Wyeth Pharma), and Roche, Germany. Dr. Schmeling had no financial disclosures. Dr Horneff declared consultancies, speakers bureau engagement, and research support from Abbott, Pfizer, and Roche.

Adalimumab is safe and effective as both a first- and second-line biologic agent in patients with juvenile idiopathic arthritis, according to data presented by Dr. Gerd Horneff.

Dr. Horneff from the Asklepios Klinik, St. Augustin, Germany, and Dr. Heinrike Schmeling from the Alberta Children’s Hospital, Calgary, analyzed data from 329 children aged 4-18 years with juvenile idiopathic arthritis (JIA) in the German Biologics Register, finding that a high proportion of patients showed a significant response to treatment with adalimumab.

"The results of this study indicate that adalimumab is highly effective as a first and also as a second introduced biological agent resulting in substantial improvements in clinical signs and symptoms in children with juvenile idiopathic arthritis," Dr. Schmeling said in an interview prior to the annual European Congress of Rheumatology.

Even patients who were using adalimumab as a second or third biologic gained an additional response to adalimumab on top of their responses to previous biologics. The percentage of patients who met the criteria of 30%/50%/70% improvement at last documentation when adalimumab was the first introduced biologic agent was 65%/61%/46%, compared with 73%/65%/48% when adalimumab was initiated after other biologics, the investigators reported.

Around one-third of patients had rheumatoid factor–negative polyarticular JIA, 22.9% had extended oligoarticular JIA, and 25.2% of patients had a history of uveitis.

The median age of onset of disease was 6.7 years, and median age at treatment initiation was 13.8 years, with median disease duration of 5.1 years. ANA positivity was present in 51% of patients and HLB27 positivity in 19.8%. Most patients had been previously treated with methotrexate (92.4%), approximately one-third had received other disease-modifying antirheumatic drugs (DMARDs), and two-thirds had been treated with biologics, mostly etanercept.

Many were also receiving concomitant treatment with NSAIDs (55.3%), steroids (38%), methotrexate (57.8%), and other DMARDs (13%).

However, Dr. Schmeling emphasized that this study was not an attempt to compare adalimumab to other biologic treatments.

While no malignancies were observed during adalimumab treatment, 96 patients reported 220 adverse events, 14 of which were serious. There were also more autoimmune adverse events among patients treated with adalimumab, but Dr. Schmeling said the numbers were too small to draw any conclusions.

Uveitis developed in 18 children while on treatment, 13 of them had a history of uveitis prior to adalimumab initiation. Treatment was discontinued in 61 patients because of inefficacy (9%), adverse events (5%), remission (3%), patient request (9%), and other unspecified reasons (2%).

Disease register is supported by Abbott, Pfizer (Wyeth Pharma), and Roche, Germany. Dr. Schmeling had no financial disclosures. Dr Horneff declared consultancies, speakers bureau engagement, and research support from Abbott, Pfizer, and Roche.

Adalimumab is safe and effective as both a first- and second-line biologic agent in patients with juvenile idiopathic arthritis, according to data presented by Dr. Gerd Horneff.

Dr. Horneff from the Asklepios Klinik, St. Augustin, Germany, and Dr. Heinrike Schmeling from the Alberta Children’s Hospital, Calgary, analyzed data from 329 children aged 4-18 years with juvenile idiopathic arthritis (JIA) in the German Biologics Register, finding that a high proportion of patients showed a significant response to treatment with adalimumab.

"The results of this study indicate that adalimumab is highly effective as a first and also as a second introduced biological agent resulting in substantial improvements in clinical signs and symptoms in children with juvenile idiopathic arthritis," Dr. Schmeling said in an interview prior to the annual European Congress of Rheumatology.

Even patients who were using adalimumab as a second or third biologic gained an additional response to adalimumab on top of their responses to previous biologics. The percentage of patients who met the criteria of 30%/50%/70% improvement at last documentation when adalimumab was the first introduced biologic agent was 65%/61%/46%, compared with 73%/65%/48% when adalimumab was initiated after other biologics, the investigators reported.

Around one-third of patients had rheumatoid factor–negative polyarticular JIA, 22.9% had extended oligoarticular JIA, and 25.2% of patients had a history of uveitis.

The median age of onset of disease was 6.7 years, and median age at treatment initiation was 13.8 years, with median disease duration of 5.1 years. ANA positivity was present in 51% of patients and HLB27 positivity in 19.8%. Most patients had been previously treated with methotrexate (92.4%), approximately one-third had received other disease-modifying antirheumatic drugs (DMARDs), and two-thirds had been treated with biologics, mostly etanercept.

Many were also receiving concomitant treatment with NSAIDs (55.3%), steroids (38%), methotrexate (57.8%), and other DMARDs (13%).

However, Dr. Schmeling emphasized that this study was not an attempt to compare adalimumab to other biologic treatments.

While no malignancies were observed during adalimumab treatment, 96 patients reported 220 adverse events, 14 of which were serious. There were also more autoimmune adverse events among patients treated with adalimumab, but Dr. Schmeling said the numbers were too small to draw any conclusions.

Uveitis developed in 18 children while on treatment, 13 of them had a history of uveitis prior to adalimumab initiation. Treatment was discontinued in 61 patients because of inefficacy (9%), adverse events (5%), remission (3%), patient request (9%), and other unspecified reasons (2%).

Disease register is supported by Abbott, Pfizer (Wyeth Pharma), and Roche, Germany. Dr. Schmeling had no financial disclosures. Dr Horneff declared consultancies, speakers bureau engagement, and research support from Abbott, Pfizer, and Roche.

Biologics and improved strategies for their use have significantly reduced the relatively high rate of sick leave among patients with rheumatoid arthritis, but more efficient, multiprofessional intervention strategies are still needed to reduce its incidence, Mathilda Bjork, Ph.D., reported at the annual European Congress of Rheumatism.

Dr. Bjork, of Jonkoping University, Sweden, conducted a subanalysis of the Swedish Early Rheumatoid Arthritis cohort study (Swedish acronym – TIRA). The study included patients with early rheumatoid arthritis, and was designed to calculate direct and indirect costs of the disease over a 3-year period. There have been two TIRA cohorts – one in 1996-1998 and one in 2005-2008. All had early disease; they were a mean of 62 years at baseline.

At all follow-up visits, the patients met with a multidisciplinary team including a physician, an occupational therapist and a physiotherapist, and were given individual treatment based on their needs.

Those in the more recent cohort were treated more aggressively with disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate, starting at their first visit. They also received biologics when required.

Dr. Bjork’s study examined sick leave rates between the two TIRA cohorts: 1996-1998 and 2005-2008. The comparison found that sick leave rates in the newer cohort declined about 50% compared to those in the older cohort.

In the early cohort, sick leave rates were stable over the 3-year study period. At baseline, 60% of the patients were taking sick leave due to their RA; that number was unchanged at 3 years.

In the newer cohort, the baseline sick leave rate was similar, with 55% taking leave due to their disease. But at the 3-year follow-up, only 30% were on sick leave.

"I think it’s good news," Dr. Bjork said in an interview. Since both groups were making use of the multidisciplinary team treatment, DMARD treatment appeared to be the main driver behind the difference. "They are being used more frequently and in higher doses, and it’s working."

Dr. Bjork said the study came about not only because RA is associated with such high indirect costs for sick leave, but also because of the direct treatment costs of new medications such as biological agents.

"The rationale behind the study was to explore whether more effective disease control reduces sick leave in a postbiologic cohort compared to a prebiologic cohort, with the potential for compensating some of the increased treatment cost."

The researchers suggested that changes in political policies and the sickness insurance system may also have had some impact on the differences in sick leave between the two cohorts.

Despite the significant reductions in sick leave, she suggested that more could be done to address the persistently high rate of sick leave among individuals with RA.

"The impact of rheumatoid arthritis on an individual’s ability to work is a complex interaction of biological, psychological, social, and occupational factors," she said. "The interventions need to have a wider perspective than the rheumatoid arthritis per se and [should be] done in a close interaction between the patient, clinicians, employers, and policy makers early in the disease process."

Dr. Bjork had no conflicts of interest relevant to the study.

Biologics and improved strategies for their use have significantly reduced the relatively high rate of sick leave among patients with rheumatoid arthritis, but more efficient, multiprofessional intervention strategies are still needed to reduce its incidence, Mathilda Bjork, Ph.D., reported at the annual European Congress of Rheumatism.

Dr. Bjork, of Jonkoping University, Sweden, conducted a subanalysis of the Swedish Early Rheumatoid Arthritis cohort study (Swedish acronym – TIRA). The study included patients with early rheumatoid arthritis, and was designed to calculate direct and indirect costs of the disease over a 3-year period. There have been two TIRA cohorts – one in 1996-1998 and one in 2005-2008. All had early disease; they were a mean of 62 years at baseline.

At all follow-up visits, the patients met with a multidisciplinary team including a physician, an occupational therapist and a physiotherapist, and were given individual treatment based on their needs.

Those in the more recent cohort were treated more aggressively with disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate, starting at their first visit. They also received biologics when required.

Dr. Bjork’s study examined sick leave rates between the two TIRA cohorts: 1996-1998 and 2005-2008. The comparison found that sick leave rates in the newer cohort declined about 50% compared to those in the older cohort.

In the early cohort, sick leave rates were stable over the 3-year study period. At baseline, 60% of the patients were taking sick leave due to their RA; that number was unchanged at 3 years.

In the newer cohort, the baseline sick leave rate was similar, with 55% taking leave due to their disease. But at the 3-year follow-up, only 30% were on sick leave.

"I think it’s good news," Dr. Bjork said in an interview. Since both groups were making use of the multidisciplinary team treatment, DMARD treatment appeared to be the main driver behind the difference. "They are being used more frequently and in higher doses, and it’s working."

Dr. Bjork said the study came about not only because RA is associated with such high indirect costs for sick leave, but also because of the direct treatment costs of new medications such as biological agents.

"The rationale behind the study was to explore whether more effective disease control reduces sick leave in a postbiologic cohort compared to a prebiologic cohort, with the potential for compensating some of the increased treatment cost."

The researchers suggested that changes in political policies and the sickness insurance system may also have had some impact on the differences in sick leave between the two cohorts.

Despite the significant reductions in sick leave, she suggested that more could be done to address the persistently high rate of sick leave among individuals with RA.

"The impact of rheumatoid arthritis on an individual’s ability to work is a complex interaction of biological, psychological, social, and occupational factors," she said. "The interventions need to have a wider perspective than the rheumatoid arthritis per se and [should be] done in a close interaction between the patient, clinicians, employers, and policy makers early in the disease process."

Dr. Bjork had no conflicts of interest relevant to the study.

Biologics and improved strategies for their use have significantly reduced the relatively high rate of sick leave among patients with rheumatoid arthritis, but more efficient, multiprofessional intervention strategies are still needed to reduce its incidence, Mathilda Bjork, Ph.D., reported at the annual European Congress of Rheumatism.

Dr. Bjork, of Jonkoping University, Sweden, conducted a subanalysis of the Swedish Early Rheumatoid Arthritis cohort study (Swedish acronym – TIRA). The study included patients with early rheumatoid arthritis, and was designed to calculate direct and indirect costs of the disease over a 3-year period. There have been two TIRA cohorts – one in 1996-1998 and one in 2005-2008. All had early disease; they were a mean of 62 years at baseline.

At all follow-up visits, the patients met with a multidisciplinary team including a physician, an occupational therapist and a physiotherapist, and were given individual treatment based on their needs.

Those in the more recent cohort were treated more aggressively with disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate, starting at their first visit. They also received biologics when required.

Dr. Bjork’s study examined sick leave rates between the two TIRA cohorts: 1996-1998 and 2005-2008. The comparison found that sick leave rates in the newer cohort declined about 50% compared to those in the older cohort.

In the early cohort, sick leave rates were stable over the 3-year study period. At baseline, 60% of the patients were taking sick leave due to their RA; that number was unchanged at 3 years.

In the newer cohort, the baseline sick leave rate was similar, with 55% taking leave due to their disease. But at the 3-year follow-up, only 30% were on sick leave.

"I think it’s good news," Dr. Bjork said in an interview. Since both groups were making use of the multidisciplinary team treatment, DMARD treatment appeared to be the main driver behind the difference. "They are being used more frequently and in higher doses, and it’s working."

Dr. Bjork said the study came about not only because RA is associated with such high indirect costs for sick leave, but also because of the direct treatment costs of new medications such as biological agents.

"The rationale behind the study was to explore whether more effective disease control reduces sick leave in a postbiologic cohort compared to a prebiologic cohort, with the potential for compensating some of the increased treatment cost."

The researchers suggested that changes in political policies and the sickness insurance system may also have had some impact on the differences in sick leave between the two cohorts.

Despite the significant reductions in sick leave, she suggested that more could be done to address the persistently high rate of sick leave among individuals with RA.

"The impact of rheumatoid arthritis on an individual’s ability to work is a complex interaction of biological, psychological, social, and occupational factors," she said. "The interventions need to have a wider perspective than the rheumatoid arthritis per se and [should be] done in a close interaction between the patient, clinicians, employers, and policy makers early in the disease process."

Dr. Bjork had no conflicts of interest relevant to the study.

Nonpharmacologic interventions such as psychotherapy, hypnosis, and meditation can offer significant benefits to patients with dermatologic conditions including psoriasis, eczema, and urticaria, according to Dr. Richard G. Fried.

While the use of nonpharmacologic interventions may seem counterintuitive, these therapies have been shown to improve psychosocial function and reduce the negative emotional states that can exacerbate or even elicit skin disease, said Dr. Fried of Yardley (Pa.) Dermatology Associates. Dr. Fried detailed several strategies and options for managing the mental aspect of skin disorders in an article in the June issue of Seminars in Cutaneous Medicine and Surgery.

"Clinical studies have demonstrated that psychological stress disrupts skin barrier function and increases the severity of cutaneous infections, and down-regulates antimicrobial peptide expression, resulting in more severe skin infections in mice," Dr. Fried wrote.

"This self-perpetuating negative interaction between stress and impaired skin function has been well-described and often underlies the so-called ‘vicious cycle’ that exists between skin and negative emotional states," he said.

Dr. Fried proposed three broad categories of ‘psychocutaneous’ patients. First, there are individuals with skin manifestations associated a psychiatric diagnosis such as depression, anxiety, or body dysmorphic disorder.

The second category includes patients with psych-derm conditions such as acne excoriée, neurotic excoriations, dermatitis artefacta, and trichotillomania. The third category covers patients with common skin conditions such as acne, rosacea, psoriasis, eczema, and urticaria that are known to be impacted by emotional factors.

Dr. Fried suggested that even patients dealing with the dermatologic effects of aging may be at risk for negative emotional sequelae and may benefit from nonpharmacologic interventions.

Hypnosis is one intervention that has been shown to benefit some patients. For example, long-lasting effects of hypnosis (particularly in highly hypnotizable patients) may include reduced scratching in eczema, and can aid resolution of acne excoriée.

"Recent studies in patients with alopecia areata (including several with ophiasis distribution) demonstrated that hypnosis promotes excellent regrowth in approximately 50% of treated patients and improvements in depression and anxiety in almost all patients," Dr. Fried reported.

Cognitive-behavioral psychotherapy is one of several common psychotherapy interventions used to treat the psychological aspects of skin disorders. Data from a 6-week study of cognitive-behavioral therapy in psoriasis patients showed improvements in anxiety, depression, and psoriasis-related stress, compared with patients who didn’t receive the therapy. In addition, the psychotherapy intervention group showed three times the clinical improvement, compared those undergoing conventional treatment without therapy.

Group psychotherapy has also been associated with symptom reduction, decreased pruritus, fewer eczema relapses, and decreased steroid use in patients with eczema who used it to supplement to their regular medication.

But nonpharmacologic interventions can also be practiced in a less formal manner by dermatologists themselves, Dr. Fried said.

"The power to heal by words, manner, and touch cannot be overstated. Gentle, compassionate, and optimistic comments and gestures can affect the physiology, emotional well-being, and compliance of our patients," he said.

Dr. Fried said referral to a psychodermatologist or mental health professional with an interest in dermatologic manifestations may help some patients, but sometimes treatment can be as simple as a patient’s regular dermatologist offering reassuring words to, "assuage some of the ‘terror of chronicity and progression’ that haunts our patients," he said.

Dr. Fried stated that he has received compensation for the development of educational papers from Ranbaxy, Bayer, Valeant, and Promius.

sknews@frontlinemedcom.com

Nonpharmacologic interventions such as psychotherapy, hypnosis, and meditation can offer significant benefits to patients with dermatologic conditions including psoriasis, eczema, and urticaria, according to Dr. Richard G. Fried.

While the use of nonpharmacologic interventions may seem counterintuitive, these therapies have been shown to improve psychosocial function and reduce the negative emotional states that can exacerbate or even elicit skin disease, said Dr. Fried of Yardley (Pa.) Dermatology Associates. Dr. Fried detailed several strategies and options for managing the mental aspect of skin disorders in an article in the June issue of Seminars in Cutaneous Medicine and Surgery.

"Clinical studies have demonstrated that psychological stress disrupts skin barrier function and increases the severity of cutaneous infections, and down-regulates antimicrobial peptide expression, resulting in more severe skin infections in mice," Dr. Fried wrote.

"This self-perpetuating negative interaction between stress and impaired skin function has been well-described and often underlies the so-called ‘vicious cycle’ that exists between skin and negative emotional states," he said.

Dr. Fried proposed three broad categories of ‘psychocutaneous’ patients. First, there are individuals with skin manifestations associated a psychiatric diagnosis such as depression, anxiety, or body dysmorphic disorder.

The second category includes patients with psych-derm conditions such as acne excoriée, neurotic excoriations, dermatitis artefacta, and trichotillomania. The third category covers patients with common skin conditions such as acne, rosacea, psoriasis, eczema, and urticaria that are known to be impacted by emotional factors.

Dr. Fried suggested that even patients dealing with the dermatologic effects of aging may be at risk for negative emotional sequelae and may benefit from nonpharmacologic interventions.

Hypnosis is one intervention that has been shown to benefit some patients. For example, long-lasting effects of hypnosis (particularly in highly hypnotizable patients) may include reduced scratching in eczema, and can aid resolution of acne excoriée.

"Recent studies in patients with alopecia areata (including several with ophiasis distribution) demonstrated that hypnosis promotes excellent regrowth in approximately 50% of treated patients and improvements in depression and anxiety in almost all patients," Dr. Fried reported.

Cognitive-behavioral psychotherapy is one of several common psychotherapy interventions used to treat the psychological aspects of skin disorders. Data from a 6-week study of cognitive-behavioral therapy in psoriasis patients showed improvements in anxiety, depression, and psoriasis-related stress, compared with patients who didn’t receive the therapy. In addition, the psychotherapy intervention group showed three times the clinical improvement, compared those undergoing conventional treatment without therapy.

Group psychotherapy has also been associated with symptom reduction, decreased pruritus, fewer eczema relapses, and decreased steroid use in patients with eczema who used it to supplement to their regular medication.

But nonpharmacologic interventions can also be practiced in a less formal manner by dermatologists themselves, Dr. Fried said.

"The power to heal by words, manner, and touch cannot be overstated. Gentle, compassionate, and optimistic comments and gestures can affect the physiology, emotional well-being, and compliance of our patients," he said.

Dr. Fried said referral to a psychodermatologist or mental health professional with an interest in dermatologic manifestations may help some patients, but sometimes treatment can be as simple as a patient’s regular dermatologist offering reassuring words to, "assuage some of the ‘terror of chronicity and progression’ that haunts our patients," he said.

Dr. Fried stated that he has received compensation for the development of educational papers from Ranbaxy, Bayer, Valeant, and Promius.

sknews@frontlinemedcom.com

Nonpharmacologic interventions such as psychotherapy, hypnosis, and meditation can offer significant benefits to patients with dermatologic conditions including psoriasis, eczema, and urticaria, according to Dr. Richard G. Fried.

While the use of nonpharmacologic interventions may seem counterintuitive, these therapies have been shown to improve psychosocial function and reduce the negative emotional states that can exacerbate or even elicit skin disease, said Dr. Fried of Yardley (Pa.) Dermatology Associates. Dr. Fried detailed several strategies and options for managing the mental aspect of skin disorders in an article in the June issue of Seminars in Cutaneous Medicine and Surgery.

"Clinical studies have demonstrated that psychological stress disrupts skin barrier function and increases the severity of cutaneous infections, and down-regulates antimicrobial peptide expression, resulting in more severe skin infections in mice," Dr. Fried wrote.

"This self-perpetuating negative interaction between stress and impaired skin function has been well-described and often underlies the so-called ‘vicious cycle’ that exists between skin and negative emotional states," he said.

Dr. Fried proposed three broad categories of ‘psychocutaneous’ patients. First, there are individuals with skin manifestations associated a psychiatric diagnosis such as depression, anxiety, or body dysmorphic disorder.

The second category includes patients with psych-derm conditions such as acne excoriée, neurotic excoriations, dermatitis artefacta, and trichotillomania. The third category covers patients with common skin conditions such as acne, rosacea, psoriasis, eczema, and urticaria that are known to be impacted by emotional factors.

Dr. Fried suggested that even patients dealing with the dermatologic effects of aging may be at risk for negative emotional sequelae and may benefit from nonpharmacologic interventions.

Hypnosis is one intervention that has been shown to benefit some patients. For example, long-lasting effects of hypnosis (particularly in highly hypnotizable patients) may include reduced scratching in eczema, and can aid resolution of acne excoriée.

"Recent studies in patients with alopecia areata (including several with ophiasis distribution) demonstrated that hypnosis promotes excellent regrowth in approximately 50% of treated patients and improvements in depression and anxiety in almost all patients," Dr. Fried reported.

Cognitive-behavioral psychotherapy is one of several common psychotherapy interventions used to treat the psychological aspects of skin disorders. Data from a 6-week study of cognitive-behavioral therapy in psoriasis patients showed improvements in anxiety, depression, and psoriasis-related stress, compared with patients who didn’t receive the therapy. In addition, the psychotherapy intervention group showed three times the clinical improvement, compared those undergoing conventional treatment without therapy.

Group psychotherapy has also been associated with symptom reduction, decreased pruritus, fewer eczema relapses, and decreased steroid use in patients with eczema who used it to supplement to their regular medication.

But nonpharmacologic interventions can also be practiced in a less formal manner by dermatologists themselves, Dr. Fried said.

"The power to heal by words, manner, and touch cannot be overstated. Gentle, compassionate, and optimistic comments and gestures can affect the physiology, emotional well-being, and compliance of our patients," he said.

Dr. Fried said referral to a psychodermatologist or mental health professional with an interest in dermatologic manifestations may help some patients, but sometimes treatment can be as simple as a patient’s regular dermatologist offering reassuring words to, "assuage some of the ‘terror of chronicity and progression’ that haunts our patients," he said.

Dr. Fried stated that he has received compensation for the development of educational papers from Ranbaxy, Bayer, Valeant, and Promius.

sknews@frontlinemedcom.com

A review of the causes and impact of hospitalization in schizophrenia has shown that hospitalization is more likely the result of cognitive and functional decline rather than a contributor.

"While it is difficult to disentangle the consequence of the reasons for hospitalization from the effects of hospitalization, most contemporary hospitalizations are extremely brief, and the cause is typically psychotic exacerbation or aggressive and hostile behavior," wrote Philip D. Harvey, Ph.D., and his colleagues at the University of Miami.

"It is important to know whether being treated in a hospital, for either the short or long term, is an antecedent or consequence of clinical symptoms, cognitive deficits, and disability."

Historically, patients with schizophrenia were institutionalized in hospitals for long periods of time, but that changed with the introduction of chlorpromazine as treatment in the mid-1950s. This led to the discharge of a significant proportion of patients from long-stay care and changed the model of care for schizophrenia.

"Further, the entire inpatient treatment model for schizophrenia has changed drastically, from stays that averaged 6-12 weeks for "acute admissions" 25 years ago, to 5- to 7-day stays or even admissions that are not designated as admissions because the patient stays in the emergency room for up to 72 h," the authors reported (Neurobiol. Dis. 2013;53:18-25).

They concluded that while long hospital stays had the potential for adverse effects on functioning, there was an increased risk for medication nonadherence and psychotic relapses under the current model of care.

The review examined the ways in which hospitalization is used in schizophrenia, and how hospitalization relates to the course of the illness, assessment of patients, and general understanding of the disease.

Aggressive and disruptive behavior commonly precedes acute admission and can mean that patients are difficult to discharge even during times of high demand. Aggression is often predicted by deficits in frontal lobe function and is also associated with negative symptoms.

"Reducing aggression associated with cognitive deficits is challenging, because of the lack of interventions that target cognition and the possibility that cognitive functioning declines over time," the authors wrote.

The authors also identified recurrent or persistent psychosis as a risk factor for cortical deterioration and functional impairments, such as those seen in older institutionalized patients.

"Thus, these data suggest that continued efforts to engage people with schizophrenia in treatment can serve to prevent cognitive and functional declines associated with psychosis," the researchers wrote.

Clozapine treatment had been associated with a reduced risk of cortical degeneration and a reduction in psychosis among a subgroup of treatment-resistant patients, the authors said.

"Data to date [suggest] that these cognitive enhancement treatments are not effective on psychosis, so further developments in the treatment of nonadherent and treatment resistant patients seem required."

The review was partly supported by grants from the National Institute on Aging and National Institute of Mental Health. The authors did not declare any conflicts of interest.

A review of the causes and impact of hospitalization in schizophrenia has shown that hospitalization is more likely the result of cognitive and functional decline rather than a contributor.

"While it is difficult to disentangle the consequence of the reasons for hospitalization from the effects of hospitalization, most contemporary hospitalizations are extremely brief, and the cause is typically psychotic exacerbation or aggressive and hostile behavior," wrote Philip D. Harvey, Ph.D., and his colleagues at the University of Miami.

"It is important to know whether being treated in a hospital, for either the short or long term, is an antecedent or consequence of clinical symptoms, cognitive deficits, and disability."

Historically, patients with schizophrenia were institutionalized in hospitals for long periods of time, but that changed with the introduction of chlorpromazine as treatment in the mid-1950s. This led to the discharge of a significant proportion of patients from long-stay care and changed the model of care for schizophrenia.

"Further, the entire inpatient treatment model for schizophrenia has changed drastically, from stays that averaged 6-12 weeks for "acute admissions" 25 years ago, to 5- to 7-day stays or even admissions that are not designated as admissions because the patient stays in the emergency room for up to 72 h," the authors reported (Neurobiol. Dis. 2013;53:18-25).

They concluded that while long hospital stays had the potential for adverse effects on functioning, there was an increased risk for medication nonadherence and psychotic relapses under the current model of care.

The review examined the ways in which hospitalization is used in schizophrenia, and how hospitalization relates to the course of the illness, assessment of patients, and general understanding of the disease.

Aggressive and disruptive behavior commonly precedes acute admission and can mean that patients are difficult to discharge even during times of high demand. Aggression is often predicted by deficits in frontal lobe function and is also associated with negative symptoms.

"Reducing aggression associated with cognitive deficits is challenging, because of the lack of interventions that target cognition and the possibility that cognitive functioning declines over time," the authors wrote.

The authors also identified recurrent or persistent psychosis as a risk factor for cortical deterioration and functional impairments, such as those seen in older institutionalized patients.

"Thus, these data suggest that continued efforts to engage people with schizophrenia in treatment can serve to prevent cognitive and functional declines associated with psychosis," the researchers wrote.

Clozapine treatment had been associated with a reduced risk of cortical degeneration and a reduction in psychosis among a subgroup of treatment-resistant patients, the authors said.

"Data to date [suggest] that these cognitive enhancement treatments are not effective on psychosis, so further developments in the treatment of nonadherent and treatment resistant patients seem required."

The review was partly supported by grants from the National Institute on Aging and National Institute of Mental Health. The authors did not declare any conflicts of interest.

A review of the causes and impact of hospitalization in schizophrenia has shown that hospitalization is more likely the result of cognitive and functional decline rather than a contributor.

"While it is difficult to disentangle the consequence of the reasons for hospitalization from the effects of hospitalization, most contemporary hospitalizations are extremely brief, and the cause is typically psychotic exacerbation or aggressive and hostile behavior," wrote Philip D. Harvey, Ph.D., and his colleagues at the University of Miami.

"It is important to know whether being treated in a hospital, for either the short or long term, is an antecedent or consequence of clinical symptoms, cognitive deficits, and disability."

Historically, patients with schizophrenia were institutionalized in hospitals for long periods of time, but that changed with the introduction of chlorpromazine as treatment in the mid-1950s. This led to the discharge of a significant proportion of patients from long-stay care and changed the model of care for schizophrenia.

"Further, the entire inpatient treatment model for schizophrenia has changed drastically, from stays that averaged 6-12 weeks for "acute admissions" 25 years ago, to 5- to 7-day stays or even admissions that are not designated as admissions because the patient stays in the emergency room for up to 72 h," the authors reported (Neurobiol. Dis. 2013;53:18-25).

They concluded that while long hospital stays had the potential for adverse effects on functioning, there was an increased risk for medication nonadherence and psychotic relapses under the current model of care.

The review examined the ways in which hospitalization is used in schizophrenia, and how hospitalization relates to the course of the illness, assessment of patients, and general understanding of the disease.

Aggressive and disruptive behavior commonly precedes acute admission and can mean that patients are difficult to discharge even during times of high demand. Aggression is often predicted by deficits in frontal lobe function and is also associated with negative symptoms.

"Reducing aggression associated with cognitive deficits is challenging, because of the lack of interventions that target cognition and the possibility that cognitive functioning declines over time," the authors wrote.

The authors also identified recurrent or persistent psychosis as a risk factor for cortical deterioration and functional impairments, such as those seen in older institutionalized patients.

"Thus, these data suggest that continued efforts to engage people with schizophrenia in treatment can serve to prevent cognitive and functional declines associated with psychosis," the researchers wrote.

Clozapine treatment had been associated with a reduced risk of cortical degeneration and a reduction in psychosis among a subgroup of treatment-resistant patients, the authors said.

"Data to date [suggest] that these cognitive enhancement treatments are not effective on psychosis, so further developments in the treatment of nonadherent and treatment resistant patients seem required."

The review was partly supported by grants from the National Institute on Aging and National Institute of Mental Health. The authors did not declare any conflicts of interest.

Obesity was associated with an increased risk of precursor lesions among men with an initial benign prostate biopsy result, according to a nested study of nearly 500 prostate cancer cases and matched cancer-free controls.

Further, obese men also were more likely to have benign findings on initial core needle biopsy or transurethral resection of the prostate (TURP) and to then go on to develop prostate cancer within 4 years after their procedure.

"This is one of the first studies to assess associations between obesity and PIN (prostatic intraepithelial neoplasia)," reported Dr. Andrew Rundle of Columbia University, New York, and colleagues. The research was published in the April 23 online issue of Cancer Epidemiology, Biomarkers & Prevention (doi: 10.1158/1055-9965.EPI-12-0965). With approximately 1 million prostate biopsies conducted annually in the United States – two-thirds of which return negative results – obesity may be a factor to consider in the follow-up of individuals after an initial benign procedure.

In the study, obese men were more than twice as likely to have PIN detected in their initial benign specimens (OR = 2.17; 95% CI 1.13–4.15).

After adjustment for factors such as family history and prostate-specific antigen (PSA) levels, obesity at the time of the initial procedure was also associated with a significant increase in the incidence of prostate cancer, but only within 1,538 days of the initial procedure, which was the median duration of follow-up (OR = 1.95; 95% CI, 1.09-3.48).

Overall, a higher PSA value at the initial procedure and a family history of prostate cancer were associated with prostate cancer incidence, as was the number of PSA tests performed during follow-up. The association between obesity and prostate cancer incidence was confined to diagnoses occurring within less than 1,538 days, which was the median duration of follow-up after the initial benign procedure.

The findings emerged from a study that recruited 494 prostate cancer cases and matched cancer-free controls from a historical cohort of nearly 6,700 men followed up after a needle core biopsy or TURP. All had a benign prostate specimen collected between January 1990 and December 2002 and were followed up to December 2007 at the Henry Ford Health System in Detroit. The incidence of prostate cancer within this high-risk cohort was approximately twice that of the general Detroit Surveillance Epidemiology and End Results (SEER) population, although the ratio of African American to white cases in the cohort was similar to that in the overall SEER data.

All subjects had a recorded PSA level within a year of their initial benign procedure cohort entry and no history of a previous prostate cancer diagnosis. Patients diagnosed with prostate cancer less than 1 year from the date of their initial benign procedure were ineligible for the study. Controls were randomly selected from among those cohort members who were free of prostate cancer at a follow-up duration greater than or equal to the time between cohort entry and diagnosis of the matched case.

Body mass index was calculated from medical record data on height and weight measured within 115 days of the benign procedure. Overweight was a BMI of more than 25 and less than 30 and obese was a BMI of 30 or more. Surgical specimens were reviewed for the presence of PIN by a single urological pathologist who was blinded to prostate cancer outcomes at the time of review. Advanced stage disease was defined as pathologic or clinical stage T3a and higher.

In this study, in contrast to earlier cohort studies, obesity was not associated with high Gleason grade tumors, and obesity seemed to be more likely to be associated with low-grade tumors. "If the missed tumors were small and low grade, then they may have still been of lower grade when diagnosed in the first few years after the initial biopsy with high-grade prostate cancer and unassociated with or perhaps even protective for localized or low-grade disease," the researchers reported.

Obesity has been thought to reduce the sensitivity of PSA testing and, thus, may delay referral for biopsy. Obesity may also reduce the diagnostic efficiency of needle biopsies, as obese men have larger prostates and small tumors may be more likely to go undetected until they grow and are detected in subsequent biopsies during follow-up, the authors wrote.

The study was supported by a grant from the National Institute of Environmental Health Sciences, and the authors did not declare any potential conflicts of interest.

Obesity was associated with an increased risk of precursor lesions among men with an initial benign prostate biopsy result, according to a nested study of nearly 500 prostate cancer cases and matched cancer-free controls.

Further, obese men also were more likely to have benign findings on initial core needle biopsy or transurethral resection of the prostate (TURP) and to then go on to develop prostate cancer within 4 years after their procedure.

"This is one of the first studies to assess associations between obesity and PIN (prostatic intraepithelial neoplasia)," reported Dr. Andrew Rundle of Columbia University, New York, and colleagues. The research was published in the April 23 online issue of Cancer Epidemiology, Biomarkers & Prevention (doi: 10.1158/1055-9965.EPI-12-0965). With approximately 1 million prostate biopsies conducted annually in the United States – two-thirds of which return negative results – obesity may be a factor to consider in the follow-up of individuals after an initial benign procedure.

In the study, obese men were more than twice as likely to have PIN detected in their initial benign specimens (OR = 2.17; 95% CI 1.13–4.15).

After adjustment for factors such as family history and prostate-specific antigen (PSA) levels, obesity at the time of the initial procedure was also associated with a significant increase in the incidence of prostate cancer, but only within 1,538 days of the initial procedure, which was the median duration of follow-up (OR = 1.95; 95% CI, 1.09-3.48).

Overall, a higher PSA value at the initial procedure and a family history of prostate cancer were associated with prostate cancer incidence, as was the number of PSA tests performed during follow-up. The association between obesity and prostate cancer incidence was confined to diagnoses occurring within less than 1,538 days, which was the median duration of follow-up after the initial benign procedure.

The findings emerged from a study that recruited 494 prostate cancer cases and matched cancer-free controls from a historical cohort of nearly 6,700 men followed up after a needle core biopsy or TURP. All had a benign prostate specimen collected between January 1990 and December 2002 and were followed up to December 2007 at the Henry Ford Health System in Detroit. The incidence of prostate cancer within this high-risk cohort was approximately twice that of the general Detroit Surveillance Epidemiology and End Results (SEER) population, although the ratio of African American to white cases in the cohort was similar to that in the overall SEER data.

All subjects had a recorded PSA level within a year of their initial benign procedure cohort entry and no history of a previous prostate cancer diagnosis. Patients diagnosed with prostate cancer less than 1 year from the date of their initial benign procedure were ineligible for the study. Controls were randomly selected from among those cohort members who were free of prostate cancer at a follow-up duration greater than or equal to the time between cohort entry and diagnosis of the matched case.

Body mass index was calculated from medical record data on height and weight measured within 115 days of the benign procedure. Overweight was a BMI of more than 25 and less than 30 and obese was a BMI of 30 or more. Surgical specimens were reviewed for the presence of PIN by a single urological pathologist who was blinded to prostate cancer outcomes at the time of review. Advanced stage disease was defined as pathologic or clinical stage T3a and higher.

In this study, in contrast to earlier cohort studies, obesity was not associated with high Gleason grade tumors, and obesity seemed to be more likely to be associated with low-grade tumors. "If the missed tumors were small and low grade, then they may have still been of lower grade when diagnosed in the first few years after the initial biopsy with high-grade prostate cancer and unassociated with or perhaps even protective for localized or low-grade disease," the researchers reported.

Obesity has been thought to reduce the sensitivity of PSA testing and, thus, may delay referral for biopsy. Obesity may also reduce the diagnostic efficiency of needle biopsies, as obese men have larger prostates and small tumors may be more likely to go undetected until they grow and are detected in subsequent biopsies during follow-up, the authors wrote.

The study was supported by a grant from the National Institute of Environmental Health Sciences, and the authors did not declare any potential conflicts of interest.

Obesity was associated with an increased risk of precursor lesions among men with an initial benign prostate biopsy result, according to a nested study of nearly 500 prostate cancer cases and matched cancer-free controls.

Further, obese men also were more likely to have benign findings on initial core needle biopsy or transurethral resection of the prostate (TURP) and to then go on to develop prostate cancer within 4 years after their procedure.

"This is one of the first studies to assess associations between obesity and PIN (prostatic intraepithelial neoplasia)," reported Dr. Andrew Rundle of Columbia University, New York, and colleagues. The research was published in the April 23 online issue of Cancer Epidemiology, Biomarkers & Prevention (doi: 10.1158/1055-9965.EPI-12-0965). With approximately 1 million prostate biopsies conducted annually in the United States – two-thirds of which return negative results – obesity may be a factor to consider in the follow-up of individuals after an initial benign procedure.

In the study, obese men were more than twice as likely to have PIN detected in their initial benign specimens (OR = 2.17; 95% CI 1.13–4.15).

After adjustment for factors such as family history and prostate-specific antigen (PSA) levels, obesity at the time of the initial procedure was also associated with a significant increase in the incidence of prostate cancer, but only within 1,538 days of the initial procedure, which was the median duration of follow-up (OR = 1.95; 95% CI, 1.09-3.48).

Overall, a higher PSA value at the initial procedure and a family history of prostate cancer were associated with prostate cancer incidence, as was the number of PSA tests performed during follow-up. The association between obesity and prostate cancer incidence was confined to diagnoses occurring within less than 1,538 days, which was the median duration of follow-up after the initial benign procedure.

The findings emerged from a study that recruited 494 prostate cancer cases and matched cancer-free controls from a historical cohort of nearly 6,700 men followed up after a needle core biopsy or TURP. All had a benign prostate specimen collected between January 1990 and December 2002 and were followed up to December 2007 at the Henry Ford Health System in Detroit. The incidence of prostate cancer within this high-risk cohort was approximately twice that of the general Detroit Surveillance Epidemiology and End Results (SEER) population, although the ratio of African American to white cases in the cohort was similar to that in the overall SEER data.

All subjects had a recorded PSA level within a year of their initial benign procedure cohort entry and no history of a previous prostate cancer diagnosis. Patients diagnosed with prostate cancer less than 1 year from the date of their initial benign procedure were ineligible for the study. Controls were randomly selected from among those cohort members who were free of prostate cancer at a follow-up duration greater than or equal to the time between cohort entry and diagnosis of the matched case.

Body mass index was calculated from medical record data on height and weight measured within 115 days of the benign procedure. Overweight was a BMI of more than 25 and less than 30 and obese was a BMI of 30 or more. Surgical specimens were reviewed for the presence of PIN by a single urological pathologist who was blinded to prostate cancer outcomes at the time of review. Advanced stage disease was defined as pathologic or clinical stage T3a and higher.

In this study, in contrast to earlier cohort studies, obesity was not associated with high Gleason grade tumors, and obesity seemed to be more likely to be associated with low-grade tumors. "If the missed tumors were small and low grade, then they may have still been of lower grade when diagnosed in the first few years after the initial biopsy with high-grade prostate cancer and unassociated with or perhaps even protective for localized or low-grade disease," the researchers reported.

Obesity has been thought to reduce the sensitivity of PSA testing and, thus, may delay referral for biopsy. Obesity may also reduce the diagnostic efficiency of needle biopsies, as obese men have larger prostates and small tumors may be more likely to go undetected until they grow and are detected in subsequent biopsies during follow-up, the authors wrote.

The study was supported by a grant from the National Institute of Environmental Health Sciences, and the authors did not declare any potential conflicts of interest.

Adherence therapy improves symptoms in patients with schizophrenia but does not appear to affect adherence, treatment attitudes. or functioning, according to results of a randomized controlled trial.

"We observed a small effect of AT [adherence therapy] on patient symptoms but not adherence, treatment attitudes, or functioning following an acute episode of schizophrenia," wrote Dr. Michael Schulz of the University of Applied Sciences, Bielefeld, Germany, and his colleagues. "It was disappointing that we found no evidence to support our proposed mechanism of action for AT; there was no evidence of an effect of the intervention on either patients’ beliefs or adherence."

The parallel-group trial involved 161 patients admitted for treatment of an acute exacerbation of schizophrenia – 123 of whom finished the trial – and randomized patients to receive either eight sessions of adherence therapy or treatment as usual (Schizophr. Res. 2013;146:59-63).

Outcomes were assessed with the positive and negative syndrome scale (PANSS) and serum concentration to dose ratio, with researchers suggesting this was the first such trial to use a biological marker to measure adherence.

The adherence therapy consisted of eight one-on-one sessions with a trained therapist, designed to explore, assess, and test patients’ history, experience, and beliefs about medication and treatment. Treatment as usual followed national guidelines.

Previous studies of adherence therapy had produced mixed results, although trials that intervened just after an acute episode generally had more positive outcomes.

"We hypothesized that AT initiated whilst patients with schizophrenia are inpatient and followed up in the community will be effective in enhancing adherence and reducing psychopathology compared to usual care," the researchers wrote.

The authors suggested that the lack of clear benefit in adherence or patient beliefs pointed to a "ceiling effect," particularly as there was likely a sample bias toward more compliant patients with almost half the patients eligible for recruitment to the trial either refusing to take part or being excluded.

"A major problem in conducting adherence trials in severe mental illness is recruiting nonadherent patients," the researchers reported. "Both AT and TAU [treatment as usual] groups were not only adherent to treatment, which might be expected in inpatients following an acute episode, but also had positive medication attitudes. This may explain why AT has so little effect on patients’ beliefs, i.e. there may be a ceiling effect limiting the possible impact AT could have."

Despite the failure of this and previous trials to demonstrate clear benefits of adherence therapy on patient adherence and beliefs, the authors said the approach was still "theoretically sound."

"The findings from this trial would lend weight to the argument that intervening as soon as possible after an acute episode of illness in patients with schizophrenia affords the best chance to effect change," they wrote.

"Perhaps one of the most important challenges in adherence research is the recruitment of patients who are treatment non-compliant."

The study was supported by AstraZeneca, and one author declared honoraria and consultancies to a range of pharmaceutical companies, including AstraZeneca.

Adherence therapy improves symptoms in patients with schizophrenia but does not appear to affect adherence, treatment attitudes. or functioning, according to results of a randomized controlled trial.

"We observed a small effect of AT [adherence therapy] on patient symptoms but not adherence, treatment attitudes, or functioning following an acute episode of schizophrenia," wrote Dr. Michael Schulz of the University of Applied Sciences, Bielefeld, Germany, and his colleagues. "It was disappointing that we found no evidence to support our proposed mechanism of action for AT; there was no evidence of an effect of the intervention on either patients’ beliefs or adherence."

The parallel-group trial involved 161 patients admitted for treatment of an acute exacerbation of schizophrenia – 123 of whom finished the trial – and randomized patients to receive either eight sessions of adherence therapy or treatment as usual (Schizophr. Res. 2013;146:59-63).

Outcomes were assessed with the positive and negative syndrome scale (PANSS) and serum concentration to dose ratio, with researchers suggesting this was the first such trial to use a biological marker to measure adherence.

The adherence therapy consisted of eight one-on-one sessions with a trained therapist, designed to explore, assess, and test patients’ history, experience, and beliefs about medication and treatment. Treatment as usual followed national guidelines.

Previous studies of adherence therapy had produced mixed results, although trials that intervened just after an acute episode generally had more positive outcomes.

"We hypothesized that AT initiated whilst patients with schizophrenia are inpatient and followed up in the community will be effective in enhancing adherence and reducing psychopathology compared to usual care," the researchers wrote.

The authors suggested that the lack of clear benefit in adherence or patient beliefs pointed to a "ceiling effect," particularly as there was likely a sample bias toward more compliant patients with almost half the patients eligible for recruitment to the trial either refusing to take part or being excluded.

"A major problem in conducting adherence trials in severe mental illness is recruiting nonadherent patients," the researchers reported. "Both AT and TAU [treatment as usual] groups were not only adherent to treatment, which might be expected in inpatients following an acute episode, but also had positive medication attitudes. This may explain why AT has so little effect on patients’ beliefs, i.e. there may be a ceiling effect limiting the possible impact AT could have."

Despite the failure of this and previous trials to demonstrate clear benefits of adherence therapy on patient adherence and beliefs, the authors said the approach was still "theoretically sound."

"The findings from this trial would lend weight to the argument that intervening as soon as possible after an acute episode of illness in patients with schizophrenia affords the best chance to effect change," they wrote.

"Perhaps one of the most important challenges in adherence research is the recruitment of patients who are treatment non-compliant."

The study was supported by AstraZeneca, and one author declared honoraria and consultancies to a range of pharmaceutical companies, including AstraZeneca.

Adherence therapy improves symptoms in patients with schizophrenia but does not appear to affect adherence, treatment attitudes. or functioning, according to results of a randomized controlled trial.

"We observed a small effect of AT [adherence therapy] on patient symptoms but not adherence, treatment attitudes, or functioning following an acute episode of schizophrenia," wrote Dr. Michael Schulz of the University of Applied Sciences, Bielefeld, Germany, and his colleagues. "It was disappointing that we found no evidence to support our proposed mechanism of action for AT; there was no evidence of an effect of the intervention on either patients’ beliefs or adherence."

The parallel-group trial involved 161 patients admitted for treatment of an acute exacerbation of schizophrenia – 123 of whom finished the trial – and randomized patients to receive either eight sessions of adherence therapy or treatment as usual (Schizophr. Res. 2013;146:59-63).

Outcomes were assessed with the positive and negative syndrome scale (PANSS) and serum concentration to dose ratio, with researchers suggesting this was the first such trial to use a biological marker to measure adherence.

The adherence therapy consisted of eight one-on-one sessions with a trained therapist, designed to explore, assess, and test patients’ history, experience, and beliefs about medication and treatment. Treatment as usual followed national guidelines.

Previous studies of adherence therapy had produced mixed results, although trials that intervened just after an acute episode generally had more positive outcomes.

"We hypothesized that AT initiated whilst patients with schizophrenia are inpatient and followed up in the community will be effective in enhancing adherence and reducing psychopathology compared to usual care," the researchers wrote.

The authors suggested that the lack of clear benefit in adherence or patient beliefs pointed to a "ceiling effect," particularly as there was likely a sample bias toward more compliant patients with almost half the patients eligible for recruitment to the trial either refusing to take part or being excluded.

"A major problem in conducting adherence trials in severe mental illness is recruiting nonadherent patients," the researchers reported. "Both AT and TAU [treatment as usual] groups were not only adherent to treatment, which might be expected in inpatients following an acute episode, but also had positive medication attitudes. This may explain why AT has so little effect on patients’ beliefs, i.e. there may be a ceiling effect limiting the possible impact AT could have."

Despite the failure of this and previous trials to demonstrate clear benefits of adherence therapy on patient adherence and beliefs, the authors said the approach was still "theoretically sound."

"The findings from this trial would lend weight to the argument that intervening as soon as possible after an acute episode of illness in patients with schizophrenia affords the best chance to effect change," they wrote.

"Perhaps one of the most important challenges in adherence research is the recruitment of patients who are treatment non-compliant."

The study was supported by AstraZeneca, and one author declared honoraria and consultancies to a range of pharmaceutical companies, including AstraZeneca.

The antiarrhythmic drug amiodarone is associated with an increased risk of cancer, but the effect is significant only in men or at higher doses, according to a Taiwanese population-based cohort study published online April 8 in Cancer.

"We found that there was a borderline significantly increased risk of cancer among patients who received amiodarone compared with the general population," wrote Dr. Vincent Yi-Fong Su of the Taipei (Taiwan) Veterans General Hospital and his colleagues. Patients either of male sex or with more than 180 cumulative defined daily doses within the first year "had a significantly higher risk of developing cancer, and those with both factors had an even greater SIR [standardized incidence ratio] of 1.46 (P = .008)."

Amiodarone can build up in the soft tissues and increase the risk of lung masses, thyroid cancer, and skin cancer.

While all patients receiving amiodarone had a slight increase in their overall risk of cancer (SIR, 1.12; 95% CI, 0.99-1.26; P = .067), the risk was significantly higher in men (SIR, 1.18; 95% CI, 1.02-1.36; P = .022) but not in women (SIR, 0.99; 95% CI, 0.79-1.23).

"One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat," the authors reported.

The study also found a dose-dependent relationship between amiodarone and cancer risk. Among patients in the middle and top tertile of cumulative defined daily dose, the adjusted hazard ratios were 1.70 (95% CI, 1.02-2.84; P = .042) and 1.98 (95% CI, 1.22-3.22; P = .006) respectively, after adjustment for age, sex, and comorbidities.

The researchers examined data from 6,418 patients treated with amiodarone, 43% of whom were female, using information from the Taiwan National Health Insurance Research Database.

During the median 2.6-year follow-up, 280 patients developed cancer, with no significant differences found in the type or location of cancer. Amiodarone, approved by the Food and Drug Administration in 1985, is a fat-soluble drug with a long elimination half-life, so large amounts of the drug can build up in the soft tissues after prolonged treatment, and postmarketing surveillance had suggested an increased risk of lung masses, thyroid cancer, and skin cancer.

The researchers noted an increase in the incidence of cancer in the first year after amiodarone therapy (SIR, 1.32; 95% CI, 1.05-1.64; P = .002), although they suggested this may be due to surveillance bias (Cancer 2013 April 8 2013 [doi.wiley.com/10.1002/cncr.27881].

"To provide an initial, thorough evaluation of the etiology of arrhythmias and to monitor the toxicity of amiodarone in follow-up studies, an increased number of medical examinations are performed in patients treated with amiodarone," the authors wrote. "Thus, the cancer incidence within the first year falsely increases due to early detection."

While the study excluded patients with preexisting malignancies, researchers were not able to account for other risk factors, such as obesity, smoking and alcohol use, environmental exposure, and family history of cancer.

The authors concluded that while extensive screening for occult cancers in patients taking amiodarone was not practical, they advocated closer surveillance of cancer events in future amiodarone trials.

The study was partly supported by the Taipei (Taiwan) Veterans General Hospital. The authors reported no relevant financial conflicts.

The antiarrhythmic drug amiodarone is associated with an increased risk of cancer, but the effect is significant only in men or at higher doses, according to a Taiwanese population-based cohort study published online April 8 in Cancer.

"We found that there was a borderline significantly increased risk of cancer among patients who received amiodarone compared with the general population," wrote Dr. Vincent Yi-Fong Su of the Taipei (Taiwan) Veterans General Hospital and his colleagues. Patients either of male sex or with more than 180 cumulative defined daily doses within the first year "had a significantly higher risk of developing cancer, and those with both factors had an even greater SIR [standardized incidence ratio] of 1.46 (P = .008)."

Amiodarone can build up in the soft tissues and increase the risk of lung masses, thyroid cancer, and skin cancer.

While all patients receiving amiodarone had a slight increase in their overall risk of cancer (SIR, 1.12; 95% CI, 0.99-1.26; P = .067), the risk was significantly higher in men (SIR, 1.18; 95% CI, 1.02-1.36; P = .022) but not in women (SIR, 0.99; 95% CI, 0.79-1.23).

"One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat," the authors reported.

The study also found a dose-dependent relationship between amiodarone and cancer risk. Among patients in the middle and top tertile of cumulative defined daily dose, the adjusted hazard ratios were 1.70 (95% CI, 1.02-2.84; P = .042) and 1.98 (95% CI, 1.22-3.22; P = .006) respectively, after adjustment for age, sex, and comorbidities.

The researchers examined data from 6,418 patients treated with amiodarone, 43% of whom were female, using information from the Taiwan National Health Insurance Research Database.

During the median 2.6-year follow-up, 280 patients developed cancer, with no significant differences found in the type or location of cancer. Amiodarone, approved by the Food and Drug Administration in 1985, is a fat-soluble drug with a long elimination half-life, so large amounts of the drug can build up in the soft tissues after prolonged treatment, and postmarketing surveillance had suggested an increased risk of lung masses, thyroid cancer, and skin cancer.

The researchers noted an increase in the incidence of cancer in the first year after amiodarone therapy (SIR, 1.32; 95% CI, 1.05-1.64; P = .002), although they suggested this may be due to surveillance bias (Cancer 2013 April 8 2013 [doi.wiley.com/10.1002/cncr.27881].

"To provide an initial, thorough evaluation of the etiology of arrhythmias and to monitor the toxicity of amiodarone in follow-up studies, an increased number of medical examinations are performed in patients treated with amiodarone," the authors wrote. "Thus, the cancer incidence within the first year falsely increases due to early detection."

While the study excluded patients with preexisting malignancies, researchers were not able to account for other risk factors, such as obesity, smoking and alcohol use, environmental exposure, and family history of cancer.

The authors concluded that while extensive screening for occult cancers in patients taking amiodarone was not practical, they advocated closer surveillance of cancer events in future amiodarone trials.

The study was partly supported by the Taipei (Taiwan) Veterans General Hospital. The authors reported no relevant financial conflicts.

The antiarrhythmic drug amiodarone is associated with an increased risk of cancer, but the effect is significant only in men or at higher doses, according to a Taiwanese population-based cohort study published online April 8 in Cancer.

"We found that there was a borderline significantly increased risk of cancer among patients who received amiodarone compared with the general population," wrote Dr. Vincent Yi-Fong Su of the Taipei (Taiwan) Veterans General Hospital and his colleagues. Patients either of male sex or with more than 180 cumulative defined daily doses within the first year "had a significantly higher risk of developing cancer, and those with both factors had an even greater SIR [standardized incidence ratio] of 1.46 (P = .008)."

Amiodarone can build up in the soft tissues and increase the risk of lung masses, thyroid cancer, and skin cancer.

While all patients receiving amiodarone had a slight increase in their overall risk of cancer (SIR, 1.12; 95% CI, 0.99-1.26; P = .067), the risk was significantly higher in men (SIR, 1.18; 95% CI, 1.02-1.36; P = .022) but not in women (SIR, 0.99; 95% CI, 0.79-1.23).

"One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat," the authors reported.

The study also found a dose-dependent relationship between amiodarone and cancer risk. Among patients in the middle and top tertile of cumulative defined daily dose, the adjusted hazard ratios were 1.70 (95% CI, 1.02-2.84; P = .042) and 1.98 (95% CI, 1.22-3.22; P = .006) respectively, after adjustment for age, sex, and comorbidities.

The researchers examined data from 6,418 patients treated with amiodarone, 43% of whom were female, using information from the Taiwan National Health Insurance Research Database.

During the median 2.6-year follow-up, 280 patients developed cancer, with no significant differences found in the type or location of cancer. Amiodarone, approved by the Food and Drug Administration in 1985, is a fat-soluble drug with a long elimination half-life, so large amounts of the drug can build up in the soft tissues after prolonged treatment, and postmarketing surveillance had suggested an increased risk of lung masses, thyroid cancer, and skin cancer.

The researchers noted an increase in the incidence of cancer in the first year after amiodarone therapy (SIR, 1.32; 95% CI, 1.05-1.64; P = .002), although they suggested this may be due to surveillance bias (Cancer 2013 April 8 2013 [doi.wiley.com/10.1002/cncr.27881].

"To provide an initial, thorough evaluation of the etiology of arrhythmias and to monitor the toxicity of amiodarone in follow-up studies, an increased number of medical examinations are performed in patients treated with amiodarone," the authors wrote. "Thus, the cancer incidence within the first year falsely increases due to early detection."

While the study excluded patients with preexisting malignancies, researchers were not able to account for other risk factors, such as obesity, smoking and alcohol use, environmental exposure, and family history of cancer.

The authors concluded that while extensive screening for occult cancers in patients taking amiodarone was not practical, they advocated closer surveillance of cancer events in future amiodarone trials.

The study was partly supported by the Taipei (Taiwan) Veterans General Hospital. The authors reported no relevant financial conflicts.

Folate and vitamin B₁₂ supplements may improve the negative symptoms of schizophrenia but only in patients with a genetic variant that influences folate metabolism, a study has shown.

"Although four such variants have previously been associated with negative symptom severity, the genotype that contributed most strongly to treatment response was FOLH1 484T>C," wrote Dr. Joshua L. Roffman, of the psychiatry department at Massachusetts General Hospital, Boston, and his colleagues.

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Patients treated with folate plus vitamin B₁₂ showed significant improvement on the Scale for the Assessment of Negative Symptoms (SANS), compared with placebo (group difference, –0.33 change in score per week; 95% confidence interval, –0.62 to –0.05), when genotype was taken into account.

Among patients homozygous for the 484T allele – a genetic variant in the folate hydrolase 1 (FOLH1) gene – the benefits of folate and vitamin B₁₂ supplements were even greater (–0.59 change in SANS score per week; 95% CI, –0.99 to –0.18), according to results published in JAMA Psychiatry (formerly Archives of General Psychiatry) (2013 March 6 [doi: 10.1001/jamapsychiatry.2013.900]).

The double-blind, placebo-controlled study randomized 140 outpatients with schizophrenia, who had persistent symptoms despite treatment with antipsychotics, to 2 mg of folic acid and 400 mcg of vitamin B₁₂ daily for 16 weeks or placebo. The patients were 18-68 years old, had been treated with an antipsychotic for at least 6 months, and were at a stable dose for at least 6 weeks. They also had to have scored at least 60 on the Positive and Negative Syndrome Scale.

The study found that only the high-functioning variant of FOLH1 (484T) was associated with a benefit from supplementation, while the effects of supplementation did not reach significance for either the low-functioning variant of FOLH1 (484C) or the MTHFR, MTR, or COMT genotypes.

While the treatment effects were modest, the researchers noted that even small effects could be clinically meaningful given the disability associated with negative symptoms, the paucity of available treatments for these symptoms, and the minimal side effects of vitamin supplements.

Folate deficiency is known to be a risk factor for schizophrenia, and all four genetic variants included in the study have been associated with increased severity of negative symptoms such as apathy, social withdrawal, and loss of emotional expressiveness.

"Thus, the finding that only patients homozygous for the T allele exhibited improvement in negative symptoms after 16 weeks of folate supplementation could reflect diminished folate absorption, and briefer exposure to higher folate levels, among C allele carriers," the researchers wrote.

The authors suggested that the findings could have implications for other health conditions associated with reduced folate and elevated homocysteine concentrations, such as stroke, cardiovascular disease, and dementia. "The current results suggest that individual differences in folate metabolism related to the presence of common functional genetic variants may have a bearing on treatment outcomes in these other disorders, as well as negative symptoms of schizophrenia," Dr. Roffman and his colleagues noted.

The research was funded by the National Institute of Mental Health and an award from the Howard Hughes Medical Institute, with support from Harvard Catalyst. The investigators disclosed receiving support and grants from a number of pharmaceutical companies and research organizations.

Folate and vitamin B₁₂ supplements may improve the negative symptoms of schizophrenia but only in patients with a genetic variant that influences folate metabolism, a study has shown.

"Although four such variants have previously been associated with negative symptom severity, the genotype that contributed most strongly to treatment response was FOLH1 484T>C," wrote Dr. Joshua L. Roffman, of the psychiatry department at Massachusetts General Hospital, Boston, and his colleagues.

© thinkstockphotos.com

Patients treated with folate plus vitamin B₁₂ showed significant improvement on the Scale for the Assessment of Negative Symptoms (SANS), compared with placebo (group difference, –0.33 change in score per week; 95% confidence interval, –0.62 to –0.05), when genotype was taken into account.

Among patients homozygous for the 484T allele – a genetic variant in the folate hydrolase 1 (FOLH1) gene – the benefits of folate and vitamin B₁₂ supplements were even greater (–0.59 change in SANS score per week; 95% CI, –0.99 to –0.18), according to results published in JAMA Psychiatry (formerly Archives of General Psychiatry) (2013 March 6 [doi: 10.1001/jamapsychiatry.2013.900]).

The double-blind, placebo-controlled study randomized 140 outpatients with schizophrenia, who had persistent symptoms despite treatment with antipsychotics, to 2 mg of folic acid and 400 mcg of vitamin B₁₂ daily for 16 weeks or placebo. The patients were 18-68 years old, had been treated with an antipsychotic for at least 6 months, and were at a stable dose for at least 6 weeks. They also had to have scored at least 60 on the Positive and Negative Syndrome Scale.

The study found that only the high-functioning variant of FOLH1 (484T) was associated with a benefit from supplementation, while the effects of supplementation did not reach significance for either the low-functioning variant of FOLH1 (484C) or the MTHFR, MTR, or COMT genotypes.

While the treatment effects were modest, the researchers noted that even small effects could be clinically meaningful given the disability associated with negative symptoms, the paucity of available treatments for these symptoms, and the minimal side effects of vitamin supplements.

Folate deficiency is known to be a risk factor for schizophrenia, and all four genetic variants included in the study have been associated with increased severity of negative symptoms such as apathy, social withdrawal, and loss of emotional expressiveness.

"Thus, the finding that only patients homozygous for the T allele exhibited improvement in negative symptoms after 16 weeks of folate supplementation could reflect diminished folate absorption, and briefer exposure to higher folate levels, among C allele carriers," the researchers wrote.

The authors suggested that the findings could have implications for other health conditions associated with reduced folate and elevated homocysteine concentrations, such as stroke, cardiovascular disease, and dementia. "The current results suggest that individual differences in folate metabolism related to the presence of common functional genetic variants may have a bearing on treatment outcomes in these other disorders, as well as negative symptoms of schizophrenia," Dr. Roffman and his colleagues noted.

The research was funded by the National Institute of Mental Health and an award from the Howard Hughes Medical Institute, with support from Harvard Catalyst. The investigators disclosed receiving support and grants from a number of pharmaceutical companies and research organizations.

Folate and vitamin B₁₂ supplements may improve the negative symptoms of schizophrenia but only in patients with a genetic variant that influences folate metabolism, a study has shown.

"Although four such variants have previously been associated with negative symptom severity, the genotype that contributed most strongly to treatment response was FOLH1 484T>C," wrote Dr. Joshua L. Roffman, of the psychiatry department at Massachusetts General Hospital, Boston, and his colleagues.

© thinkstockphotos.com

Patients treated with folate plus vitamin B₁₂ showed significant improvement on the Scale for the Assessment of Negative Symptoms (SANS), compared with placebo (group difference, –0.33 change in score per week; 95% confidence interval, –0.62 to –0.05), when genotype was taken into account.

Among patients homozygous for the 484T allele – a genetic variant in the folate hydrolase 1 (FOLH1) gene – the benefits of folate and vitamin B₁₂ supplements were even greater (–0.59 change in SANS score per week; 95% CI, –0.99 to –0.18), according to results published in JAMA Psychiatry (formerly Archives of General Psychiatry) (2013 March 6 [doi: 10.1001/jamapsychiatry.2013.900]).

The double-blind, placebo-controlled study randomized 140 outpatients with schizophrenia, who had persistent symptoms despite treatment with antipsychotics, to 2 mg of folic acid and 400 mcg of vitamin B₁₂ daily for 16 weeks or placebo. The patients were 18-68 years old, had been treated with an antipsychotic for at least 6 months, and were at a stable dose for at least 6 weeks. They also had to have scored at least 60 on the Positive and Negative Syndrome Scale.

The study found that only the high-functioning variant of FOLH1 (484T) was associated with a benefit from supplementation, while the effects of supplementation did not reach significance for either the low-functioning variant of FOLH1 (484C) or the MTHFR, MTR, or COMT genotypes.

While the treatment effects were modest, the researchers noted that even small effects could be clinically meaningful given the disability associated with negative symptoms, the paucity of available treatments for these symptoms, and the minimal side effects of vitamin supplements.

Folate deficiency is known to be a risk factor for schizophrenia, and all four genetic variants included in the study have been associated with increased severity of negative symptoms such as apathy, social withdrawal, and loss of emotional expressiveness.

"Thus, the finding that only patients homozygous for the T allele exhibited improvement in negative symptoms after 16 weeks of folate supplementation could reflect diminished folate absorption, and briefer exposure to higher folate levels, among C allele carriers," the researchers wrote.

The authors suggested that the findings could have implications for other health conditions associated with reduced folate and elevated homocysteine concentrations, such as stroke, cardiovascular disease, and dementia. "The current results suggest that individual differences in folate metabolism related to the presence of common functional genetic variants may have a bearing on treatment outcomes in these other disorders, as well as negative symptoms of schizophrenia," Dr. Roffman and his colleagues noted.

The research was funded by the National Institute of Mental Health and an award from the Howard Hughes Medical Institute, with support from Harvard Catalyst. The investigators disclosed receiving support and grants from a number of pharmaceutical companies and research organizations.

The deficit subtype of schizophrenia is characterized by white matter tract disruption, while all subtypes of schizophrenia feature a reduction in cortical thickness, a cross-sectional neuroimaging study has found.

Patients with deficit schizophrenia showed significant disruption of white matter at the right inferior longitudinal fasciculus, the right arcuate fasciculus, and the left uncinate fasciculus, compared with nondeficit patients and healthy controls, according to a study published in the March 6 online issue of JAMA Psychiatry (doi:10.1001/jamapsychiatry.2013.786).

The study, which used high-resolution MRI to compare 77 patients with schizophrenia – 18 with deficit and 59 nondeficit – and 79 healthy controls, found these features also were present within first-episode patients who showed deficit-like characteristics. The main characteristics of the deficit subtype include primary, enduring negative symptoms and impaired emotion processing, emotion expression, and social function.

“Our finding within first-episode patients that a more ‘deficit-like’ clinical picture was associated with greater impairment within these same white matter tracts supports the fact that white matter disruption in these patients is a feature of the clinical deficit subtype, rather than other factors such as long-term medication exposure or duration of illness,” wrote Dr. Aristotle N. Voineskos of the Centre for Addiction and Mental Health, Toronto, and his colleagues.

“In contrast, we also found that cortical thickness reductions were present in the same regions in both deficit and nondeficit patients compared with healthy controls, which supports the consistency of cortical thickness findings in different clinical subtypes,” they noted.

The areas of white matter most significantly altered in deficit patients connect regions of the brain involved in the expression and processing of emotion and in socioemotional functioning – functions that are typically impaired in patients with deficit schizophrenia and are present from the first episode.

“The major impairments and low recovery rates of these patients make this group a high priority for investigation,” the researchers wrote. “Furthermore, studying this more clinically homogeneous subgroup may facilitate biomarker discovery which has been a challenge not only for schizophrenia but for psychiatry research as a whole.”

The finding of cortical thickness reductions in the same regions of the brain in both deficit and nondeficit subtype patients supports the idea that this is a characteristic clinical feature of schizophrenia, Dr. Voineskos and his associates said.

Although most of the patients included in the study had a long history of schizophrenia and a history of antipsychotic medication use, researchers also included patients with first-episode schizophrenia to account for age, illness duration, and effects of medication.

“These data were particularly helpful in light of recent, somewhat conflicting reports regarding the effects of these variables on cortical brain structure,” the researchers wrote.

Individual researchers were supported by the Canadian Institutes of Health, American Psychiatric Association/American Psychiatric Institute for Research and Education, the Brain and Behavior Research Foundation, the Ontario Mental Health Foundation, and the Centre for Addiction and Mental Health and the CAMH Foundation.

Dr. Voineskos had no disclosures. His coauthors disclosed various involvements with numerous pharmaceutical companies, including Forest Laboratories, Wyeth, Takeda, and Lundbeck Canada.

cpnews@frontlinemedcom.com

The deficit subtype of schizophrenia is characterized by white matter tract disruption, while all subtypes of schizophrenia feature a reduction in cortical thickness, a cross-sectional neuroimaging study has found.

Patients with deficit schizophrenia showed significant disruption of white matter at the right inferior longitudinal fasciculus, the right arcuate fasciculus, and the left uncinate fasciculus, compared with nondeficit patients and healthy controls, according to a study published in the March 6 online issue of JAMA Psychiatry (doi:10.1001/jamapsychiatry.2013.786).

The study, which used high-resolution MRI to compare 77 patients with schizophrenia – 18 with deficit and 59 nondeficit – and 79 healthy controls, found these features also were present within first-episode patients who showed deficit-like characteristics. The main characteristics of the deficit subtype include primary, enduring negative symptoms and impaired emotion processing, emotion expression, and social function.

“Our finding within first-episode patients that a more ‘deficit-like’ clinical picture was associated with greater impairment within these same white matter tracts supports the fact that white matter disruption in these patients is a feature of the clinical deficit subtype, rather than other factors such as long-term medication exposure or duration of illness,” wrote Dr. Aristotle N. Voineskos of the Centre for Addiction and Mental Health, Toronto, and his colleagues.

“In contrast, we also found that cortical thickness reductions were present in the same regions in both deficit and nondeficit patients compared with healthy controls, which supports the consistency of cortical thickness findings in different clinical subtypes,” they noted.

The areas of white matter most significantly altered in deficit patients connect regions of the brain involved in the expression and processing of emotion and in socioemotional functioning – functions that are typically impaired in patients with deficit schizophrenia and are present from the first episode.

“The major impairments and low recovery rates of these patients make this group a high priority for investigation,” the researchers wrote. “Furthermore, studying this more clinically homogeneous subgroup may facilitate biomarker discovery which has been a challenge not only for schizophrenia but for psychiatry research as a whole.”

The finding of cortical thickness reductions in the same regions of the brain in both deficit and nondeficit subtype patients supports the idea that this is a characteristic clinical feature of schizophrenia, Dr. Voineskos and his associates said.

Although most of the patients included in the study had a long history of schizophrenia and a history of antipsychotic medication use, researchers also included patients with first-episode schizophrenia to account for age, illness duration, and effects of medication.

“These data were particularly helpful in light of recent, somewhat conflicting reports regarding the effects of these variables on cortical brain structure,” the researchers wrote.

Individual researchers were supported by the Canadian Institutes of Health, American Psychiatric Association/American Psychiatric Institute for Research and Education, the Brain and Behavior Research Foundation, the Ontario Mental Health Foundation, and the Centre for Addiction and Mental Health and the CAMH Foundation.

Dr. Voineskos had no disclosures. His coauthors disclosed various involvements with numerous pharmaceutical companies, including Forest Laboratories, Wyeth, Takeda, and Lundbeck Canada.

cpnews@frontlinemedcom.com

The deficit subtype of schizophrenia is characterized by white matter tract disruption, while all subtypes of schizophrenia feature a reduction in cortical thickness, a cross-sectional neuroimaging study has found.

Patients with deficit schizophrenia showed significant disruption of white matter at the right inferior longitudinal fasciculus, the right arcuate fasciculus, and the left uncinate fasciculus, compared with nondeficit patients and healthy controls, according to a study published in the March 6 online issue of JAMA Psychiatry (doi:10.1001/jamapsychiatry.2013.786).

The study, which used high-resolution MRI to compare 77 patients with schizophrenia – 18 with deficit and 59 nondeficit – and 79 healthy controls, found these features also were present within first-episode patients who showed deficit-like characteristics. The main characteristics of the deficit subtype include primary, enduring negative symptoms and impaired emotion processing, emotion expression, and social function.

“Our finding within first-episode patients that a more ‘deficit-like’ clinical picture was associated with greater impairment within these same white matter tracts supports the fact that white matter disruption in these patients is a feature of the clinical deficit subtype, rather than other factors such as long-term medication exposure or duration of illness,” wrote Dr. Aristotle N. Voineskos of the Centre for Addiction and Mental Health, Toronto, and his colleagues.

“In contrast, we also found that cortical thickness reductions were present in the same regions in both deficit and nondeficit patients compared with healthy controls, which supports the consistency of cortical thickness findings in different clinical subtypes,” they noted.

The areas of white matter most significantly altered in deficit patients connect regions of the brain involved in the expression and processing of emotion and in socioemotional functioning – functions that are typically impaired in patients with deficit schizophrenia and are present from the first episode.

“The major impairments and low recovery rates of these patients make this group a high priority for investigation,” the researchers wrote. “Furthermore, studying this more clinically homogeneous subgroup may facilitate biomarker discovery which has been a challenge not only for schizophrenia but for psychiatry research as a whole.”

The finding of cortical thickness reductions in the same regions of the brain in both deficit and nondeficit subtype patients supports the idea that this is a characteristic clinical feature of schizophrenia, Dr. Voineskos and his associates said.

Although most of the patients included in the study had a long history of schizophrenia and a history of antipsychotic medication use, researchers also included patients with first-episode schizophrenia to account for age, illness duration, and effects of medication.

“These data were particularly helpful in light of recent, somewhat conflicting reports regarding the effects of these variables on cortical brain structure,” the researchers wrote.

Individual researchers were supported by the Canadian Institutes of Health, American Psychiatric Association/American Psychiatric Institute for Research and Education, the Brain and Behavior Research Foundation, the Ontario Mental Health Foundation, and the Centre for Addiction and Mental Health and the CAMH Foundation.

Dr. Voineskos had no disclosures. His coauthors disclosed various involvements with numerous pharmaceutical companies, including Forest Laboratories, Wyeth, Takeda, and Lundbeck Canada.

cpnews@frontlinemedcom.com

Gastric bypass leads to more significant and durable improvements in glycemic control than does sleeve gastrectomy or intensive medical therapy in moderately obese patients with type 2 diabetes, a prospective, randomized controlled trial has found.

Two years after the procedure, patients randomized to Roux-en-Y gastric bypass plus intensive medical therapy (IMT) had a mean HbA_1c of 6.7 ± 1.2%, compared with 7.1 ± 0.8% for those who underwent sleeve gastrectomy and IMT, and 8.4 ± 2.3% for IMT alone, reported Dr Sangeeta R. Kashyap of the Cleveland Clinic and colleagues.

While both surgical procedures resulted in similar reductions in body weight, body mass index, and total body fat percentage at 24 months, gastric bypass resulted in the greatest absolute truncal fat reductions (–16% vs. –10%; P = .04), according to the findings, which were published online (Diabetes Care 2013 Feb. 25 [doi:10.2337/dc12-1596]).

The 2-year study enrolled a subset of 60 patients from the 1-year STAMPEDE trial, which evaluated the efficacy and safety of IMT alone – pharmacotherapy in conjunction with lifestyle interventions – or IMT combined with gastric bypass or sleeve gastrectomy. Of the 54 patients who completed the trial, the average age was 48.4 years, with a mean BMI of 36 kg/m²; most patients were taking at least three different diabetes medications.

The study extension examined the effects of the three treatment approaches on glucose control, pancreatic beta-cell function including insulin secretion and sensitivity, and body composition.

"Other long-term observational studies have documented greater relapse rates for glycemic control after gastric restrictive procedures such as sleeve gastrectomy, suggesting that surgical weight loss from enforced caloric restriction itself is insufficient to halt the disease," reported Dr Kashyap and colleagues. "Our results extend the findings from our initial 12-month report and suggest factors beyond weight loss that are specific to intestinal bypass patients help regulate glucose levels and restore pancreatic beta-cell function."

Gastric bypass was the only treatment to have any significant effects on pancreatic beta-cell function, with a median 5.8-fold (quartile 1: –7.00; quartile Q3: 11.29) increase in beta-cell function from baseline compared with only negligible increases for sleeve gastrectomy and IMT.

Researchers also observed a 2.7-fold (N = 9, 3.8 vs. 1.4; P < .001) increase in insulin sensitivity with gastric bypass among subjects not using insulin, compared with a 1.2-fold (N=10; 5.8 vs. 5.3) increase after sleeve gastrectomy, and no change in those randomized to IMT (2.6 vs. 2.4; P = NS).

"Bariatric surgery, particularly gastric bypass surgery, uniquely restores normal glucose tolerance and pancreatic [beta]-cell function, presumably by targeting the truncal fat that represents the core metabolic defect involved in diabetes pathogenesis," the researchers wrote.

Primary funding for the study came from Ethicon Endo-Surgery, with ancillary funding from the American Diabetes Association and the National Institutes of Health. The authors reported receiving research grants, consultations and honoraria from various companies and organizations, and one author received grants and honoraria from Ethicon Endo-Surgery as scientific advisory board member, consultant, and speaker.

Gastric bypass leads to more significant and durable improvements in glycemic control than does sleeve gastrectomy or intensive medical therapy in moderately obese patients with type 2 diabetes, a prospective, randomized controlled trial has found.

Two years after the procedure, patients randomized to Roux-en-Y gastric bypass plus intensive medical therapy (IMT) had a mean HbA_1c of 6.7 ± 1.2%, compared with 7.1 ± 0.8% for those who underwent sleeve gastrectomy and IMT, and 8.4 ± 2.3% for IMT alone, reported Dr Sangeeta R. Kashyap of the Cleveland Clinic and colleagues.

While both surgical procedures resulted in similar reductions in body weight, body mass index, and total body fat percentage at 24 months, gastric bypass resulted in the greatest absolute truncal fat reductions (–16% vs. –10%; P = .04), according to the findings, which were published online (Diabetes Care 2013 Feb. 25 [doi:10.2337/dc12-1596]).

The 2-year study enrolled a subset of 60 patients from the 1-year STAMPEDE trial, which evaluated the efficacy and safety of IMT alone – pharmacotherapy in conjunction with lifestyle interventions – or IMT combined with gastric bypass or sleeve gastrectomy. Of the 54 patients who completed the trial, the average age was 48.4 years, with a mean BMI of 36 kg/m²; most patients were taking at least three different diabetes medications.

The study extension examined the effects of the three treatment approaches on glucose control, pancreatic beta-cell function including insulin secretion and sensitivity, and body composition.

"Other long-term observational studies have documented greater relapse rates for glycemic control after gastric restrictive procedures such as sleeve gastrectomy, suggesting that surgical weight loss from enforced caloric restriction itself is insufficient to halt the disease," reported Dr Kashyap and colleagues. "Our results extend the findings from our initial 12-month report and suggest factors beyond weight loss that are specific to intestinal bypass patients help regulate glucose levels and restore pancreatic beta-cell function."

Gastric bypass was the only treatment to have any significant effects on pancreatic beta-cell function, with a median 5.8-fold (quartile 1: –7.00; quartile Q3: 11.29) increase in beta-cell function from baseline compared with only negligible increases for sleeve gastrectomy and IMT.

Researchers also observed a 2.7-fold (N = 9, 3.8 vs. 1.4; P < .001) increase in insulin sensitivity with gastric bypass among subjects not using insulin, compared with a 1.2-fold (N=10; 5.8 vs. 5.3) increase after sleeve gastrectomy, and no change in those randomized to IMT (2.6 vs. 2.4; P = NS).

"Bariatric surgery, particularly gastric bypass surgery, uniquely restores normal glucose tolerance and pancreatic [beta]-cell function, presumably by targeting the truncal fat that represents the core metabolic defect involved in diabetes pathogenesis," the researchers wrote.

Primary funding for the study came from Ethicon Endo-Surgery, with ancillary funding from the American Diabetes Association and the National Institutes of Health. The authors reported receiving research grants, consultations and honoraria from various companies and organizations, and one author received grants and honoraria from Ethicon Endo-Surgery as scientific advisory board member, consultant, and speaker.

Gastric bypass leads to more significant and durable improvements in glycemic control than does sleeve gastrectomy or intensive medical therapy in moderately obese patients with type 2 diabetes, a prospective, randomized controlled trial has found.

Two years after the procedure, patients randomized to Roux-en-Y gastric bypass plus intensive medical therapy (IMT) had a mean HbA_1c of 6.7 ± 1.2%, compared with 7.1 ± 0.8% for those who underwent sleeve gastrectomy and IMT, and 8.4 ± 2.3% for IMT alone, reported Dr Sangeeta R. Kashyap of the Cleveland Clinic and colleagues.

While both surgical procedures resulted in similar reductions in body weight, body mass index, and total body fat percentage at 24 months, gastric bypass resulted in the greatest absolute truncal fat reductions (–16% vs. –10%; P = .04), according to the findings, which were published online (Diabetes Care 2013 Feb. 25 [doi:10.2337/dc12-1596]).

The 2-year study enrolled a subset of 60 patients from the 1-year STAMPEDE trial, which evaluated the efficacy and safety of IMT alone – pharmacotherapy in conjunction with lifestyle interventions – or IMT combined with gastric bypass or sleeve gastrectomy. Of the 54 patients who completed the trial, the average age was 48.4 years, with a mean BMI of 36 kg/m²; most patients were taking at least three different diabetes medications.

The study extension examined the effects of the three treatment approaches on glucose control, pancreatic beta-cell function including insulin secretion and sensitivity, and body composition.

"Other long-term observational studies have documented greater relapse rates for glycemic control after gastric restrictive procedures such as sleeve gastrectomy, suggesting that surgical weight loss from enforced caloric restriction itself is insufficient to halt the disease," reported Dr Kashyap and colleagues. "Our results extend the findings from our initial 12-month report and suggest factors beyond weight loss that are specific to intestinal bypass patients help regulate glucose levels and restore pancreatic beta-cell function."

Gastric bypass was the only treatment to have any significant effects on pancreatic beta-cell function, with a median 5.8-fold (quartile 1: –7.00; quartile Q3: 11.29) increase in beta-cell function from baseline compared with only negligible increases for sleeve gastrectomy and IMT.

Researchers also observed a 2.7-fold (N = 9, 3.8 vs. 1.4; P < .001) increase in insulin sensitivity with gastric bypass among subjects not using insulin, compared with a 1.2-fold (N=10; 5.8 vs. 5.3) increase after sleeve gastrectomy, and no change in those randomized to IMT (2.6 vs. 2.4; P = NS).

"Bariatric surgery, particularly gastric bypass surgery, uniquely restores normal glucose tolerance and pancreatic [beta]-cell function, presumably by targeting the truncal fat that represents the core metabolic defect involved in diabetes pathogenesis," the researchers wrote.

Primary funding for the study came from Ethicon Endo-Surgery, with ancillary funding from the American Diabetes Association and the National Institutes of Health. The authors reported receiving research grants, consultations and honoraria from various companies and organizations, and one author received grants and honoraria from Ethicon Endo-Surgery as scientific advisory board member, consultant, and speaker.