Kate Johnson

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.

MONTREAL — Community-acquired strains are the most common source of methicillin-resistant Staphylococcus aureus colonization and infection in babies in the neonatal intensive care unit, even though they have never left the hospital, researchers have found.

Findings in a 5-year retrospective study of 50 MRSA-colonized neonates in the NICU were presented at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“There are higher rates of community-acquired MRSA infection in our neonates than in our general adult and pediatric patient population,” lead investigator Dr. Gweneth Lazenby of the Medical University of South Carolina in Charleston said in an interview. “This is a call for people to help us really detail the sources of such early colonization, how we can prevent it, and how we can prevent subsequent infection.”

Theories on how neonates are exposed to MRSA in the NICU include maternal transmission, transmission from other family members or hospital workers, contaminated equipment, and a recently reported possible transmission through breast milk, she said.

“We have some concern about family members and maternal transmission to neonates, and so we would like to consider interrupting transmission by possibly culturing the individuals the babies are exposed to—including health care workers.”

In the current study, there was a mean of 21 days between birth and colonization of the 50 infants. However, 30% tested positive within 7 days of birth, she said.

“The 30% of infants who acquired early MRSA colonization, within the first week, were 2.5 times more likely to go on to develop infection,” she explained. No other risk factors for infection—including ethnicity, sex, method of delivery, gestational age, or length of stay—could be identified, although there was a nonsignificant trend toward a higher risk with lower birth weight.

In total, 16 of the 50 colonized infants (32%) eventually developed MRSA infections, which included eight blood stream infections, six skin and soft tissue infections, and two ventilator-associated pneumonia cases.

One of the bloodstream infections was fatal and was identified as a community-acquired MRSA strain (USA 300).

Pulse field gel electrophoresis identified USA 300 in 36% of 14 colonizing strains and 56% of 9 infection strains, she said. “This is considerably higher than what is seen in the rest of our hospital's pediatric and adult patient population, where we see a 4%-6% colonization rate and a 19% infection rate, with one-quarter of those infections being community acquired.”

Dr. Lazenby said decolonization is not currently attempted in neonates. “No one has looked at the effect of topical decolonization, and we do try to be as minimally invasive as possible with neonates in the NICU.”

The current management of colonized infants is isolation and contact precautions to prevent spreading the infection to other babies, she said.

Disclosures: None was reported.

MONTREAL — Community-acquired strains are the most common source of methicillin-resistant Staphylococcus aureus colonization and infection in babies in the neonatal intensive care unit, even though they have never left the hospital, researchers have found.

Findings in a 5-year retrospective study of 50 MRSA-colonized neonates in the NICU were presented at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“There are higher rates of community-acquired MRSA infection in our neonates than in our general adult and pediatric patient population,” lead investigator Dr. Gweneth Lazenby of the Medical University of South Carolina in Charleston said in an interview. “This is a call for people to help us really detail the sources of such early colonization, how we can prevent it, and how we can prevent subsequent infection.”

Theories on how neonates are exposed to MRSA in the NICU include maternal transmission, transmission from other family members or hospital workers, contaminated equipment, and a recently reported possible transmission through breast milk, she said.

“We have some concern about family members and maternal transmission to neonates, and so we would like to consider interrupting transmission by possibly culturing the individuals the babies are exposed to—including health care workers.”

In the current study, there was a mean of 21 days between birth and colonization of the 50 infants. However, 30% tested positive within 7 days of birth, she said.

“The 30% of infants who acquired early MRSA colonization, within the first week, were 2.5 times more likely to go on to develop infection,” she explained. No other risk factors for infection—including ethnicity, sex, method of delivery, gestational age, or length of stay—could be identified, although there was a nonsignificant trend toward a higher risk with lower birth weight.

In total, 16 of the 50 colonized infants (32%) eventually developed MRSA infections, which included eight blood stream infections, six skin and soft tissue infections, and two ventilator-associated pneumonia cases.

One of the bloodstream infections was fatal and was identified as a community-acquired MRSA strain (USA 300).

Pulse field gel electrophoresis identified USA 300 in 36% of 14 colonizing strains and 56% of 9 infection strains, she said. “This is considerably higher than what is seen in the rest of our hospital's pediatric and adult patient population, where we see a 4%-6% colonization rate and a 19% infection rate, with one-quarter of those infections being community acquired.”

Dr. Lazenby said decolonization is not currently attempted in neonates. “No one has looked at the effect of topical decolonization, and we do try to be as minimally invasive as possible with neonates in the NICU.”

The current management of colonized infants is isolation and contact precautions to prevent spreading the infection to other babies, she said.

Disclosures: None was reported.

MONTREAL — Community-acquired strains are the most common source of methicillin-resistant Staphylococcus aureus colonization and infection in babies in the neonatal intensive care unit, even though they have never left the hospital, researchers have found.

Findings in a 5-year retrospective study of 50 MRSA-colonized neonates in the NICU were presented at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“There are higher rates of community-acquired MRSA infection in our neonates than in our general adult and pediatric patient population,” lead investigator Dr. Gweneth Lazenby of the Medical University of South Carolina in Charleston said in an interview. “This is a call for people to help us really detail the sources of such early colonization, how we can prevent it, and how we can prevent subsequent infection.”

Theories on how neonates are exposed to MRSA in the NICU include maternal transmission, transmission from other family members or hospital workers, contaminated equipment, and a recently reported possible transmission through breast milk, she said.

“We have some concern about family members and maternal transmission to neonates, and so we would like to consider interrupting transmission by possibly culturing the individuals the babies are exposed to—including health care workers.”

In the current study, there was a mean of 21 days between birth and colonization of the 50 infants. However, 30% tested positive within 7 days of birth, she said.

“The 30% of infants who acquired early MRSA colonization, within the first week, were 2.5 times more likely to go on to develop infection,” she explained. No other risk factors for infection—including ethnicity, sex, method of delivery, gestational age, or length of stay—could be identified, although there was a nonsignificant trend toward a higher risk with lower birth weight.

In total, 16 of the 50 colonized infants (32%) eventually developed MRSA infections, which included eight blood stream infections, six skin and soft tissue infections, and two ventilator-associated pneumonia cases.

One of the bloodstream infections was fatal and was identified as a community-acquired MRSA strain (USA 300).

Pulse field gel electrophoresis identified USA 300 in 36% of 14 colonizing strains and 56% of 9 infection strains, she said. “This is considerably higher than what is seen in the rest of our hospital's pediatric and adult patient population, where we see a 4%-6% colonization rate and a 19% infection rate, with one-quarter of those infections being community acquired.”

Dr. Lazenby said decolonization is not currently attempted in neonates. “No one has looked at the effect of topical decolonization, and we do try to be as minimally invasive as possible with neonates in the NICU.”

The current management of colonized infants is isolation and contact precautions to prevent spreading the infection to other babies, she said.

Disclosures: None was reported.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence—which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996-1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” Dr. Zesiewicz said.

However, the new guidelines provide evidence-based recommendations for treating four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, and REM sleep behavior disorder; fatigue; and anxiety.

After conducting a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction (ED) in Parkinson's disease, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.”

Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, the authors recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests.”

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warned. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, who is a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim Inc. and Teva Pharmaceutical Industries Ltd.

She also reported that she had received research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence—which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996-1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” Dr. Zesiewicz said.

However, the new guidelines provide evidence-based recommendations for treating four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, and REM sleep behavior disorder; fatigue; and anxiety.

After conducting a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction (ED) in Parkinson's disease, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.”

Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, the authors recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests.”

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warned. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, who is a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim Inc. and Teva Pharmaceutical Industries Ltd.

She also reported that she had received research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence—which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996-1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” Dr. Zesiewicz said.

However, the new guidelines provide evidence-based recommendations for treating four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, and REM sleep behavior disorder; fatigue; and anxiety.

After conducting a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction (ED) in Parkinson's disease, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.”

Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, the authors recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests.”

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warned. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, who is a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim Inc. and Teva Pharmaceutical Industries Ltd.

She also reported that she had received research support from various pharmaceutical companies.

QUEBEC CITY — Levels of von Willebrand's factor antigen have the potential to provide a sensitive, noninvasive way to monitor disease activity in children with vasculitis involving the central nervous system, Dr. Tania Cellucci and colleagues reported at the annual meeting of the Canadian Rheumatology Association.

Knowing that CNS vasculitis is an autoimmune condition that affects the blood vessel walls, Dr. Cellucci and her colleagues at Toronto's Hospital for Sick Children reasoned that it might impact the release of von Willebrand's factor (vWF) antigen. So they set out to explore vWF levels in 31 consecutive pediatric CNS vasculitis patients from diagnosis through 24 months of follow-up.

The single-center cohort study ran between June 1989 and October 2008. The median age of the patients at diagnosis was 9 years, and 52% were female.

Demographic, clinical, laboratory, imaging, and histologic data were examined at diagnosis and at regular intervals throughout follow-up. Disease activity was measured at diagnosis and every 3 months thereafter using the physician global assessment visual analog scale, and levels of vWF were also measured at these intervals.

Only 10% of the cohort had secondary CNS vasculitis, whereas the remainder had childhood primary angiitis of the CNS (cPACNS), the researchers reported in their poster. More than half of the cohort (58%) had angiography-negative cPACNS, indicating small-vessel disease, whereas 32% had angiography-positive (large-vessel) cPACNS, which was divided evenly between the progressive and nonprogressive form.

As expected, abnormal levels of C-reactive protein (greater than 8 mg/L) and erythrocyte sedimentation rate (greater than 10 mm/h) were not consistent across the cohort at diagnosis, occurring in 20% and 55%, respectively. Leukocytosis (WBC greater than 10 × 109/L) was present in 52%. Opening pressure on lumbar puncture (greater than 20 cm H₂O) was increased in 62%, and elevated cerebrospinal fluid protein (greater than 0.4 g/L) and cerebrospinal fluid leukocytosis (greater than 5 × 106/L) were present in 54% and 72%, respectively. Abnormal magnetic resonance imaging was the most consistent finding, occurring in 94% of the cohort, with vasculitis on brain biopsy present in 71% and abnormal CNS angiogram present in 42%, they reported.

Disease activity decreased significantly and consistently from diagnosis and treatment initiation throughout the course of the study (P less than .0001), reported the researchers, although patients with angiography-negative cPACNS had consistently higher disease activity over time.

At diagnosis, the mean physician global assessment score for all patients with cPACNS was 5.7 for those with angiography-negative disease, and 6.5 for those with positive angiography. By 6 months, the mean scores for the angiography-positive patients had dropped to 1.2, whereas the mean angiography-negative score was 3.3. At 12 months, the mean score for the angiography-negative group was 1.6 vs. 0.9 for the angiography-positive group. Finally, at 24 months, the mean score for the negative group was 2.1, and 0.03 for the positive group.

Mirroring disease activity scores, levels of vWF also decreased over time in all patients (P = .0084) and mirrored disease activity scores, although they were significantly different between subtypes of cPACNS (P = .0028), reported Dr. Cellucci. The study demonstrates that vWF is a sensitive measure of disease activity, she said.

In the example of a stable patient who suddenly develops headaches or other symptoms, “a vWF level could help us figure out whether these new symptoms are due to active disease,” said Dr. Cellucci, who is a fellow in pediatric rheumatology at the University of Toronto. “If vWF is now elevated—and the patient had a high vWF at diagnosis—then this is consistent with a disease flare and we would not need to repeat the invasive tests. If it is normal, then this suggests the new symptoms are not due to disease flare,” she said. She did not define what an abnormal vWF might be, explaining that “all lab reports state the normal ranges for their lab and so the physician will be able to determine whether the level is abnormal or not.”

Dr. Cellucci added that an elevated vWF level can also assist in the diagnosis of pediatric CNS vasculitis, but is not specific enough in isolation. Symptomatic patients would still need invasive diagnostic tests, but an elevated vWF would be consistent with CNS vasculitis, thus guiding the clinician in ordering the work-up, she said.

Disclosures: Dr. Cellucci had no conflicts of interest to report.

Hyperintensity (arrow) in a teen with CNS angiitis is shown on FLAIR image.

Source © 2009 Elsevier Inc.

QUEBEC CITY — Levels of von Willebrand's factor antigen have the potential to provide a sensitive, noninvasive way to monitor disease activity in children with vasculitis involving the central nervous system, Dr. Tania Cellucci and colleagues reported at the annual meeting of the Canadian Rheumatology Association.

Knowing that CNS vasculitis is an autoimmune condition that affects the blood vessel walls, Dr. Cellucci and her colleagues at Toronto's Hospital for Sick Children reasoned that it might impact the release of von Willebrand's factor (vWF) antigen. So they set out to explore vWF levels in 31 consecutive pediatric CNS vasculitis patients from diagnosis through 24 months of follow-up.

The single-center cohort study ran between June 1989 and October 2008. The median age of the patients at diagnosis was 9 years, and 52% were female.

Demographic, clinical, laboratory, imaging, and histologic data were examined at diagnosis and at regular intervals throughout follow-up. Disease activity was measured at diagnosis and every 3 months thereafter using the physician global assessment visual analog scale, and levels of vWF were also measured at these intervals.

Only 10% of the cohort had secondary CNS vasculitis, whereas the remainder had childhood primary angiitis of the CNS (cPACNS), the researchers reported in their poster. More than half of the cohort (58%) had angiography-negative cPACNS, indicating small-vessel disease, whereas 32% had angiography-positive (large-vessel) cPACNS, which was divided evenly between the progressive and nonprogressive form.

As expected, abnormal levels of C-reactive protein (greater than 8 mg/L) and erythrocyte sedimentation rate (greater than 10 mm/h) were not consistent across the cohort at diagnosis, occurring in 20% and 55%, respectively. Leukocytosis (WBC greater than 10 × 109/L) was present in 52%. Opening pressure on lumbar puncture (greater than 20 cm H₂O) was increased in 62%, and elevated cerebrospinal fluid protein (greater than 0.4 g/L) and cerebrospinal fluid leukocytosis (greater than 5 × 106/L) were present in 54% and 72%, respectively. Abnormal magnetic resonance imaging was the most consistent finding, occurring in 94% of the cohort, with vasculitis on brain biopsy present in 71% and abnormal CNS angiogram present in 42%, they reported.

Disease activity decreased significantly and consistently from diagnosis and treatment initiation throughout the course of the study (P less than .0001), reported the researchers, although patients with angiography-negative cPACNS had consistently higher disease activity over time.

At diagnosis, the mean physician global assessment score for all patients with cPACNS was 5.7 for those with angiography-negative disease, and 6.5 for those with positive angiography. By 6 months, the mean scores for the angiography-positive patients had dropped to 1.2, whereas the mean angiography-negative score was 3.3. At 12 months, the mean score for the angiography-negative group was 1.6 vs. 0.9 for the angiography-positive group. Finally, at 24 months, the mean score for the negative group was 2.1, and 0.03 for the positive group.

Mirroring disease activity scores, levels of vWF also decreased over time in all patients (P = .0084) and mirrored disease activity scores, although they were significantly different between subtypes of cPACNS (P = .0028), reported Dr. Cellucci. The study demonstrates that vWF is a sensitive measure of disease activity, she said.

In the example of a stable patient who suddenly develops headaches or other symptoms, “a vWF level could help us figure out whether these new symptoms are due to active disease,” said Dr. Cellucci, who is a fellow in pediatric rheumatology at the University of Toronto. “If vWF is now elevated—and the patient had a high vWF at diagnosis—then this is consistent with a disease flare and we would not need to repeat the invasive tests. If it is normal, then this suggests the new symptoms are not due to disease flare,” she said. She did not define what an abnormal vWF might be, explaining that “all lab reports state the normal ranges for their lab and so the physician will be able to determine whether the level is abnormal or not.”

Dr. Cellucci added that an elevated vWF level can also assist in the diagnosis of pediatric CNS vasculitis, but is not specific enough in isolation. Symptomatic patients would still need invasive diagnostic tests, but an elevated vWF would be consistent with CNS vasculitis, thus guiding the clinician in ordering the work-up, she said.

Disclosures: Dr. Cellucci had no conflicts of interest to report.

Hyperintensity (arrow) in a teen with CNS angiitis is shown on FLAIR image.

Source © 2009 Elsevier Inc.

QUEBEC CITY — Levels of von Willebrand's factor antigen have the potential to provide a sensitive, noninvasive way to monitor disease activity in children with vasculitis involving the central nervous system, Dr. Tania Cellucci and colleagues reported at the annual meeting of the Canadian Rheumatology Association.

Knowing that CNS vasculitis is an autoimmune condition that affects the blood vessel walls, Dr. Cellucci and her colleagues at Toronto's Hospital for Sick Children reasoned that it might impact the release of von Willebrand's factor (vWF) antigen. So they set out to explore vWF levels in 31 consecutive pediatric CNS vasculitis patients from diagnosis through 24 months of follow-up.

The single-center cohort study ran between June 1989 and October 2008. The median age of the patients at diagnosis was 9 years, and 52% were female.

Demographic, clinical, laboratory, imaging, and histologic data were examined at diagnosis and at regular intervals throughout follow-up. Disease activity was measured at diagnosis and every 3 months thereafter using the physician global assessment visual analog scale, and levels of vWF were also measured at these intervals.

Only 10% of the cohort had secondary CNS vasculitis, whereas the remainder had childhood primary angiitis of the CNS (cPACNS), the researchers reported in their poster. More than half of the cohort (58%) had angiography-negative cPACNS, indicating small-vessel disease, whereas 32% had angiography-positive (large-vessel) cPACNS, which was divided evenly between the progressive and nonprogressive form.

As expected, abnormal levels of C-reactive protein (greater than 8 mg/L) and erythrocyte sedimentation rate (greater than 10 mm/h) were not consistent across the cohort at diagnosis, occurring in 20% and 55%, respectively. Leukocytosis (WBC greater than 10 × 109/L) was present in 52%. Opening pressure on lumbar puncture (greater than 20 cm H₂O) was increased in 62%, and elevated cerebrospinal fluid protein (greater than 0.4 g/L) and cerebrospinal fluid leukocytosis (greater than 5 × 106/L) were present in 54% and 72%, respectively. Abnormal magnetic resonance imaging was the most consistent finding, occurring in 94% of the cohort, with vasculitis on brain biopsy present in 71% and abnormal CNS angiogram present in 42%, they reported.

Disease activity decreased significantly and consistently from diagnosis and treatment initiation throughout the course of the study (P less than .0001), reported the researchers, although patients with angiography-negative cPACNS had consistently higher disease activity over time.

At diagnosis, the mean physician global assessment score for all patients with cPACNS was 5.7 for those with angiography-negative disease, and 6.5 for those with positive angiography. By 6 months, the mean scores for the angiography-positive patients had dropped to 1.2, whereas the mean angiography-negative score was 3.3. At 12 months, the mean score for the angiography-negative group was 1.6 vs. 0.9 for the angiography-positive group. Finally, at 24 months, the mean score for the negative group was 2.1, and 0.03 for the positive group.

Mirroring disease activity scores, levels of vWF also decreased over time in all patients (P = .0084) and mirrored disease activity scores, although they were significantly different between subtypes of cPACNS (P = .0028), reported Dr. Cellucci. The study demonstrates that vWF is a sensitive measure of disease activity, she said.

In the example of a stable patient who suddenly develops headaches or other symptoms, “a vWF level could help us figure out whether these new symptoms are due to active disease,” said Dr. Cellucci, who is a fellow in pediatric rheumatology at the University of Toronto. “If vWF is now elevated—and the patient had a high vWF at diagnosis—then this is consistent with a disease flare and we would not need to repeat the invasive tests. If it is normal, then this suggests the new symptoms are not due to disease flare,” she said. She did not define what an abnormal vWF might be, explaining that “all lab reports state the normal ranges for their lab and so the physician will be able to determine whether the level is abnormal or not.”

Dr. Cellucci added that an elevated vWF level can also assist in the diagnosis of pediatric CNS vasculitis, but is not specific enough in isolation. Symptomatic patients would still need invasive diagnostic tests, but an elevated vWF would be consistent with CNS vasculitis, thus guiding the clinician in ordering the work-up, she said.

Disclosures: Dr. Cellucci had no conflicts of interest to report.

Hyperintensity (arrow) in a teen with CNS angiitis is shown on FLAIR image.

Source © 2009 Elsevier Inc.

MONTREAL — Occurance of injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” Dr. Dafna Gladman, the study's principal investigator, told Rheumatology News.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA. Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls).

The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA. “We actually examined all the patients with psoriasis to make sure they didn't have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.” She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Disclosures: Dr. Gladman declared no conflicts of interest.

Changes in the interphalangeal joints are shown in this x-ray of a patient with PsA in both hands.

Source © 2010 National Medical Slide Bank/Custom Medical Stock Photo, All Rights Reserved

My Take

Now We Need Prospective Trials

The potential impact of trauma on the development of psoriatic arthritis was first proposed over 50 years ago, when the observation of acryo-osteolysis in an injured digit was labeled “deep Koebner's effect.”

Two recent, retrospective, case-control studies analyzed the relationship between trauma and the onset of psoriatic arthritis. Corticosteroid use (in the first report) and immunization, moving house, and injury severe enough to require medical consultation (in the second report) were associated with incident PsA.

Dr. Gladman's study provides additional support for the association between trauma and incident PsA.

In this study, individuals with PsA were matched to psoriasis patients, and investigators found that injury requiring medical attention, heavy lifting, and severe infection were associated with the development of PsA.

Of course, many important questions remain to be addressed.

Could the retrospective designs of these case-control studies be strongly influenced by recall bias? This is possible but unlikely to account for these findings, given that both RA and psoriasis subjects have been used as controls.

A second question centers on the mechanisms that underlie this interesting association.

Two potential explanations have been suggested: the activation of proinflammatory molecules (such as nerve growth factor) that are produced in the psoriatic plaques, or high-level biomechanical stress to the synovial-entheseal complex, which triggers an innate immune response and subsequent inflammation.

Evidence amassed from several different sources supports the concept that trauma may be associated with the onset of PsA.

An adequately powered prospective study of psoriasis patients, with strict case definitions and appropriate control groups, will be required to adequately test the hypothesis and to understand the magnitude of a particular risk factor. Genetic risk factors could also be analyzed in such a study.

In the meantime, we await the details of Dr. Gladman's analysis, and we should make an effort to catalogue the events that are temporally related to the onset of inflammatory arthritis in our patients.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine at the University of Rochester (N.Y.). He reports having no relevant conflicts of interest.

MONTREAL — Occurance of injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” Dr. Dafna Gladman, the study's principal investigator, told Rheumatology News.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA. Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls).

The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA. “We actually examined all the patients with psoriasis to make sure they didn't have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.” She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Disclosures: Dr. Gladman declared no conflicts of interest.

Changes in the interphalangeal joints are shown in this x-ray of a patient with PsA in both hands.

Source © 2010 National Medical Slide Bank/Custom Medical Stock Photo, All Rights Reserved

My Take

Now We Need Prospective Trials

The potential impact of trauma on the development of psoriatic arthritis was first proposed over 50 years ago, when the observation of acryo-osteolysis in an injured digit was labeled “deep Koebner's effect.”

Two recent, retrospective, case-control studies analyzed the relationship between trauma and the onset of psoriatic arthritis. Corticosteroid use (in the first report) and immunization, moving house, and injury severe enough to require medical consultation (in the second report) were associated with incident PsA.

Dr. Gladman's study provides additional support for the association between trauma and incident PsA.

In this study, individuals with PsA were matched to psoriasis patients, and investigators found that injury requiring medical attention, heavy lifting, and severe infection were associated with the development of PsA.

Of course, many important questions remain to be addressed.

Could the retrospective designs of these case-control studies be strongly influenced by recall bias? This is possible but unlikely to account for these findings, given that both RA and psoriasis subjects have been used as controls.

A second question centers on the mechanisms that underlie this interesting association.

Two potential explanations have been suggested: the activation of proinflammatory molecules (such as nerve growth factor) that are produced in the psoriatic plaques, or high-level biomechanical stress to the synovial-entheseal complex, which triggers an innate immune response and subsequent inflammation.

Evidence amassed from several different sources supports the concept that trauma may be associated with the onset of PsA.

An adequately powered prospective study of psoriasis patients, with strict case definitions and appropriate control groups, will be required to adequately test the hypothesis and to understand the magnitude of a particular risk factor. Genetic risk factors could also be analyzed in such a study.

In the meantime, we await the details of Dr. Gladman's analysis, and we should make an effort to catalogue the events that are temporally related to the onset of inflammatory arthritis in our patients.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine at the University of Rochester (N.Y.). He reports having no relevant conflicts of interest.

MONTREAL — Occurance of injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” Dr. Dafna Gladman, the study's principal investigator, told Rheumatology News.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA. Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls).

The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA. “We actually examined all the patients with psoriasis to make sure they didn't have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.” She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Disclosures: Dr. Gladman declared no conflicts of interest.

Changes in the interphalangeal joints are shown in this x-ray of a patient with PsA in both hands.

Source © 2010 National Medical Slide Bank/Custom Medical Stock Photo, All Rights Reserved

My Take

Now We Need Prospective Trials

The potential impact of trauma on the development of psoriatic arthritis was first proposed over 50 years ago, when the observation of acryo-osteolysis in an injured digit was labeled “deep Koebner's effect.”

Two recent, retrospective, case-control studies analyzed the relationship between trauma and the onset of psoriatic arthritis. Corticosteroid use (in the first report) and immunization, moving house, and injury severe enough to require medical consultation (in the second report) were associated with incident PsA.

Dr. Gladman's study provides additional support for the association between trauma and incident PsA.

In this study, individuals with PsA were matched to psoriasis patients, and investigators found that injury requiring medical attention, heavy lifting, and severe infection were associated with the development of PsA.

Of course, many important questions remain to be addressed.

Could the retrospective designs of these case-control studies be strongly influenced by recall bias? This is possible but unlikely to account for these findings, given that both RA and psoriasis subjects have been used as controls.

A second question centers on the mechanisms that underlie this interesting association.

Two potential explanations have been suggested: the activation of proinflammatory molecules (such as nerve growth factor) that are produced in the psoriatic plaques, or high-level biomechanical stress to the synovial-entheseal complex, which triggers an innate immune response and subsequent inflammation.

Evidence amassed from several different sources supports the concept that trauma may be associated with the onset of PsA.

An adequately powered prospective study of psoriasis patients, with strict case definitions and appropriate control groups, will be required to adequately test the hypothesis and to understand the magnitude of a particular risk factor. Genetic risk factors could also be analyzed in such a study.

In the meantime, we await the details of Dr. Gladman's analysis, and we should make an effort to catalogue the events that are temporally related to the onset of inflammatory arthritis in our patients.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine at the University of Rochester (N.Y.). He reports having no relevant conflicts of interest.

While infant hearing loss is more frequently screened for and identified in the United States than it was a decade ago, the challenge has now shifted toward the delivery of timely intervention when it's needed, according to a report from the Centers for Disease Control and Prevention.

“Now that [more than] 95% of U.S. infants can be documented as having their hearing screened, remaining challenges include ensuring timely diagnostic evaluation for those who did not pass the screening and enrollment in early intervention for those with diagnosed hearing loss,” wrote M. Gaffney and colleagues from the National Center on Birth Defects and Developmental Disabilities at the CDC.

Early Hearing Detection and Intervention (EHDI) programs established in all states and U.S. territories recommend that infants undergo hearing screening no later than age 1 month, diagnostic and audiologic evaluation no later than age 3 months for infants who do not pass the screening, and enrollment in early intervention no later than age 6 months for infants with diagnosed hearing loss.

But an analysis of CDC and EHDI surveillance data from 1999 through 2007, while showing an increase in screening from 47% to 97%, also found that 46% of infants who did not pass the final or most recent screening in 2007 were either lost to follow-up or lost to documentation (LFU/LTD). When the numbers are evaluated slightly differently, only 61% of infants diagnosed with hearing loss in 2007 were enrolled in early intervention by the age of 6 months (MMWR 2010:59;220-3).

“EHDI programs such as those in Massachusetts and Colorado, which often actively follow up with families and providers and reported LFU/LTD in 2007 of 5.6% and 6.4%, respectively, are good examples for other programs trying to improve overall follow-up rates,” the authors wrote.

The national 2007 LFU/LTD rate of 46% is an improvement over the 2005 rate of 64%, especially considering that more infants were screened and diagnosed with hearing loss in 2007. Indeed, while 52% of infants were screened and 56% of those diagnosed with hearing loss in 2000, 97% were screened and 42% were diagnosed in 2007.

The CDC report outlines its three most significant limitations: The methods and definitions used in data collection differed over the course of the decade, limiting comparability; some states and territories could provide only limited data; and EHDI programs are not designed to detect mild hearing loss below the threshold of 30-40 dB or progressive or late-onset hearing loss.

While infant hearing loss is more frequently screened for and identified in the United States than it was a decade ago, the challenge has now shifted toward the delivery of timely intervention when it's needed, according to a report from the Centers for Disease Control and Prevention.

“Now that [more than] 95% of U.S. infants can be documented as having their hearing screened, remaining challenges include ensuring timely diagnostic evaluation for those who did not pass the screening and enrollment in early intervention for those with diagnosed hearing loss,” wrote M. Gaffney and colleagues from the National Center on Birth Defects and Developmental Disabilities at the CDC.

Early Hearing Detection and Intervention (EHDI) programs established in all states and U.S. territories recommend that infants undergo hearing screening no later than age 1 month, diagnostic and audiologic evaluation no later than age 3 months for infants who do not pass the screening, and enrollment in early intervention no later than age 6 months for infants with diagnosed hearing loss.

But an analysis of CDC and EHDI surveillance data from 1999 through 2007, while showing an increase in screening from 47% to 97%, also found that 46% of infants who did not pass the final or most recent screening in 2007 were either lost to follow-up or lost to documentation (LFU/LTD). When the numbers are evaluated slightly differently, only 61% of infants diagnosed with hearing loss in 2007 were enrolled in early intervention by the age of 6 months (MMWR 2010:59;220-3).

“EHDI programs such as those in Massachusetts and Colorado, which often actively follow up with families and providers and reported LFU/LTD in 2007 of 5.6% and 6.4%, respectively, are good examples for other programs trying to improve overall follow-up rates,” the authors wrote.

The national 2007 LFU/LTD rate of 46% is an improvement over the 2005 rate of 64%, especially considering that more infants were screened and diagnosed with hearing loss in 2007. Indeed, while 52% of infants were screened and 56% of those diagnosed with hearing loss in 2000, 97% were screened and 42% were diagnosed in 2007.

The CDC report outlines its three most significant limitations: The methods and definitions used in data collection differed over the course of the decade, limiting comparability; some states and territories could provide only limited data; and EHDI programs are not designed to detect mild hearing loss below the threshold of 30-40 dB or progressive or late-onset hearing loss.

While infant hearing loss is more frequently screened for and identified in the United States than it was a decade ago, the challenge has now shifted toward the delivery of timely intervention when it's needed, according to a report from the Centers for Disease Control and Prevention.

“Now that [more than] 95% of U.S. infants can be documented as having their hearing screened, remaining challenges include ensuring timely diagnostic evaluation for those who did not pass the screening and enrollment in early intervention for those with diagnosed hearing loss,” wrote M. Gaffney and colleagues from the National Center on Birth Defects and Developmental Disabilities at the CDC.

Early Hearing Detection and Intervention (EHDI) programs established in all states and U.S. territories recommend that infants undergo hearing screening no later than age 1 month, diagnostic and audiologic evaluation no later than age 3 months for infants who do not pass the screening, and enrollment in early intervention no later than age 6 months for infants with diagnosed hearing loss.

But an analysis of CDC and EHDI surveillance data from 1999 through 2007, while showing an increase in screening from 47% to 97%, also found that 46% of infants who did not pass the final or most recent screening in 2007 were either lost to follow-up or lost to documentation (LFU/LTD). When the numbers are evaluated slightly differently, only 61% of infants diagnosed with hearing loss in 2007 were enrolled in early intervention by the age of 6 months (MMWR 2010:59;220-3).

“EHDI programs such as those in Massachusetts and Colorado, which often actively follow up with families and providers and reported LFU/LTD in 2007 of 5.6% and 6.4%, respectively, are good examples for other programs trying to improve overall follow-up rates,” the authors wrote.

The national 2007 LFU/LTD rate of 46% is an improvement over the 2005 rate of 64%, especially considering that more infants were screened and diagnosed with hearing loss in 2007. Indeed, while 52% of infants were screened and 56% of those diagnosed with hearing loss in 2000, 97% were screened and 42% were diagnosed in 2007.

The CDC report outlines its three most significant limitations: The methods and definitions used in data collection differed over the course of the decade, limiting comparability; some states and territories could provide only limited data; and EHDI programs are not designed to detect mild hearing loss below the threshold of 30-40 dB or progressive or late-onset hearing loss.

MONTREAL – Primary care physicians are not confident when it comes to diagnosing and managing patients with bipolar depression, according to a cross-sectional survey of providers participating in a national electronic health record database.

Among 85 primary care providers in GE Healthcare's Medical Quality Improvement Consortium, self-rated confidence in managing bipolar disorder averaged 1.7 on a scale of 1–5, with 5 being “very confident,” said Dr. Dana King, who presented the findings as a poster at the annual meeting of the North American Primary Care Research Group.

“For other more common disorders such as reflux disease, heart disease, or diabetes, these physicians have more confidence in their ability to sort out complex problems and deal with them. But bipolar disorder is less common and people have less exposure to it during their training,” explained Dr. King, professor of family medicine at the Medical University of South Carolina, Charleston.

Eighty-six percent of the respondents had been using electronic health records (EHRs) for 3 or more years, and 94% had access to the Internet from their clinical workstations.

Although 72% of the respondents said they screened depressed patients for bipolar disorder, only 38% reported frequently using a standard screening tool, the most common being the Mood Disorder Questionnaire.

Informal screening was more common than was the use of standardized tools and consisted of “a few questions about manic activity in patients with depression,” Dr. King said. Such information screening may involve questions such as “Do you go on spending sprees? Do you stay up all night? or Do you find yourself having ups and downs, including periods of high irritability, anger or stress?”

As the use of EHRs becomes more widespread, they may help prompt physicians to screen patients for bipolar disorder by offering pop-up information, he said. This represents an opportunity for quality improvement.

“Physicians seem to like the idea that we could offer them quick medical information via the [EHR] that will give them some quick answers,” he said.

“Many of them are willing to comanage the patient but they first want the diagnosis to be confirmed, typed according to bipolar I or II, with an identification of the phase and recommended medications. That was the preference of most of them,” he concluded.

The study was part of a quality improvement project funded by Delaware Valley Outcomes Research and GE Healthcare.

MONTREAL – Primary care physicians are not confident when it comes to diagnosing and managing patients with bipolar depression, according to a cross-sectional survey of providers participating in a national electronic health record database.

Among 85 primary care providers in GE Healthcare's Medical Quality Improvement Consortium, self-rated confidence in managing bipolar disorder averaged 1.7 on a scale of 1–5, with 5 being “very confident,” said Dr. Dana King, who presented the findings as a poster at the annual meeting of the North American Primary Care Research Group.

“For other more common disorders such as reflux disease, heart disease, or diabetes, these physicians have more confidence in their ability to sort out complex problems and deal with them. But bipolar disorder is less common and people have less exposure to it during their training,” explained Dr. King, professor of family medicine at the Medical University of South Carolina, Charleston.

Eighty-six percent of the respondents had been using electronic health records (EHRs) for 3 or more years, and 94% had access to the Internet from their clinical workstations.

Although 72% of the respondents said they screened depressed patients for bipolar disorder, only 38% reported frequently using a standard screening tool, the most common being the Mood Disorder Questionnaire.

Informal screening was more common than was the use of standardized tools and consisted of “a few questions about manic activity in patients with depression,” Dr. King said. Such information screening may involve questions such as “Do you go on spending sprees? Do you stay up all night? or Do you find yourself having ups and downs, including periods of high irritability, anger or stress?”

As the use of EHRs becomes more widespread, they may help prompt physicians to screen patients for bipolar disorder by offering pop-up information, he said. This represents an opportunity for quality improvement.

“Physicians seem to like the idea that we could offer them quick medical information via the [EHR] that will give them some quick answers,” he said.

“Many of them are willing to comanage the patient but they first want the diagnosis to be confirmed, typed according to bipolar I or II, with an identification of the phase and recommended medications. That was the preference of most of them,” he concluded.

The study was part of a quality improvement project funded by Delaware Valley Outcomes Research and GE Healthcare.

MONTREAL – Primary care physicians are not confident when it comes to diagnosing and managing patients with bipolar depression, according to a cross-sectional survey of providers participating in a national electronic health record database.

Among 85 primary care providers in GE Healthcare's Medical Quality Improvement Consortium, self-rated confidence in managing bipolar disorder averaged 1.7 on a scale of 1–5, with 5 being “very confident,” said Dr. Dana King, who presented the findings as a poster at the annual meeting of the North American Primary Care Research Group.

“For other more common disorders such as reflux disease, heart disease, or diabetes, these physicians have more confidence in their ability to sort out complex problems and deal with them. But bipolar disorder is less common and people have less exposure to it during their training,” explained Dr. King, professor of family medicine at the Medical University of South Carolina, Charleston.

Eighty-six percent of the respondents had been using electronic health records (EHRs) for 3 or more years, and 94% had access to the Internet from their clinical workstations.

Although 72% of the respondents said they screened depressed patients for bipolar disorder, only 38% reported frequently using a standard screening tool, the most common being the Mood Disorder Questionnaire.

Informal screening was more common than was the use of standardized tools and consisted of “a few questions about manic activity in patients with depression,” Dr. King said. Such information screening may involve questions such as “Do you go on spending sprees? Do you stay up all night? or Do you find yourself having ups and downs, including periods of high irritability, anger or stress?”

As the use of EHRs becomes more widespread, they may help prompt physicians to screen patients for bipolar disorder by offering pop-up information, he said. This represents an opportunity for quality improvement.

“Physicians seem to like the idea that we could offer them quick medical information via the [EHR] that will give them some quick answers,” he said.

“Many of them are willing to comanage the patient but they first want the diagnosis to be confirmed, typed according to bipolar I or II, with an identification of the phase and recommended medications. That was the preference of most of them,” he concluded.

The study was part of a quality improvement project funded by Delaware Valley Outcomes Research and GE Healthcare.