Patrice Wendling

Regular use of the inhaled anticholinergic tiotropium did not significantly reduce the rate of decline in mean forced expiratory volume in 1 second in patients with chronic obstructive pulmonary disease, a large randomized, double-blind trial has shown.

However, tiotropium was associated with improvements in the secondary end points of lung function, quality of life, and rate of exacerbations, according to the findings.

The trial, known as UPLIFT (Understanding Potential Long-Term Impacts on Function With Tiotropium), randomized 5,993 patients at 490 centers in 37 countries to 4 years of therapy with either tiotropium 18 mcg inhaled once daily or placebo. They were allowed to use other respiratory medications, except inhaled anticholinergics. Patients (mean age 66 years) had moderate to very severe COPD and a mean baseline forced expiratory volume in 1 second (FEV1) of 1.32 L after bronchodilation (48% of predicted value).

There were no significant differences between the treatment and placebo groups in the rate of decline in the mean values for FEV1 and forced vital capacity (FVC) either before or after bronchodilation from day 30 to the end of study, lead study author Dr. Donald P. Tashkin of the University of California, Los Angeles, and his associates reported. The annual rate of decline was 30 mL/yr in both groups before bronchodilation, and 40 mL in the tiotropium group and 42 mL in the placebo group after bronchodilation.

Mean absolute improvements in FEV1 in the tiotropium group, compared with the placebo group, were maintained at all time points after randomization, and ranged from 87 mL to 103 mL before bronchodilation and from 47 mL to 65 mL after bronchodilation. The differences were statistically significant.

The incidence of most serious adverse events was lower in the tiotropium group than in the placebo group, including a reduced risk of heart failure, COPD exacerbation, dyspnea, and respiratory failure, the authors wrote (N. Engl. J. Med. 2008;359:1543-54). In addition, the incidence rate for myocardial infarction was 0.69/100 patient-years for tiotropium, compared with 0.97/100 patient-years for placebo (relative risk, 0.71).

The incidence rate of cardiac failure, however, was 0.61/100 patient-years for tiotropium, compared with 0.48/100 patient-years for placebo (RR, 1.25).

Those findings are noteworthy, as a recently published meta-analysis showed that the use of either inhaled tiotropium or ipratropium significantly increased the risk of cardiovascular death, MI, or stroke by about 58% among patients with COPD (JAMA 2008;300:1439-50).

Pfizer Inc. and Boehringer Ingelheim GmbH, which comarket inhaled tiotropium under the trade name Spiriva and supported the UPLIFT trial, strongly rejected the findings of that meta-analysis.

The yearly rate of decline in FEV1 observed in UPLIFT was lower than rates reported in other trials, Dr. Tashkin and associates noted, including EUROSCOP (European Respiratory Society Study on Chronic Obstructive Pulmonary Disease) and ISOLDE (Inhaled Steroids in Obstructive Lung Disease in Europe).

A potential explanation for the discrepancies is that UPLIFT allowed for prescription of all respiratory therapies at the discretion of the physicians. In addition, only 30% of patients were current smokers at baseline, compared with 38%–90% in other studies. The UPLIFT investigators also cited differences in study design, patient selection, and regional factors.

The UPLIFT trial's failure to find a difference in the rates of decline in FEV1 might have been predictable, given previous trials' results and the fact that smoking cessation is the only intervention that meets the criteria of disease-modifying therapy, suggested Dr. John J. Reilly of the University of Pittsburgh in an accompanying editorial (N. Engl. J. Med. 2008;359:1616-8).

However, Dr. Reilly argued that the issue with UPLIFT and other recent large trials may be a signal-to-noise problem.

“There is increasing recognition that FEV1 alone, while important, does not capture and communicate the heterogeneity of COPD,” he wrote.

Dr. Reilly disclosed no relevant conflicts of interest. Dr. Tashkin reported receiving consulting and lecture fees from Boehringer Ingelheim and grant support from Boehringer Ingelheim and Pfizer.

Regular use of the inhaled anticholinergic tiotropium did not significantly reduce the rate of decline in mean forced expiratory volume in 1 second in patients with chronic obstructive pulmonary disease, a large randomized, double-blind trial has shown.

However, tiotropium was associated with improvements in the secondary end points of lung function, quality of life, and rate of exacerbations, according to the findings.

The trial, known as UPLIFT (Understanding Potential Long-Term Impacts on Function With Tiotropium), randomized 5,993 patients at 490 centers in 37 countries to 4 years of therapy with either tiotropium 18 mcg inhaled once daily or placebo. They were allowed to use other respiratory medications, except inhaled anticholinergics. Patients (mean age 66 years) had moderate to very severe COPD and a mean baseline forced expiratory volume in 1 second (FEV1) of 1.32 L after bronchodilation (48% of predicted value).

There were no significant differences between the treatment and placebo groups in the rate of decline in the mean values for FEV1 and forced vital capacity (FVC) either before or after bronchodilation from day 30 to the end of study, lead study author Dr. Donald P. Tashkin of the University of California, Los Angeles, and his associates reported. The annual rate of decline was 30 mL/yr in both groups before bronchodilation, and 40 mL in the tiotropium group and 42 mL in the placebo group after bronchodilation.

Mean absolute improvements in FEV1 in the tiotropium group, compared with the placebo group, were maintained at all time points after randomization, and ranged from 87 mL to 103 mL before bronchodilation and from 47 mL to 65 mL after bronchodilation. The differences were statistically significant.

The incidence of most serious adverse events was lower in the tiotropium group than in the placebo group, including a reduced risk of heart failure, COPD exacerbation, dyspnea, and respiratory failure, the authors wrote (N. Engl. J. Med. 2008;359:1543-54). In addition, the incidence rate for myocardial infarction was 0.69/100 patient-years for tiotropium, compared with 0.97/100 patient-years for placebo (relative risk, 0.71).

The incidence rate of cardiac failure, however, was 0.61/100 patient-years for tiotropium, compared with 0.48/100 patient-years for placebo (RR, 1.25).

Those findings are noteworthy, as a recently published meta-analysis showed that the use of either inhaled tiotropium or ipratropium significantly increased the risk of cardiovascular death, MI, or stroke by about 58% among patients with COPD (JAMA 2008;300:1439-50).

Pfizer Inc. and Boehringer Ingelheim GmbH, which comarket inhaled tiotropium under the trade name Spiriva and supported the UPLIFT trial, strongly rejected the findings of that meta-analysis.

The yearly rate of decline in FEV1 observed in UPLIFT was lower than rates reported in other trials, Dr. Tashkin and associates noted, including EUROSCOP (European Respiratory Society Study on Chronic Obstructive Pulmonary Disease) and ISOLDE (Inhaled Steroids in Obstructive Lung Disease in Europe).

A potential explanation for the discrepancies is that UPLIFT allowed for prescription of all respiratory therapies at the discretion of the physicians. In addition, only 30% of patients were current smokers at baseline, compared with 38%–90% in other studies. The UPLIFT investigators also cited differences in study design, patient selection, and regional factors.

The UPLIFT trial's failure to find a difference in the rates of decline in FEV1 might have been predictable, given previous trials' results and the fact that smoking cessation is the only intervention that meets the criteria of disease-modifying therapy, suggested Dr. John J. Reilly of the University of Pittsburgh in an accompanying editorial (N. Engl. J. Med. 2008;359:1616-8).

However, Dr. Reilly argued that the issue with UPLIFT and other recent large trials may be a signal-to-noise problem.

“There is increasing recognition that FEV1 alone, while important, does not capture and communicate the heterogeneity of COPD,” he wrote.

Dr. Reilly disclosed no relevant conflicts of interest. Dr. Tashkin reported receiving consulting and lecture fees from Boehringer Ingelheim and grant support from Boehringer Ingelheim and Pfizer.

Regular use of the inhaled anticholinergic tiotropium did not significantly reduce the rate of decline in mean forced expiratory volume in 1 second in patients with chronic obstructive pulmonary disease, a large randomized, double-blind trial has shown.

However, tiotropium was associated with improvements in the secondary end points of lung function, quality of life, and rate of exacerbations, according to the findings.

The trial, known as UPLIFT (Understanding Potential Long-Term Impacts on Function With Tiotropium), randomized 5,993 patients at 490 centers in 37 countries to 4 years of therapy with either tiotropium 18 mcg inhaled once daily or placebo. They were allowed to use other respiratory medications, except inhaled anticholinergics. Patients (mean age 66 years) had moderate to very severe COPD and a mean baseline forced expiratory volume in 1 second (FEV1) of 1.32 L after bronchodilation (48% of predicted value).

There were no significant differences between the treatment and placebo groups in the rate of decline in the mean values for FEV1 and forced vital capacity (FVC) either before or after bronchodilation from day 30 to the end of study, lead study author Dr. Donald P. Tashkin of the University of California, Los Angeles, and his associates reported. The annual rate of decline was 30 mL/yr in both groups before bronchodilation, and 40 mL in the tiotropium group and 42 mL in the placebo group after bronchodilation.

Mean absolute improvements in FEV1 in the tiotropium group, compared with the placebo group, were maintained at all time points after randomization, and ranged from 87 mL to 103 mL before bronchodilation and from 47 mL to 65 mL after bronchodilation. The differences were statistically significant.

The incidence of most serious adverse events was lower in the tiotropium group than in the placebo group, including a reduced risk of heart failure, COPD exacerbation, dyspnea, and respiratory failure, the authors wrote (N. Engl. J. Med. 2008;359:1543-54). In addition, the incidence rate for myocardial infarction was 0.69/100 patient-years for tiotropium, compared with 0.97/100 patient-years for placebo (relative risk, 0.71).

The incidence rate of cardiac failure, however, was 0.61/100 patient-years for tiotropium, compared with 0.48/100 patient-years for placebo (RR, 1.25).

Those findings are noteworthy, as a recently published meta-analysis showed that the use of either inhaled tiotropium or ipratropium significantly increased the risk of cardiovascular death, MI, or stroke by about 58% among patients with COPD (JAMA 2008;300:1439-50).

Pfizer Inc. and Boehringer Ingelheim GmbH, which comarket inhaled tiotropium under the trade name Spiriva and supported the UPLIFT trial, strongly rejected the findings of that meta-analysis.

The yearly rate of decline in FEV1 observed in UPLIFT was lower than rates reported in other trials, Dr. Tashkin and associates noted, including EUROSCOP (European Respiratory Society Study on Chronic Obstructive Pulmonary Disease) and ISOLDE (Inhaled Steroids in Obstructive Lung Disease in Europe).

A potential explanation for the discrepancies is that UPLIFT allowed for prescription of all respiratory therapies at the discretion of the physicians. In addition, only 30% of patients were current smokers at baseline, compared with 38%–90% in other studies. The UPLIFT investigators also cited differences in study design, patient selection, and regional factors.

The UPLIFT trial's failure to find a difference in the rates of decline in FEV1 might have been predictable, given previous trials' results and the fact that smoking cessation is the only intervention that meets the criteria of disease-modifying therapy, suggested Dr. John J. Reilly of the University of Pittsburgh in an accompanying editorial (N. Engl. J. Med. 2008;359:1616-8).

However, Dr. Reilly argued that the issue with UPLIFT and other recent large trials may be a signal-to-noise problem.

“There is increasing recognition that FEV1 alone, while important, does not capture and communicate the heterogeneity of COPD,” he wrote.

Dr. Reilly disclosed no relevant conflicts of interest. Dr. Tashkin reported receiving consulting and lecture fees from Boehringer Ingelheim and grant support from Boehringer Ingelheim and Pfizer.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

'It could be that if we were using PCR rather than cultures, we'd be seeing a lot more' K. kingae. DR. KAPLAN

An x-ray shows a lytic lesion (arrow) of the distal epiphysis of the femur. Courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

'It could be that if we were using PCR rather than cultures, we'd be seeing a lot more' K. kingae. DR. KAPLAN

An x-ray shows a lytic lesion (arrow) of the distal epiphysis of the femur. Courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

'It could be that if we were using PCR rather than cultures, we'd be seeing a lot more' K. kingae. DR. KAPLAN

An x-ray shows a lytic lesion (arrow) of the distal epiphysis of the femur. Courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

“PCR for Kingella is not set up at our place or many others now,” Dr. Kaplan said in an interview. “PCR for Kingella is mainly research at the moment, but is something that will be set up in the future.”

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

It also might not be a bad idea to hold on to culture plates a little longer, Dr. Kaplan advised.

At left, an x-ray of an 18-month-old patient showed a lytic lesion (arrow) of the distal epiphysis of the femur. At top right, a micrograph of an extracted isolate shows a gram-negative bacillus (arrow). At bottom right, a micrograph shows a growth of Kingella kingae, which may take up to 7 days to culture. Images courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

“PCR for Kingella is not set up at our place or many others now,” Dr. Kaplan said in an interview. “PCR for Kingella is mainly research at the moment, but is something that will be set up in the future.”

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

It also might not be a bad idea to hold on to culture plates a little longer, Dr. Kaplan advised.

At left, an x-ray of an 18-month-old patient showed a lytic lesion (arrow) of the distal epiphysis of the femur. At top right, a micrograph of an extracted isolate shows a gram-negative bacillus (arrow). At bottom right, a micrograph shows a growth of Kingella kingae, which may take up to 7 days to culture. Images courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Consider Kingella kingae as a cause of infection when diagnosing and treating children with suspected acute osteomyelitis, an infectious disease specialist advised.

The incidence of acute osteoarticular infections in young children has risen dramatically in recent years, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for the lion's share of osteomyelitis cases in the United States, said Dr. Sheldon L. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

But in some parts of the world, K. kingae is the most common cause of acute osteomyelitis and septic arthritis in infants and young children, Dr. Kaplan said at a meeting sponsored by the American Academy of Pediatrics. This global mismatch could be because a lot of children with suspected osteomyelitis are culture negative—up to 50% in some case series—and because K. kingae bacteria are hard to identify without sophisticated laboratory tests not routinely used in the United States.

“It could be that if we were using PCR [polymerase chain reaction] rather than cultures, we'd be seeing a lot more,” he said.

Recovery of K. kingae is difficult because the gram-negative coccobacillus is hard to grow on culture, requires an enhanced isolation methodology, and takes a little longer than normal to grow, which may require laboratories to hold on to culture plates for up to 7 days.

Researchers in France have developed a specific real-time PCR method to detect K. kingae DNA, and prospectively applied it to the diagnosis of all pediatric admissions for osteoarticular infection between January 2004 and December 2005. With culture alone, a pathogen was identified in 45% of the 131 specimens, including S. aureus in 25, K. kingae in 17, and other organisms in 18 (Pediatr. Infect. Dis. J. 2007;26:377-81).

The combination of culture, plus 16S ribosomal DNA sequence PCR, improved documentation, identifying 16 additional K. kingae cases. The use of the K. kingae-specific PCR confirmed those 16 cases and identified a further 6 cases. Based on these results, K. kingae was the leading cause of osteoarticular infection (39 cases), followed by S. aureus (25 cases).

“PCR for Kingella is not set up at our place or many others now,” Dr. Kaplan said in an interview. “PCR for Kingella is mainly research at the moment, but is something that will be set up in the future.”

Treatment of culture-negative osteomyelitis is equally challenging in the current era of rising community-associated MRSA infections and clindamycin resistance, said Dr. Kaplan, also professor of pediatrics at Baylor College of Medicine, Houston. K. kingae bacteria are resistant to clindamycin, vancomycin, and trimethoprim/sulfamethoxazole, drugs that are currently active against most community-associated MRSA isolates.

If a patient does not respond to initial therapy directed against S. aureus, including community-associated MRSA, renew efforts to obtain specimens for culture and consider expanding therapy to include K. kingae, clindamycin-resistant S. aureus, as well as other organisms based on the patient's exposure history, he said.

It also might not be a bad idea to hold on to culture plates a little longer, Dr. Kaplan advised.

At left, an x-ray of an 18-month-old patient showed a lytic lesion (arrow) of the distal epiphysis of the femur. At top right, a micrograph of an extracted isolate shows a gram-negative bacillus (arrow). At bottom right, a micrograph shows a growth of Kingella kingae, which may take up to 7 days to culture. Images courtesy Sarah S. Long/©2008 Elsevier Inc.

CHICAGO — Triamcinolone acetonide 10 mg/mL is the best dose for psoriatic fingernails dystrophy, according to a randomized, dose-comparison study.

The 90 psoriatic fingernails included in the study were divided into three groups of 30 and treated with an intramatrix injection of triamcinolone acetonide 2.5 mg/mL (group A), 5 mg/mL (group B), or 10 mg/mL (group C), reported Dr. Savreet Kaur and Dr. Karan Jit Pal Singh Puri. Treatment was repeated at 6 and 12 weeks. Assessment was done using the Nail Psoriasis Severity Index, with a grade IV change defined as more than a 75% improvement.

The study included 32 patients (aged 17–62 years). At 6 months, a grade IV improvement was observed in group A, B, and C in pitting in 27%, 78.5%, and 83% of nails, respectively; onycholysis (12.5%, 46%, and 53%); subungual hyperkeratosis (36%, 33%, and 59%); discoloration (33%, 44%, and 71%); and crumbling (0%, 50%, and 92%), the researchers noted in a poster at the annual meeting of the American Academy of Dermatology's Academy.

Dr. Kaur is at the Civil Hospital Khanna, in Punjab, India, and Dr. Puri is head of the department of dermatology, venereology, and leprosy at the Government Medical College, in Amritsar, India. They reported no conflicts of interest.

CHICAGO — Triamcinolone acetonide 10 mg/mL is the best dose for psoriatic fingernails dystrophy, according to a randomized, dose-comparison study.

The 90 psoriatic fingernails included in the study were divided into three groups of 30 and treated with an intramatrix injection of triamcinolone acetonide 2.5 mg/mL (group A), 5 mg/mL (group B), or 10 mg/mL (group C), reported Dr. Savreet Kaur and Dr. Karan Jit Pal Singh Puri. Treatment was repeated at 6 and 12 weeks. Assessment was done using the Nail Psoriasis Severity Index, with a grade IV change defined as more than a 75% improvement.

The study included 32 patients (aged 17–62 years). At 6 months, a grade IV improvement was observed in group A, B, and C in pitting in 27%, 78.5%, and 83% of nails, respectively; onycholysis (12.5%, 46%, and 53%); subungual hyperkeratosis (36%, 33%, and 59%); discoloration (33%, 44%, and 71%); and crumbling (0%, 50%, and 92%), the researchers noted in a poster at the annual meeting of the American Academy of Dermatology's Academy.

Dr. Kaur is at the Civil Hospital Khanna, in Punjab, India, and Dr. Puri is head of the department of dermatology, venereology, and leprosy at the Government Medical College, in Amritsar, India. They reported no conflicts of interest.

CHICAGO — Triamcinolone acetonide 10 mg/mL is the best dose for psoriatic fingernails dystrophy, according to a randomized, dose-comparison study.

The 90 psoriatic fingernails included in the study were divided into three groups of 30 and treated with an intramatrix injection of triamcinolone acetonide 2.5 mg/mL (group A), 5 mg/mL (group B), or 10 mg/mL (group C), reported Dr. Savreet Kaur and Dr. Karan Jit Pal Singh Puri. Treatment was repeated at 6 and 12 weeks. Assessment was done using the Nail Psoriasis Severity Index, with a grade IV change defined as more than a 75% improvement.

The study included 32 patients (aged 17–62 years). At 6 months, a grade IV improvement was observed in group A, B, and C in pitting in 27%, 78.5%, and 83% of nails, respectively; onycholysis (12.5%, 46%, and 53%); subungual hyperkeratosis (36%, 33%, and 59%); discoloration (33%, 44%, and 71%); and crumbling (0%, 50%, and 92%), the researchers noted in a poster at the annual meeting of the American Academy of Dermatology's Academy.

Dr. Kaur is at the Civil Hospital Khanna, in Punjab, India, and Dr. Puri is head of the department of dermatology, venereology, and leprosy at the Government Medical College, in Amritsar, India. They reported no conflicts of interest.

STOCKHOLM — Vaccination coverage for very severe manifestations of influenza remains low in patients with cancer, even though they are at high risk.

Just 34% of 112 consecutive cancer patients receiving treatment at the Hôpital Cochin, Paris, also received flu shots in 2008. Of these, 14% had chemotherapy as their only indication for vaccination, and 44% had other indications such as bronchopathy and diabetes.

The main reasons for absence of vaccination were lack of prompting by the treating physician (72%), fear of side effects (33%), and concerns about vaccine efficacy (10%), Dr. Pierre Loulergue reported in an award-winning poster at the European Society of Medical Oncology Congress.

General practitioners administered the flu shots in 56% of vaccinated patients. “The GP could do 100% of vaccinations,” Dr. Loulergue said in an interview. “But the oncologist must be more aware of the necessity to vaccinate.”

Dr. Loulergue said if cancer patients have influenza, the consequences can be more severe and can delay chemotherapy. Guidelines in France and in the United States recommend vaccination against influenza in all immunocompromised patients. However, the leading reason cited by oncologists for not giving the flu shot was the lack of awareness of recommendations.

In a previous study, one-third of 214 radiotherapy patients (aged 50 years or older) at the University of Pennsylvania, Philadelphia, said they never had an annual flu shot. Only 7% said a cancer specialist discussed vaccinations with them, compared with 44% of general practitioners (FAMILY PRACTICE NEWS, Dec. 1, 2007, p. 18).

Studies have also suggested lower influenza vaccination immunogenicity in chemotherapy patients, Dr. Loulergue said. The investigators hope to address immunogenicity in a follow-up study.

In the current study, patients (aged 16–87 years) had received chemotherapy for a median time of 7 months (range, 1–41 months). Indications included colorectal (21%), lung (16%), prostate (15%), sarcoma (8%), and urothelial (7%) cancer.

Vaccinated patients were significantly older than those not vaccinated (70 vs. 59 years) and were more likely to have received a vaccination voucher from the French national health insurance agency (71% vs. 36%). The researchers reported no conflicts of interest.

Oncologists should be more aware of the necessity to vaccinate patients who have cancer. DR. LOULERGUE

STOCKHOLM — Vaccination coverage for very severe manifestations of influenza remains low in patients with cancer, even though they are at high risk.

Just 34% of 112 consecutive cancer patients receiving treatment at the Hôpital Cochin, Paris, also received flu shots in 2008. Of these, 14% had chemotherapy as their only indication for vaccination, and 44% had other indications such as bronchopathy and diabetes.

The main reasons for absence of vaccination were lack of prompting by the treating physician (72%), fear of side effects (33%), and concerns about vaccine efficacy (10%), Dr. Pierre Loulergue reported in an award-winning poster at the European Society of Medical Oncology Congress.

General practitioners administered the flu shots in 56% of vaccinated patients. “The GP could do 100% of vaccinations,” Dr. Loulergue said in an interview. “But the oncologist must be more aware of the necessity to vaccinate.”

Dr. Loulergue said if cancer patients have influenza, the consequences can be more severe and can delay chemotherapy. Guidelines in France and in the United States recommend vaccination against influenza in all immunocompromised patients. However, the leading reason cited by oncologists for not giving the flu shot was the lack of awareness of recommendations.

In a previous study, one-third of 214 radiotherapy patients (aged 50 years or older) at the University of Pennsylvania, Philadelphia, said they never had an annual flu shot. Only 7% said a cancer specialist discussed vaccinations with them, compared with 44% of general practitioners (FAMILY PRACTICE NEWS, Dec. 1, 2007, p. 18).

Studies have also suggested lower influenza vaccination immunogenicity in chemotherapy patients, Dr. Loulergue said. The investigators hope to address immunogenicity in a follow-up study.

In the current study, patients (aged 16–87 years) had received chemotherapy for a median time of 7 months (range, 1–41 months). Indications included colorectal (21%), lung (16%), prostate (15%), sarcoma (8%), and urothelial (7%) cancer.

Vaccinated patients were significantly older than those not vaccinated (70 vs. 59 years) and were more likely to have received a vaccination voucher from the French national health insurance agency (71% vs. 36%). The researchers reported no conflicts of interest.

Oncologists should be more aware of the necessity to vaccinate patients who have cancer. DR. LOULERGUE

STOCKHOLM — Vaccination coverage for very severe manifestations of influenza remains low in patients with cancer, even though they are at high risk.

Just 34% of 112 consecutive cancer patients receiving treatment at the Hôpital Cochin, Paris, also received flu shots in 2008. Of these, 14% had chemotherapy as their only indication for vaccination, and 44% had other indications such as bronchopathy and diabetes.

The main reasons for absence of vaccination were lack of prompting by the treating physician (72%), fear of side effects (33%), and concerns about vaccine efficacy (10%), Dr. Pierre Loulergue reported in an award-winning poster at the European Society of Medical Oncology Congress.

General practitioners administered the flu shots in 56% of vaccinated patients. “The GP could do 100% of vaccinations,” Dr. Loulergue said in an interview. “But the oncologist must be more aware of the necessity to vaccinate.”

Dr. Loulergue said if cancer patients have influenza, the consequences can be more severe and can delay chemotherapy. Guidelines in France and in the United States recommend vaccination against influenza in all immunocompromised patients. However, the leading reason cited by oncologists for not giving the flu shot was the lack of awareness of recommendations.

In a previous study, one-third of 214 radiotherapy patients (aged 50 years or older) at the University of Pennsylvania, Philadelphia, said they never had an annual flu shot. Only 7% said a cancer specialist discussed vaccinations with them, compared with 44% of general practitioners (FAMILY PRACTICE NEWS, Dec. 1, 2007, p. 18).

Studies have also suggested lower influenza vaccination immunogenicity in chemotherapy patients, Dr. Loulergue said. The investigators hope to address immunogenicity in a follow-up study.

In the current study, patients (aged 16–87 years) had received chemotherapy for a median time of 7 months (range, 1–41 months). Indications included colorectal (21%), lung (16%), prostate (15%), sarcoma (8%), and urothelial (7%) cancer.

Vaccinated patients were significantly older than those not vaccinated (70 vs. 59 years) and were more likely to have received a vaccination voucher from the French national health insurance agency (71% vs. 36%). The researchers reported no conflicts of interest.

Oncologists should be more aware of the necessity to vaccinate patients who have cancer. DR. LOULERGUE

CHICAGO – In a group of patients with motor fluctuations and dopamine agonist-related side effects, adding orally disintegrating selegiline and decreasing the dopamine agonist dose reduced these adverse events without worsening Parkinson's disease symptoms.

According to self-reports from the first 50 patients in a 12-week, multicenter, open-label study, daytime sleepiness (defined as a score greater than 10 on the Epworth Sleepiness Scale) was present in 41 patients at baseline and, of those, was reduced in 28 (68%) and resolved in an additional 9 (22%) at study completion.

Symptoms were also reduced or resolved for 14 patients with hallucinations (36% reduced, 57% resolved), 22 patients with pedal edema (46% reduced, 23% resolved), and 23 patients with impulsive behavior including gambling, sexual urges, eating, and buying (48% reduced, 35% resolved), Dr. Rajesh Pahwa reported on behalf of the investigators of the A to Z Study in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS) were not significantly different at baseline and week 12, reported Dr. Pahwa, who serves as director of the Parkinson's disease and movement disorder center at the University of Kansas Medical Center, Kansas City.

However, Dr. Pahwah and colleagues found that significant reductions from baseline were observed in the UPDRS activities of daily living scores (11.9 at baseline vs. 10.2 at week 12) and mentation scores (2.4 at baseline vs. 1.9 at week 12).

Orally disintegrating selegiline (Zelapar) is indicated as adjunctive therapy in Parkinson's disease patients who exhibit deterioration in their response to levodopa. There is no evidence from controlled trials that the monoamine oxidase type B inhibitor has any beneficial effect in the absence of concurrent levodopa therapy.

Patients in the study had idiopathic Parkinson's disease with levodopa-induced motor fluctuations that required reductions in the dopamine agonist (DA) dosage because of adverse events. In Dr. Pahwa's clinical experience, the addition of orally disintegrating selegiline in such patients has reduced the side effects of DA because it allows for a reduction in DA dose.

“I proposed the study based on my clinical experience with dopamine agonists and Zelapar, and the results of the study confirmed my clinical experience,” Dr. Pahwa said in an interview.

About 25%-30% of patients treated with DAs experience somnolence; 40% have pedal edema, 15%-20% have hallucinations, and 5% have impulse disorders, he said.

At baseline, 29 (58%) of the first 50 patients in the study were taking pramipexole (mean dosage, 2.3 mg/day) and 21 (42%) were taking ropinirole (mean dosage, 10.6 mg/day).

The final mean pramipexole dosage was 0.5 mg/day and the mean ropinirole dosage was 3.0 mg/day.

The DA dosage was cut in half within 1 week of baseline, and orally disintegrating selegiline (1.25 mg once daily) was added. At week 3, if DA-related adverse events persisted and efficacy was unchanged, the DA dosage was tapered to discontinuation, and orally disintegrating selegiline was continued. At week 6, orally disintegrating selegiline was increased to 2.5 mg/day.

If the DA dosage was not discontinued and DA-related adverse events were still present with efficacy unchanged, the DA dosage was further reduced. At the final visit, 44 patients were taking 2.5 mg/day orally disintegrating selegiline, and 6 patients were taking 1.25 mg/day, according to Dr. Pahwa.

Adverse events were assessed at baseline and at weeks 3, 6, and 12 by self-report, as well as by the Epworth Sleepiness Scale, the Neuropsychiatric Inventory, the Barratt Impulsiveness Scale, and ankle circumference.

The study was supported by Valeant Pharmaceuticals International, which markets Zelapar. Dr. Pahwa is a consultant and speaker for and has received research grants from Valeant, Boehringer Ingelheim GmbH, and GlaxoSmithKline.

CHICAGO – In a group of patients with motor fluctuations and dopamine agonist-related side effects, adding orally disintegrating selegiline and decreasing the dopamine agonist dose reduced these adverse events without worsening Parkinson's disease symptoms.

According to self-reports from the first 50 patients in a 12-week, multicenter, open-label study, daytime sleepiness (defined as a score greater than 10 on the Epworth Sleepiness Scale) was present in 41 patients at baseline and, of those, was reduced in 28 (68%) and resolved in an additional 9 (22%) at study completion.

Symptoms were also reduced or resolved for 14 patients with hallucinations (36% reduced, 57% resolved), 22 patients with pedal edema (46% reduced, 23% resolved), and 23 patients with impulsive behavior including gambling, sexual urges, eating, and buying (48% reduced, 35% resolved), Dr. Rajesh Pahwa reported on behalf of the investigators of the A to Z Study in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS) were not significantly different at baseline and week 12, reported Dr. Pahwa, who serves as director of the Parkinson's disease and movement disorder center at the University of Kansas Medical Center, Kansas City.

However, Dr. Pahwah and colleagues found that significant reductions from baseline were observed in the UPDRS activities of daily living scores (11.9 at baseline vs. 10.2 at week 12) and mentation scores (2.4 at baseline vs. 1.9 at week 12).

Orally disintegrating selegiline (Zelapar) is indicated as adjunctive therapy in Parkinson's disease patients who exhibit deterioration in their response to levodopa. There is no evidence from controlled trials that the monoamine oxidase type B inhibitor has any beneficial effect in the absence of concurrent levodopa therapy.

Patients in the study had idiopathic Parkinson's disease with levodopa-induced motor fluctuations that required reductions in the dopamine agonist (DA) dosage because of adverse events. In Dr. Pahwa's clinical experience, the addition of orally disintegrating selegiline in such patients has reduced the side effects of DA because it allows for a reduction in DA dose.

“I proposed the study based on my clinical experience with dopamine agonists and Zelapar, and the results of the study confirmed my clinical experience,” Dr. Pahwa said in an interview.

About 25%-30% of patients treated with DAs experience somnolence; 40% have pedal edema, 15%-20% have hallucinations, and 5% have impulse disorders, he said.

At baseline, 29 (58%) of the first 50 patients in the study were taking pramipexole (mean dosage, 2.3 mg/day) and 21 (42%) were taking ropinirole (mean dosage, 10.6 mg/day).

The final mean pramipexole dosage was 0.5 mg/day and the mean ropinirole dosage was 3.0 mg/day.

The DA dosage was cut in half within 1 week of baseline, and orally disintegrating selegiline (1.25 mg once daily) was added. At week 3, if DA-related adverse events persisted and efficacy was unchanged, the DA dosage was tapered to discontinuation, and orally disintegrating selegiline was continued. At week 6, orally disintegrating selegiline was increased to 2.5 mg/day.

If the DA dosage was not discontinued and DA-related adverse events were still present with efficacy unchanged, the DA dosage was further reduced. At the final visit, 44 patients were taking 2.5 mg/day orally disintegrating selegiline, and 6 patients were taking 1.25 mg/day, according to Dr. Pahwa.

Adverse events were assessed at baseline and at weeks 3, 6, and 12 by self-report, as well as by the Epworth Sleepiness Scale, the Neuropsychiatric Inventory, the Barratt Impulsiveness Scale, and ankle circumference.

The study was supported by Valeant Pharmaceuticals International, which markets Zelapar. Dr. Pahwa is a consultant and speaker for and has received research grants from Valeant, Boehringer Ingelheim GmbH, and GlaxoSmithKline.

CHICAGO – In a group of patients with motor fluctuations and dopamine agonist-related side effects, adding orally disintegrating selegiline and decreasing the dopamine agonist dose reduced these adverse events without worsening Parkinson's disease symptoms.

According to self-reports from the first 50 patients in a 12-week, multicenter, open-label study, daytime sleepiness (defined as a score greater than 10 on the Epworth Sleepiness Scale) was present in 41 patients at baseline and, of those, was reduced in 28 (68%) and resolved in an additional 9 (22%) at study completion.

Symptoms were also reduced or resolved for 14 patients with hallucinations (36% reduced, 57% resolved), 22 patients with pedal edema (46% reduced, 23% resolved), and 23 patients with impulsive behavior including gambling, sexual urges, eating, and buying (48% reduced, 35% resolved), Dr. Rajesh Pahwa reported on behalf of the investigators of the A to Z Study in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS) were not significantly different at baseline and week 12, reported Dr. Pahwa, who serves as director of the Parkinson's disease and movement disorder center at the University of Kansas Medical Center, Kansas City.

However, Dr. Pahwah and colleagues found that significant reductions from baseline were observed in the UPDRS activities of daily living scores (11.9 at baseline vs. 10.2 at week 12) and mentation scores (2.4 at baseline vs. 1.9 at week 12).

Orally disintegrating selegiline (Zelapar) is indicated as adjunctive therapy in Parkinson's disease patients who exhibit deterioration in their response to levodopa. There is no evidence from controlled trials that the monoamine oxidase type B inhibitor has any beneficial effect in the absence of concurrent levodopa therapy.

Patients in the study had idiopathic Parkinson's disease with levodopa-induced motor fluctuations that required reductions in the dopamine agonist (DA) dosage because of adverse events. In Dr. Pahwa's clinical experience, the addition of orally disintegrating selegiline in such patients has reduced the side effects of DA because it allows for a reduction in DA dose.

“I proposed the study based on my clinical experience with dopamine agonists and Zelapar, and the results of the study confirmed my clinical experience,” Dr. Pahwa said in an interview.

About 25%-30% of patients treated with DAs experience somnolence; 40% have pedal edema, 15%-20% have hallucinations, and 5% have impulse disorders, he said.

At baseline, 29 (58%) of the first 50 patients in the study were taking pramipexole (mean dosage, 2.3 mg/day) and 21 (42%) were taking ropinirole (mean dosage, 10.6 mg/day).

The final mean pramipexole dosage was 0.5 mg/day and the mean ropinirole dosage was 3.0 mg/day.

The DA dosage was cut in half within 1 week of baseline, and orally disintegrating selegiline (1.25 mg once daily) was added. At week 3, if DA-related adverse events persisted and efficacy was unchanged, the DA dosage was tapered to discontinuation, and orally disintegrating selegiline was continued. At week 6, orally disintegrating selegiline was increased to 2.5 mg/day.

If the DA dosage was not discontinued and DA-related adverse events were still present with efficacy unchanged, the DA dosage was further reduced. At the final visit, 44 patients were taking 2.5 mg/day orally disintegrating selegiline, and 6 patients were taking 1.25 mg/day, according to Dr. Pahwa.

Adverse events were assessed at baseline and at weeks 3, 6, and 12 by self-report, as well as by the Epworth Sleepiness Scale, the Neuropsychiatric Inventory, the Barratt Impulsiveness Scale, and ankle circumference.

The study was supported by Valeant Pharmaceuticals International, which markets Zelapar. Dr. Pahwa is a consultant and speaker for and has received research grants from Valeant, Boehringer Ingelheim GmbH, and GlaxoSmithKline.

CHICAGO — The value of probiotics in atopic disease remains controversial, but clues are beginning to emerge in the literature about probiotics' role in treatment and prevention.

Dr. Sharon S. Raimer highlighted the conflicting trail of evidence surrounding probiotic supplementation for the prevention and treatment of pediatric atopic dermatitis (AD) at a meeting sponsored by the American Academy of Pediatrics.

"It looks like at the present time that probiotics are really not very good for treatment, but they might help in prevention; but you have to give the probiotic prenatally for it to really work," said Dr. Raimer, chair of dermatology, University of Texas at Galveston.

These considerations are largely based on a recent meta-analysis of six prevention and four treatment double-blind randomized controlled trials of probiotics and pediatric AD (J. Allergy Clin. Immunol. 2008;121: 116–21).

The analysis identified a significant risk reduction—by as much as 61%—associated with the use of prenatal and/or postnatal probiotics for primary pediatric AD prevention among 1,581 participants, but only a marginal effect of treatment among 299 participants.

Such meta-analyses are complicated by the variety of bacteria strains and strengths studied, Dr. Raimer said.

Probiotic trials also typically have small sample sizes and heterogeneity of protocols, and might not assess for use of potential confounders such as concomitant antibiotics, topical corticosteroids, and antigen- eliminating diets.

An early trial supporting the role of probiotics in allergy prevention randomized mothers with a family history of atopic eczema, allergic rhinitis, or asthma to two capsules containing placebo or 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG daily for 2–4 weeks before date of delivery.

After delivery, breastfeeding mothers were given the capsules, while infants who were not breastfed were given the capsule contents mixed with water, for 6 months.

Atopic eczema was diagnosed in 46 of 132 (35%) children at 2 years of age, with the frequency of eczema in the probiotic group half that of the placebo group (23% vs. 46%) (Lancet 2001;357:1076–9).

A follow-up study of these at-risk children revealed that 14 of 53 (26%) receiving Lactobacillus had developed atopic eczema at 4 years, compared with 25 of 54 (46%) receiving placebo (Lancet 2003;361:1869–71), suggesting that the preventive effect of Lactobacillus extends beyond infancy. Skin-prick test reactivity was found to be the same in both groups.

Early probiotic supplementation alone appears not to be beneficial in reducing the risk of AD and might actually increase the risk of allergen sensitization in high-risk children, said Dr. Raimer, also a professor of dermatology and pediatrics.

She cited an Australian study that found no difference in AD rates at 6 and 12 months between 177 infants who received Lactobacillus acidophilus or placebo for the first 6 months of life, and a significantly higher rate of sensitization to common allergens in the probiotic group at 12 months (Allergy Clin. Immunol. 2007;119:184–91).

Finally, a prospective randomized trial of supplementation during pregnancy and early infancy adds even more intrigue to the probiotic controversy.

Supplementation with 5 × 109 colony-forming units of Lactobacillus GG twice daily for 4–6 weeks before delivery and 6 months postnatally neither reduced the incidence of atopic eczema nor altered disease severity in AD affected children, but was associated with an increased rate of recurrent episodes of wheezing bronchitis in the study children (Pediatrics 2008;121:e850–6).

The German researchers concluded that Lactobacillus GG cannot be generally recommended for primary prevention of atopic eczema.

CHICAGO — The value of probiotics in atopic disease remains controversial, but clues are beginning to emerge in the literature about probiotics' role in treatment and prevention.

Dr. Sharon S. Raimer highlighted the conflicting trail of evidence surrounding probiotic supplementation for the prevention and treatment of pediatric atopic dermatitis (AD) at a meeting sponsored by the American Academy of Pediatrics.

"It looks like at the present time that probiotics are really not very good for treatment, but they might help in prevention; but you have to give the probiotic prenatally for it to really work," said Dr. Raimer, chair of dermatology, University of Texas at Galveston.

These considerations are largely based on a recent meta-analysis of six prevention and four treatment double-blind randomized controlled trials of probiotics and pediatric AD (J. Allergy Clin. Immunol. 2008;121: 116–21).

The analysis identified a significant risk reduction—by as much as 61%—associated with the use of prenatal and/or postnatal probiotics for primary pediatric AD prevention among 1,581 participants, but only a marginal effect of treatment among 299 participants.

Such meta-analyses are complicated by the variety of bacteria strains and strengths studied, Dr. Raimer said.

Probiotic trials also typically have small sample sizes and heterogeneity of protocols, and might not assess for use of potential confounders such as concomitant antibiotics, topical corticosteroids, and antigen- eliminating diets.

An early trial supporting the role of probiotics in allergy prevention randomized mothers with a family history of atopic eczema, allergic rhinitis, or asthma to two capsules containing placebo or 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG daily for 2–4 weeks before date of delivery.

After delivery, breastfeeding mothers were given the capsules, while infants who were not breastfed were given the capsule contents mixed with water, for 6 months.

Atopic eczema was diagnosed in 46 of 132 (35%) children at 2 years of age, with the frequency of eczema in the probiotic group half that of the placebo group (23% vs. 46%) (Lancet 2001;357:1076–9).

A follow-up study of these at-risk children revealed that 14 of 53 (26%) receiving Lactobacillus had developed atopic eczema at 4 years, compared with 25 of 54 (46%) receiving placebo (Lancet 2003;361:1869–71), suggesting that the preventive effect of Lactobacillus extends beyond infancy. Skin-prick test reactivity was found to be the same in both groups.

Early probiotic supplementation alone appears not to be beneficial in reducing the risk of AD and might actually increase the risk of allergen sensitization in high-risk children, said Dr. Raimer, also a professor of dermatology and pediatrics.

She cited an Australian study that found no difference in AD rates at 6 and 12 months between 177 infants who received Lactobacillus acidophilus or placebo for the first 6 months of life, and a significantly higher rate of sensitization to common allergens in the probiotic group at 12 months (Allergy Clin. Immunol. 2007;119:184–91).

Finally, a prospective randomized trial of supplementation during pregnancy and early infancy adds even more intrigue to the probiotic controversy.

Supplementation with 5 × 109 colony-forming units of Lactobacillus GG twice daily for 4–6 weeks before delivery and 6 months postnatally neither reduced the incidence of atopic eczema nor altered disease severity in AD affected children, but was associated with an increased rate of recurrent episodes of wheezing bronchitis in the study children (Pediatrics 2008;121:e850–6).

The German researchers concluded that Lactobacillus GG cannot be generally recommended for primary prevention of atopic eczema.

CHICAGO — The value of probiotics in atopic disease remains controversial, but clues are beginning to emerge in the literature about probiotics' role in treatment and prevention.

Dr. Sharon S. Raimer highlighted the conflicting trail of evidence surrounding probiotic supplementation for the prevention and treatment of pediatric atopic dermatitis (AD) at a meeting sponsored by the American Academy of Pediatrics.

"It looks like at the present time that probiotics are really not very good for treatment, but they might help in prevention; but you have to give the probiotic prenatally for it to really work," said Dr. Raimer, chair of dermatology, University of Texas at Galveston.

These considerations are largely based on a recent meta-analysis of six prevention and four treatment double-blind randomized controlled trials of probiotics and pediatric AD (J. Allergy Clin. Immunol. 2008;121: 116–21).

The analysis identified a significant risk reduction—by as much as 61%—associated with the use of prenatal and/or postnatal probiotics for primary pediatric AD prevention among 1,581 participants, but only a marginal effect of treatment among 299 participants.

Such meta-analyses are complicated by the variety of bacteria strains and strengths studied, Dr. Raimer said.

Probiotic trials also typically have small sample sizes and heterogeneity of protocols, and might not assess for use of potential confounders such as concomitant antibiotics, topical corticosteroids, and antigen- eliminating diets.

An early trial supporting the role of probiotics in allergy prevention randomized mothers with a family history of atopic eczema, allergic rhinitis, or asthma to two capsules containing placebo or 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG daily for 2–4 weeks before date of delivery.

After delivery, breastfeeding mothers were given the capsules, while infants who were not breastfed were given the capsule contents mixed with water, for 6 months.

Atopic eczema was diagnosed in 46 of 132 (35%) children at 2 years of age, with the frequency of eczema in the probiotic group half that of the placebo group (23% vs. 46%) (Lancet 2001;357:1076–9).

A follow-up study of these at-risk children revealed that 14 of 53 (26%) receiving Lactobacillus had developed atopic eczema at 4 years, compared with 25 of 54 (46%) receiving placebo (Lancet 2003;361:1869–71), suggesting that the preventive effect of Lactobacillus extends beyond infancy. Skin-prick test reactivity was found to be the same in both groups.

Early probiotic supplementation alone appears not to be beneficial in reducing the risk of AD and might actually increase the risk of allergen sensitization in high-risk children, said Dr. Raimer, also a professor of dermatology and pediatrics.

She cited an Australian study that found no difference in AD rates at 6 and 12 months between 177 infants who received Lactobacillus acidophilus or placebo for the first 6 months of life, and a significantly higher rate of sensitization to common allergens in the probiotic group at 12 months (Allergy Clin. Immunol. 2007;119:184–91).

Finally, a prospective randomized trial of supplementation during pregnancy and early infancy adds even more intrigue to the probiotic controversy.

Supplementation with 5 × 109 colony-forming units of Lactobacillus GG twice daily for 4–6 weeks before delivery and 6 months postnatally neither reduced the incidence of atopic eczema nor altered disease severity in AD affected children, but was associated with an increased rate of recurrent episodes of wheezing bronchitis in the study children (Pediatrics 2008;121:e850–6).

The German researchers concluded that Lactobacillus GG cannot be generally recommended for primary prevention of atopic eczema.

CHICAGO — Despite bone-chilling temperatures and the risk of frostbite, patients who underwent experimental whole-body cryotherapy for atopic dermatitis said they were willing to do it again.

This Finnish experience with whole-body cryotherapy was just one of three "outside-the-box" treatments for atopic dermatitis to emerge in recent months and was highlighted by Dr. Albert C. Yan, chief of the dermatology section at Children's Hospital of Philadelphia, during an atopic dermatitis symposium at the American Academy of Dermatology Academy 2008 summer meeting.

▸ Whole-body cryotherapy. This therapy has been used to treat rheumatic inflammation and pain since the 1970s. The rationale for the therapy in atopic dermatitis is based on reports that very cold air increases the body's antioxidative capacity and reduces the conduction velocity of peripheral nerves and the nerve ganglia capacity to synthesize acetylcholine, which is considered a neurotransmitter in atopic pruritus, according to Dr. Yan.

Investigators at the Skin and Allergy Hospital in Helsinki applied whole-body cryotherapy to 18 adults with mild to moderate atopic dermatitis three times a week for 4 weeks, followed by an 8-week follow-up period.

Topical anti-inflammatory preparations or systemic antihistamines were not allowed for 1 week before or at any time during the study, and there was a 6-week washout period for systemic therapy and phototherapy.

The Univers Cryo-Combi whole-body cryotherapy device (Oy MJG Univers Ab, Helsinki) consists of two precooling chambers set at −30° C and −60° C, where patients remained for a very short time, and a third chamber that reaches −110° C, where patients remained for 1 to 3 minutes wearing a bathing suit or trunks, with acral parts covered.

The study's primary end point of change in the Scoring of Atopic Dermatitis (SCORAD) index (scale 0–103) decreased almost 20% from 38.7 to 31.1 (Arch. Dermatol. 2008;144:806–8).

Pruritus, sleep loss, and SCORAD rating tended to improve after the 4 weeks of treatment.

Three patients had treatment-related adverse events, all mild acral frostbite. Sixteen of the 18 patients completed therapy, an average of 11 sessions (range from 9 to 12 sessions).

One patient left the study because of worsening dermatitis, and another left because of work schedule. All patients were willing to undergo further treatment.

The device used in the study is the first to use both liquid nitrogen and compressor technology to produce cold air. This maintains an optimal oxygen level of 22% in the chamber that allows even patients with asthma to undergo the treatment, according to lead author Dr. Taras Klimenko and colleagues, who reported no conflicts of interest.

The study was supported by grants from The Finnish Society of Dermatology and The Finnish Society of Dermatopathology.

▸ Vitamin D supplementation. Supplements of vitamin D helped improve wintertime onset or exacerbation of atopic dermatitis in children aged 2–13 years who were randomized to oral ergocalciferol 1000 IU in a double-blind, pilot study (Br. J. Dermatol. 2008;159:245–7).

The Investigator's Global Assessment—based on six categories, ranging from clear (1) to very severe (6)—improved by one category in four (80%) of five children on vitamin D versus one (17%) of six children on placebo. Similar improvements were seen in Eczema Area and Severity Index scores.

Lead author Dr. Robert Sidbury of Children's Hospital Boston and his associates suggested that the favorable impact of vitamin D on atopic dermatitis is biologically plausible.

The active form of vitamin D, 1,25-dihydroxyvitamin D₃, induces expression of antimicrobial peptides that help prevent skin infection and possess immunosuppressive properties in the skin. Recent research also has drawn attention to the connection between vitamin D-mediated activation of toll-like receptors, production of the antimicrobial peptide cathelicidin, and human susceptibility to bacterial infection.

"Thus, vitamin D deficiency could contribute to the hallmark signs of AD: altered barrier function, immune dysregulation, and inadequate bacterial defence," wrote the authors, who reported no conflicts of interest.

The study was supported by a grant from the Massachusetts General Hospital Center for D-receptor Activation Research in Boston.

▸ Rosiglitazone maleate. Used as an add-on therapy at doses of 2–4 mg twice daily, rosiglitazone (Avandia) was associated with increased control of severe atopic dermatitis in 6 patients nonresponsive to first- and second-line therapies, according to a retrospective review (Arch. Dermatol. 2008;144:84–8).

The six patients, aged 16–75 years, showed decreased extent of the disease, of inflammation, and of number of flares. In addition, rosiglitazone, which is indicated for the treatment of type II diabetes, allowed for gradual reduction or elimination of systemic steroids in the three patients who used them.

Major clinical improvement appeared between weeks 4 and 12, which suggests that some patients may require at least 3 months for a clinical response, according to lead author Ramona Behshad, principal investigator Dr. Kevin Cooper, and senior author Dr. Neil Korman, all of whom are with Case University, Cleveland.

No serious adverse events were seen in the study patients. The investigators suggested rosiglitazone may serve as a "good alternative to current systemic immunosuppressants used for severe AD," but urged caution in interpreting the promising results because of study design limitations and two previous randomized trials of rosiglitazone in psoriasis that failed to demonstrate any notable efficacy, compared with placebo.

The study was supported in part by the National Institute of Arthritis and Case Medical Center.

No financial disclosures were reported by the authors.

CHICAGO — Despite bone-chilling temperatures and the risk of frostbite, patients who underwent experimental whole-body cryotherapy for atopic dermatitis said they were willing to do it again.

This Finnish experience with whole-body cryotherapy was just one of three "outside-the-box" treatments for atopic dermatitis to emerge in recent months and was highlighted by Dr. Albert C. Yan, chief of the dermatology section at Children's Hospital of Philadelphia, during an atopic dermatitis symposium at the American Academy of Dermatology Academy 2008 summer meeting.

▸ Whole-body cryotherapy. This therapy has been used to treat rheumatic inflammation and pain since the 1970s. The rationale for the therapy in atopic dermatitis is based on reports that very cold air increases the body's antioxidative capacity and reduces the conduction velocity of peripheral nerves and the nerve ganglia capacity to synthesize acetylcholine, which is considered a neurotransmitter in atopic pruritus, according to Dr. Yan.

Investigators at the Skin and Allergy Hospital in Helsinki applied whole-body cryotherapy to 18 adults with mild to moderate atopic dermatitis three times a week for 4 weeks, followed by an 8-week follow-up period.

Topical anti-inflammatory preparations or systemic antihistamines were not allowed for 1 week before or at any time during the study, and there was a 6-week washout period for systemic therapy and phototherapy.

The Univers Cryo-Combi whole-body cryotherapy device (Oy MJG Univers Ab, Helsinki) consists of two precooling chambers set at −30° C and −60° C, where patients remained for a very short time, and a third chamber that reaches −110° C, where patients remained for 1 to 3 minutes wearing a bathing suit or trunks, with acral parts covered.

The study's primary end point of change in the Scoring of Atopic Dermatitis (SCORAD) index (scale 0–103) decreased almost 20% from 38.7 to 31.1 (Arch. Dermatol. 2008;144:806–8).

Pruritus, sleep loss, and SCORAD rating tended to improve after the 4 weeks of treatment.

Three patients had treatment-related adverse events, all mild acral frostbite. Sixteen of the 18 patients completed therapy, an average of 11 sessions (range from 9 to 12 sessions).

One patient left the study because of worsening dermatitis, and another left because of work schedule. All patients were willing to undergo further treatment.

The device used in the study is the first to use both liquid nitrogen and compressor technology to produce cold air. This maintains an optimal oxygen level of 22% in the chamber that allows even patients with asthma to undergo the treatment, according to lead author Dr. Taras Klimenko and colleagues, who reported no conflicts of interest.

The study was supported by grants from The Finnish Society of Dermatology and The Finnish Society of Dermatopathology.

▸ Vitamin D supplementation. Supplements of vitamin D helped improve wintertime onset or exacerbation of atopic dermatitis in children aged 2–13 years who were randomized to oral ergocalciferol 1000 IU in a double-blind, pilot study (Br. J. Dermatol. 2008;159:245–7).

The Investigator's Global Assessment—based on six categories, ranging from clear (1) to very severe (6)—improved by one category in four (80%) of five children on vitamin D versus one (17%) of six children on placebo. Similar improvements were seen in Eczema Area and Severity Index scores.

Lead author Dr. Robert Sidbury of Children's Hospital Boston and his associates suggested that the favorable impact of vitamin D on atopic dermatitis is biologically plausible.

The active form of vitamin D, 1,25-dihydroxyvitamin D₃, induces expression of antimicrobial peptides that help prevent skin infection and possess immunosuppressive properties in the skin. Recent research also has drawn attention to the connection between vitamin D-mediated activation of toll-like receptors, production of the antimicrobial peptide cathelicidin, and human susceptibility to bacterial infection.

"Thus, vitamin D deficiency could contribute to the hallmark signs of AD: altered barrier function, immune dysregulation, and inadequate bacterial defence," wrote the authors, who reported no conflicts of interest.

The study was supported by a grant from the Massachusetts General Hospital Center for D-receptor Activation Research in Boston.

▸ Rosiglitazone maleate. Used as an add-on therapy at doses of 2–4 mg twice daily, rosiglitazone (Avandia) was associated with increased control of severe atopic dermatitis in 6 patients nonresponsive to first- and second-line therapies, according to a retrospective review (Arch. Dermatol. 2008;144:84–8).

The six patients, aged 16–75 years, showed decreased extent of the disease, of inflammation, and of number of flares. In addition, rosiglitazone, which is indicated for the treatment of type II diabetes, allowed for gradual reduction or elimination of systemic steroids in the three patients who used them.

Major clinical improvement appeared between weeks 4 and 12, which suggests that some patients may require at least 3 months for a clinical response, according to lead author Ramona Behshad, principal investigator Dr. Kevin Cooper, and senior author Dr. Neil Korman, all of whom are with Case University, Cleveland.

No serious adverse events were seen in the study patients. The investigators suggested rosiglitazone may serve as a "good alternative to current systemic immunosuppressants used for severe AD," but urged caution in interpreting the promising results because of study design limitations and two previous randomized trials of rosiglitazone in psoriasis that failed to demonstrate any notable efficacy, compared with placebo.

The study was supported in part by the National Institute of Arthritis and Case Medical Center.

No financial disclosures were reported by the authors.

CHICAGO — Despite bone-chilling temperatures and the risk of frostbite, patients who underwent experimental whole-body cryotherapy for atopic dermatitis said they were willing to do it again.

This Finnish experience with whole-body cryotherapy was just one of three "outside-the-box" treatments for atopic dermatitis to emerge in recent months and was highlighted by Dr. Albert C. Yan, chief of the dermatology section at Children's Hospital of Philadelphia, during an atopic dermatitis symposium at the American Academy of Dermatology Academy 2008 summer meeting.

▸ Whole-body cryotherapy. This therapy has been used to treat rheumatic inflammation and pain since the 1970s. The rationale for the therapy in atopic dermatitis is based on reports that very cold air increases the body's antioxidative capacity and reduces the conduction velocity of peripheral nerves and the nerve ganglia capacity to synthesize acetylcholine, which is considered a neurotransmitter in atopic pruritus, according to Dr. Yan.

Investigators at the Skin and Allergy Hospital in Helsinki applied whole-body cryotherapy to 18 adults with mild to moderate atopic dermatitis three times a week for 4 weeks, followed by an 8-week follow-up period.

Topical anti-inflammatory preparations or systemic antihistamines were not allowed for 1 week before or at any time during the study, and there was a 6-week washout period for systemic therapy and phototherapy.

The Univers Cryo-Combi whole-body cryotherapy device (Oy MJG Univers Ab, Helsinki) consists of two precooling chambers set at −30° C and −60° C, where patients remained for a very short time, and a third chamber that reaches −110° C, where patients remained for 1 to 3 minutes wearing a bathing suit or trunks, with acral parts covered.

The study's primary end point of change in the Scoring of Atopic Dermatitis (SCORAD) index (scale 0–103) decreased almost 20% from 38.7 to 31.1 (Arch. Dermatol. 2008;144:806–8).

Pruritus, sleep loss, and SCORAD rating tended to improve after the 4 weeks of treatment.

Three patients had treatment-related adverse events, all mild acral frostbite. Sixteen of the 18 patients completed therapy, an average of 11 sessions (range from 9 to 12 sessions).

One patient left the study because of worsening dermatitis, and another left because of work schedule. All patients were willing to undergo further treatment.

The device used in the study is the first to use both liquid nitrogen and compressor technology to produce cold air. This maintains an optimal oxygen level of 22% in the chamber that allows even patients with asthma to undergo the treatment, according to lead author Dr. Taras Klimenko and colleagues, who reported no conflicts of interest.

The study was supported by grants from The Finnish Society of Dermatology and The Finnish Society of Dermatopathology.

▸ Vitamin D supplementation. Supplements of vitamin D helped improve wintertime onset or exacerbation of atopic dermatitis in children aged 2–13 years who were randomized to oral ergocalciferol 1000 IU in a double-blind, pilot study (Br. J. Dermatol. 2008;159:245–7).

The Investigator's Global Assessment—based on six categories, ranging from clear (1) to very severe (6)—improved by one category in four (80%) of five children on vitamin D versus one (17%) of six children on placebo. Similar improvements were seen in Eczema Area and Severity Index scores.

Lead author Dr. Robert Sidbury of Children's Hospital Boston and his associates suggested that the favorable impact of vitamin D on atopic dermatitis is biologically plausible.

The active form of vitamin D, 1,25-dihydroxyvitamin D₃, induces expression of antimicrobial peptides that help prevent skin infection and possess immunosuppressive properties in the skin. Recent research also has drawn attention to the connection between vitamin D-mediated activation of toll-like receptors, production of the antimicrobial peptide cathelicidin, and human susceptibility to bacterial infection.

"Thus, vitamin D deficiency could contribute to the hallmark signs of AD: altered barrier function, immune dysregulation, and inadequate bacterial defence," wrote the authors, who reported no conflicts of interest.

The study was supported by a grant from the Massachusetts General Hospital Center for D-receptor Activation Research in Boston.

▸ Rosiglitazone maleate. Used as an add-on therapy at doses of 2–4 mg twice daily, rosiglitazone (Avandia) was associated with increased control of severe atopic dermatitis in 6 patients nonresponsive to first- and second-line therapies, according to a retrospective review (Arch. Dermatol. 2008;144:84–8).

The six patients, aged 16–75 years, showed decreased extent of the disease, of inflammation, and of number of flares. In addition, rosiglitazone, which is indicated for the treatment of type II diabetes, allowed for gradual reduction or elimination of systemic steroids in the three patients who used them.

Major clinical improvement appeared between weeks 4 and 12, which suggests that some patients may require at least 3 months for a clinical response, according to lead author Ramona Behshad, principal investigator Dr. Kevin Cooper, and senior author Dr. Neil Korman, all of whom are with Case University, Cleveland.

No serious adverse events were seen in the study patients. The investigators suggested rosiglitazone may serve as a "good alternative to current systemic immunosuppressants used for severe AD," but urged caution in interpreting the promising results because of study design limitations and two previous randomized trials of rosiglitazone in psoriasis that failed to demonstrate any notable efficacy, compared with placebo.

The study was supported in part by the National Institute of Arthritis and Case Medical Center.

No financial disclosures were reported by the authors.

CHICAGO — The first large-scale trial of calcium hydroxylapatite in patients with Fitzpatrick skin types IV-VI showed no keloid formation, hypertropic scarring, or skin discoloration when used to treat nasolabial folds.

Although the reasons for scarring and keloids are not clear, anecdotally these side effects appear to present more in patients with darker skin types, lead investigator Dr. Ellen Marmur, chief of dermatologic surgery at Mount Sinai School of Medicine, New York, said in an interview.

"This study liberates many women and men with darker skin types to undergo cosmetic filler treatments with calcium hydroxylapatite," she said. "Past concerns about keloid scarring and discoloration now can be minimized, if not totally alleviated, for these patients.

"Their safety profiles matched those of the larger safety studies in lighter skin types showing this filler is safe to use in all skin types," she added.

The open-label, multicenter, nonrandomized prospective trial enrolled 100 patients with moderate to severe nasolabial folds and Fitzpatrick skin types IV (24%), V (35%), and VI (41%). Calcium hydroxylapatite 0.6 mL–2.8 mL (mean 1.24 mL) was injected subdermally with a 25- to 27-gauge needle using a linear threading/fanning technique.

The mean patient age was 52 years and 94 were female; 85% were African American, 12% were Hispanic, 2% were Asian, and 1%, other.

Evaluation of 100 patients at 3 months and 98 patients at 6 months revealed no keloid formation, hypertrophic scarring, hypopigmentation, hyperpigmentation, or other clinically significant adverse events, Dr. Marmur and her associates reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The study did not objectively evaluate efficacy, but treatment benefit, based on physician assessment, persisted for up to 6 months. Radiesse contains calcium-based microspheres suspended in a water-based gel that absorbs in 2–4 weeks, and builds volume by stimulating collagen growth around the implanted material.

Calcium hydroxylapatite (Radiesse) is approved for HIV-associated facial lipoatrophy, and is used as a cosmetic dermal filler.

The study was sponsored by BioForm Medical Inc., the maker of Radiesse. Dr. Marmur is on the medical education faculty for BioForm.

CHICAGO — The first large-scale trial of calcium hydroxylapatite in patients with Fitzpatrick skin types IV-VI showed no keloid formation, hypertropic scarring, or skin discoloration when used to treat nasolabial folds.

Although the reasons for scarring and keloids are not clear, anecdotally these side effects appear to present more in patients with darker skin types, lead investigator Dr. Ellen Marmur, chief of dermatologic surgery at Mount Sinai School of Medicine, New York, said in an interview.

"This study liberates many women and men with darker skin types to undergo cosmetic filler treatments with calcium hydroxylapatite," she said. "Past concerns about keloid scarring and discoloration now can be minimized, if not totally alleviated, for these patients.

"Their safety profiles matched those of the larger safety studies in lighter skin types showing this filler is safe to use in all skin types," she added.

The open-label, multicenter, nonrandomized prospective trial enrolled 100 patients with moderate to severe nasolabial folds and Fitzpatrick skin types IV (24%), V (35%), and VI (41%). Calcium hydroxylapatite 0.6 mL–2.8 mL (mean 1.24 mL) was injected subdermally with a 25- to 27-gauge needle using a linear threading/fanning technique.

The mean patient age was 52 years and 94 were female; 85% were African American, 12% were Hispanic, 2% were Asian, and 1%, other.

Evaluation of 100 patients at 3 months and 98 patients at 6 months revealed no keloid formation, hypertrophic scarring, hypopigmentation, hyperpigmentation, or other clinically significant adverse events, Dr. Marmur and her associates reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The study did not objectively evaluate efficacy, but treatment benefit, based on physician assessment, persisted for up to 6 months. Radiesse contains calcium-based microspheres suspended in a water-based gel that absorbs in 2–4 weeks, and builds volume by stimulating collagen growth around the implanted material.

Calcium hydroxylapatite (Radiesse) is approved for HIV-associated facial lipoatrophy, and is used as a cosmetic dermal filler.

The study was sponsored by BioForm Medical Inc., the maker of Radiesse. Dr. Marmur is on the medical education faculty for BioForm.

CHICAGO — The first large-scale trial of calcium hydroxylapatite in patients with Fitzpatrick skin types IV-VI showed no keloid formation, hypertropic scarring, or skin discoloration when used to treat nasolabial folds.

Although the reasons for scarring and keloids are not clear, anecdotally these side effects appear to present more in patients with darker skin types, lead investigator Dr. Ellen Marmur, chief of dermatologic surgery at Mount Sinai School of Medicine, New York, said in an interview.

"This study liberates many women and men with darker skin types to undergo cosmetic filler treatments with calcium hydroxylapatite," she said. "Past concerns about keloid scarring and discoloration now can be minimized, if not totally alleviated, for these patients.

"Their safety profiles matched those of the larger safety studies in lighter skin types showing this filler is safe to use in all skin types," she added.

The open-label, multicenter, nonrandomized prospective trial enrolled 100 patients with moderate to severe nasolabial folds and Fitzpatrick skin types IV (24%), V (35%), and VI (41%). Calcium hydroxylapatite 0.6 mL–2.8 mL (mean 1.24 mL) was injected subdermally with a 25- to 27-gauge needle using a linear threading/fanning technique.

The mean patient age was 52 years and 94 were female; 85% were African American, 12% were Hispanic, 2% were Asian, and 1%, other.

Evaluation of 100 patients at 3 months and 98 patients at 6 months revealed no keloid formation, hypertrophic scarring, hypopigmentation, hyperpigmentation, or other clinically significant adverse events, Dr. Marmur and her associates reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The study did not objectively evaluate efficacy, but treatment benefit, based on physician assessment, persisted for up to 6 months. Radiesse contains calcium-based microspheres suspended in a water-based gel that absorbs in 2–4 weeks, and builds volume by stimulating collagen growth around the implanted material.

Calcium hydroxylapatite (Radiesse) is approved for HIV-associated facial lipoatrophy, and is used as a cosmetic dermal filler.

The study was sponsored by BioForm Medical Inc., the maker of Radiesse. Dr. Marmur is on the medical education faculty for BioForm.

CHICAGO — Injectable poly-L-lactic acid used to treat nasolabial fold wrinkles produced significantly fewer overall product-related adverse events than human-derived collagen, study results have shown.

In a randomized multicenter trial of 233 patients with nasolabial fold wrinkles, the overall product-related adverse event rate was 21% with poly-L-lactic acid (PLLA; Sculptra) and 36% with human collagen (Cosmoplast), resulting in a P value of less than .05.

Compared with the PLLA group, the collagen group had more injection-site erythema (26.5% vs. 2.6%) and pruritus (8% vs. 1%), Dr. Marta Rendon and the Cosmetic Study Trial Group reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The PLLA group reported more injection-site pain (5.2% vs. 3.4%); more application-site papules, defined as palpable elevations less than 5 mm in diameter (8.6% vs. 3.4%); and more application-site nodules, defined as lesions 5 mm or more in diameter (7% vs. 6%). The difference between the groups was statistically significant for nodules.

The papules and nodules were nonvisible, palpable, and mild or moderate in intensity; all but one event resolved spontaneously during the 13-month follow-up period.

The frequency of adverse events with injectable PLLA, including injection-site pain, papules, and nodules, was lower than reported in early published reports in patients with HIV-related facial lipoatrophy, reported Dr. Rendon, who is in private practice in Boca Raton, Fla., and her associates.

No product-related serious adverse events occurred during the study, which was sponsored by Sanofi-Aventis U.S., which markets Sculptra in the United States through its subsidiary, Dermik Laboratories.

Injectable PLLA is currently approved in the United States for HIV-related facial lipoatrophy and is under review for volume restoration and/or correction of facial wrinkles and folds.

Patients (mean age 51 years) in the study had scores of 2–4 on a 5-point photo-numeric wrinkle assessment scale (WAS) for both the right and left nasolabial fold.

They underwent bilateral injections of PLLA (maximum 5 mL of reconstituted product per session) or collagen (1–2 cc per session) at one to four treatment sessions at 3-week intervals until an optimal correction was achieved for both folds. Roughly 40% in each group were Fitzpatrick skin type III.

Both the PLLA and collagen groups had significant reductions from baseline in WAS scores 3 weeks after the last treatment, as assessed by three plastic surgeons/dermatologists blinded to treatment.

Comparisons between the two groups in the change from baseline in mean WAS scores at subsequent time points resulted in significant differences favoring PLLA at months 3, 6, 9, and 13, reported Dr. Rendon and her associates.

CHICAGO — Injectable poly-L-lactic acid used to treat nasolabial fold wrinkles produced significantly fewer overall product-related adverse events than human-derived collagen, study results have shown.

In a randomized multicenter trial of 233 patients with nasolabial fold wrinkles, the overall product-related adverse event rate was 21% with poly-L-lactic acid (PLLA; Sculptra) and 36% with human collagen (Cosmoplast), resulting in a P value of less than .05.

Compared with the PLLA group, the collagen group had more injection-site erythema (26.5% vs. 2.6%) and pruritus (8% vs. 1%), Dr. Marta Rendon and the Cosmetic Study Trial Group reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The PLLA group reported more injection-site pain (5.2% vs. 3.4%); more application-site papules, defined as palpable elevations less than 5 mm in diameter (8.6% vs. 3.4%); and more application-site nodules, defined as lesions 5 mm or more in diameter (7% vs. 6%). The difference between the groups was statistically significant for nodules.

The papules and nodules were nonvisible, palpable, and mild or moderate in intensity; all but one event resolved spontaneously during the 13-month follow-up period.

The frequency of adverse events with injectable PLLA, including injection-site pain, papules, and nodules, was lower than reported in early published reports in patients with HIV-related facial lipoatrophy, reported Dr. Rendon, who is in private practice in Boca Raton, Fla., and her associates.

No product-related serious adverse events occurred during the study, which was sponsored by Sanofi-Aventis U.S., which markets Sculptra in the United States through its subsidiary, Dermik Laboratories.

Injectable PLLA is currently approved in the United States for HIV-related facial lipoatrophy and is under review for volume restoration and/or correction of facial wrinkles and folds.

Patients (mean age 51 years) in the study had scores of 2–4 on a 5-point photo-numeric wrinkle assessment scale (WAS) for both the right and left nasolabial fold.

They underwent bilateral injections of PLLA (maximum 5 mL of reconstituted product per session) or collagen (1–2 cc per session) at one to four treatment sessions at 3-week intervals until an optimal correction was achieved for both folds. Roughly 40% in each group were Fitzpatrick skin type III.

Both the PLLA and collagen groups had significant reductions from baseline in WAS scores 3 weeks after the last treatment, as assessed by three plastic surgeons/dermatologists blinded to treatment.

Comparisons between the two groups in the change from baseline in mean WAS scores at subsequent time points resulted in significant differences favoring PLLA at months 3, 6, 9, and 13, reported Dr. Rendon and her associates.

CHICAGO — Injectable poly-L-lactic acid used to treat nasolabial fold wrinkles produced significantly fewer overall product-related adverse events than human-derived collagen, study results have shown.

In a randomized multicenter trial of 233 patients with nasolabial fold wrinkles, the overall product-related adverse event rate was 21% with poly-L-lactic acid (PLLA; Sculptra) and 36% with human collagen (Cosmoplast), resulting in a P value of less than .05.

Compared with the PLLA group, the collagen group had more injection-site erythema (26.5% vs. 2.6%) and pruritus (8% vs. 1%), Dr. Marta Rendon and the Cosmetic Study Trial Group reported in a poster at the American Academy of Dermatology's Academy 2008 meeting.

The PLLA group reported more injection-site pain (5.2% vs. 3.4%); more application-site papules, defined as palpable elevations less than 5 mm in diameter (8.6% vs. 3.4%); and more application-site nodules, defined as lesions 5 mm or more in diameter (7% vs. 6%). The difference between the groups was statistically significant for nodules.

The papules and nodules were nonvisible, palpable, and mild or moderate in intensity; all but one event resolved spontaneously during the 13-month follow-up period.

The frequency of adverse events with injectable PLLA, including injection-site pain, papules, and nodules, was lower than reported in early published reports in patients with HIV-related facial lipoatrophy, reported Dr. Rendon, who is in private practice in Boca Raton, Fla., and her associates.

No product-related serious adverse events occurred during the study, which was sponsored by Sanofi-Aventis U.S., which markets Sculptra in the United States through its subsidiary, Dermik Laboratories.

Injectable PLLA is currently approved in the United States for HIV-related facial lipoatrophy and is under review for volume restoration and/or correction of facial wrinkles and folds.

Patients (mean age 51 years) in the study had scores of 2–4 on a 5-point photo-numeric wrinkle assessment scale (WAS) for both the right and left nasolabial fold.

They underwent bilateral injections of PLLA (maximum 5 mL of reconstituted product per session) or collagen (1–2 cc per session) at one to four treatment sessions at 3-week intervals until an optimal correction was achieved for both folds. Roughly 40% in each group were Fitzpatrick skin type III.

Both the PLLA and collagen groups had significant reductions from baseline in WAS scores 3 weeks after the last treatment, as assessed by three plastic surgeons/dermatologists blinded to treatment.

Comparisons between the two groups in the change from baseline in mean WAS scores at subsequent time points resulted in significant differences favoring PLLA at months 3, 6, 9, and 13, reported Dr. Rendon and her associates.