Christine Kilgore

Patients with hand osteoarthritis are significantly more likely to develop disease of the hip or knee later in life, a prospective, population-based study has shown.

The new findings are consistent with reports that osteoarthritis (OA) is a generalized disease in many patients, and suggest that by “identifying subjects who have a tendency for developing OA and by modifying their risk factors, it may be possible to avoid or prevent OA-related pain and disability in the weight-bearing joints,” the investigators said.

They followed 1,235 patients who had baseline radiographs of the hand, hips, and knees that showed no prevalent OA of the hip or knee (a Kellgren/Lawrence score of 0–1) and either hand OA (a Kellgren/Lawrence score of 2–4 in two of three joint groups of either hand) or no hand OA. At a mean of 6.6 years later, they obtained hip and knee radiographs again.

Independent of other known risk factors, patients with hand OA at baseline were 3 times more likely to have future hip OA and 1.6 times more likely to have future knee OA, than patients without hand OA, reported S. Dahaghin, M.D., and colleagues at the Erasmus Medical Center at the University Medical Center Rotterdam, the Netherlands (Arthritis Rheum. 2005:52;3520–7).

When they restricted their analysis to patients without any possibility of hip or knee OA at baseline (Kellgren/Lawrence score of 0, versus 0–1), they found the risk of future knee OA was the same (odds ratio 1.6) and that the risk of future hip OA was even higher (odds ratio 6.5).

Family history of OA increased the risk of future hip OA even further in patients who had hand OA at baseline. The risk of future knee OA in these patients was further increased not by family history, but when they were overweight.

Additionally, the investigators found that high baseline levels of the OA biomarker CTX-II (type II collagen C-telopeptide degradation product) increased the risk of hip and knee OA, independent of the baseline presence of hand OA or “doubtful” hip or knee OA.

Patients in the study had a mean age of 66 years. They were a randomly selected subset of participants in the Rotterdam Study, a prospective, population-based cohort study of chronic diseases in the elderly.

Patients with hand osteoarthritis are significantly more likely to develop disease of the hip or knee later in life, a prospective, population-based study has shown.

The new findings are consistent with reports that osteoarthritis (OA) is a generalized disease in many patients, and suggest that by “identifying subjects who have a tendency for developing OA and by modifying their risk factors, it may be possible to avoid or prevent OA-related pain and disability in the weight-bearing joints,” the investigators said.

They followed 1,235 patients who had baseline radiographs of the hand, hips, and knees that showed no prevalent OA of the hip or knee (a Kellgren/Lawrence score of 0–1) and either hand OA (a Kellgren/Lawrence score of 2–4 in two of three joint groups of either hand) or no hand OA. At a mean of 6.6 years later, they obtained hip and knee radiographs again.

Independent of other known risk factors, patients with hand OA at baseline were 3 times more likely to have future hip OA and 1.6 times more likely to have future knee OA, than patients without hand OA, reported S. Dahaghin, M.D., and colleagues at the Erasmus Medical Center at the University Medical Center Rotterdam, the Netherlands (Arthritis Rheum. 2005:52;3520–7).

When they restricted their analysis to patients without any possibility of hip or knee OA at baseline (Kellgren/Lawrence score of 0, versus 0–1), they found the risk of future knee OA was the same (odds ratio 1.6) and that the risk of future hip OA was even higher (odds ratio 6.5).

Family history of OA increased the risk of future hip OA even further in patients who had hand OA at baseline. The risk of future knee OA in these patients was further increased not by family history, but when they were overweight.

Additionally, the investigators found that high baseline levels of the OA biomarker CTX-II (type II collagen C-telopeptide degradation product) increased the risk of hip and knee OA, independent of the baseline presence of hand OA or “doubtful” hip or knee OA.

Patients in the study had a mean age of 66 years. They were a randomly selected subset of participants in the Rotterdam Study, a prospective, population-based cohort study of chronic diseases in the elderly.

Patients with hand osteoarthritis are significantly more likely to develop disease of the hip or knee later in life, a prospective, population-based study has shown.

The new findings are consistent with reports that osteoarthritis (OA) is a generalized disease in many patients, and suggest that by “identifying subjects who have a tendency for developing OA and by modifying their risk factors, it may be possible to avoid or prevent OA-related pain and disability in the weight-bearing joints,” the investigators said.

They followed 1,235 patients who had baseline radiographs of the hand, hips, and knees that showed no prevalent OA of the hip or knee (a Kellgren/Lawrence score of 0–1) and either hand OA (a Kellgren/Lawrence score of 2–4 in two of three joint groups of either hand) or no hand OA. At a mean of 6.6 years later, they obtained hip and knee radiographs again.

Independent of other known risk factors, patients with hand OA at baseline were 3 times more likely to have future hip OA and 1.6 times more likely to have future knee OA, than patients without hand OA, reported S. Dahaghin, M.D., and colleagues at the Erasmus Medical Center at the University Medical Center Rotterdam, the Netherlands (Arthritis Rheum. 2005:52;3520–7).

When they restricted their analysis to patients without any possibility of hip or knee OA at baseline (Kellgren/Lawrence score of 0, versus 0–1), they found the risk of future knee OA was the same (odds ratio 1.6) and that the risk of future hip OA was even higher (odds ratio 6.5).

Family history of OA increased the risk of future hip OA even further in patients who had hand OA at baseline. The risk of future knee OA in these patients was further increased not by family history, but when they were overweight.

Additionally, the investigators found that high baseline levels of the OA biomarker CTX-II (type II collagen C-telopeptide degradation product) increased the risk of hip and knee OA, independent of the baseline presence of hand OA or “doubtful” hip or knee OA.

Patients in the study had a mean age of 66 years. They were a randomly selected subset of participants in the Rotterdam Study, a prospective, population-based cohort study of chronic diseases in the elderly.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 10

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatments made with the lubricants marketed as Astroglide, FemGlide, Pre-Seed, and Replens. After 30 minutes of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants.

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

The study was conducted with all lubricants provided by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Kate Johnson of the Montreal Bureau contributed to this report.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 10

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatments made with the lubricants marketed as Astroglide, FemGlide, Pre-Seed, and Replens. After 30 minutes of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants.

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

The study was conducted with all lubricants provided by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Kate Johnson of the Montreal Bureau contributed to this report.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 10

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatments made with the lubricants marketed as Astroglide, FemGlide, Pre-Seed, and Replens. After 30 minutes of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants.

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

The study was conducted with all lubricants provided by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Kate Johnson of the Montreal Bureau contributed to this report.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Temporomandibular joint arthritis in children with juvenile idiopathic arthritis responds well to intraarticular corticosteroid injection, especially when it is administered early on, reported Bita Arabshahi, M.D., of Children's Hospital of Philadelphia, and colleagues.

Twenty-three children aged 4–16 years who had clinical evidence of temporomandibular arthritis and MRI evidence of temporomandibular joint (TMJ) inflammation underwent CT-guided steroid injection of 1 or more TMJs. Fourteen patients had follow-up MRI studies of the TMJ 6–12 months later.

Ten of 13 patients (77%) who had jaw pain before the injection had no pain after the treatment. Nearly half of all 23 patients had significant improvement in maximal incisal opening (it was below age-matched normal values in all patients), with the most significant improvements seen in patients diagnosed before 5 years of age and in those injected by age 6.

Among the 14 patients who had follow-up MRI, 13 (57%) of the 23 TMJs studied had shown acute joint effusion before injection. Corticosteroid injections resulted in resolution of effusion in more than two-thirds of the acutely affected joints, the investigators reported (Arthritis Rheum. 2005;52:3563–9).

The fact that about one-third of these patients had persistent effusion after injection suggests that “the presence or resolution of pain may not accurately predict the presence of TMJ inflammation,” said the investigators, who collected data retrospectively from medical records and prospectively from patient questionnaires.

The majority of patients were ANA-positive girls who had polyarticular juvenile idiopathic arthritis for a median of 2 years. They were treated with triamcinolone acetonide or triamcinolone hexacetonide.

Temporomandibular joint arthritis in children with juvenile idiopathic arthritis responds well to intraarticular corticosteroid injection, especially when it is administered early on, reported Bita Arabshahi, M.D., of Children's Hospital of Philadelphia, and colleagues.

Twenty-three children aged 4–16 years who had clinical evidence of temporomandibular arthritis and MRI evidence of temporomandibular joint (TMJ) inflammation underwent CT-guided steroid injection of 1 or more TMJs. Fourteen patients had follow-up MRI studies of the TMJ 6–12 months later.

Ten of 13 patients (77%) who had jaw pain before the injection had no pain after the treatment. Nearly half of all 23 patients had significant improvement in maximal incisal opening (it was below age-matched normal values in all patients), with the most significant improvements seen in patients diagnosed before 5 years of age and in those injected by age 6.

Among the 14 patients who had follow-up MRI, 13 (57%) of the 23 TMJs studied had shown acute joint effusion before injection. Corticosteroid injections resulted in resolution of effusion in more than two-thirds of the acutely affected joints, the investigators reported (Arthritis Rheum. 2005;52:3563–9).

The fact that about one-third of these patients had persistent effusion after injection suggests that “the presence or resolution of pain may not accurately predict the presence of TMJ inflammation,” said the investigators, who collected data retrospectively from medical records and prospectively from patient questionnaires.

The majority of patients were ANA-positive girls who had polyarticular juvenile idiopathic arthritis for a median of 2 years. They were treated with triamcinolone acetonide or triamcinolone hexacetonide.

Temporomandibular joint arthritis in children with juvenile idiopathic arthritis responds well to intraarticular corticosteroid injection, especially when it is administered early on, reported Bita Arabshahi, M.D., of Children's Hospital of Philadelphia, and colleagues.

Twenty-three children aged 4–16 years who had clinical evidence of temporomandibular arthritis and MRI evidence of temporomandibular joint (TMJ) inflammation underwent CT-guided steroid injection of 1 or more TMJs. Fourteen patients had follow-up MRI studies of the TMJ 6–12 months later.

Ten of 13 patients (77%) who had jaw pain before the injection had no pain after the treatment. Nearly half of all 23 patients had significant improvement in maximal incisal opening (it was below age-matched normal values in all patients), with the most significant improvements seen in patients diagnosed before 5 years of age and in those injected by age 6.

Among the 14 patients who had follow-up MRI, 13 (57%) of the 23 TMJs studied had shown acute joint effusion before injection. Corticosteroid injections resulted in resolution of effusion in more than two-thirds of the acutely affected joints, the investigators reported (Arthritis Rheum. 2005;52:3563–9).

The fact that about one-third of these patients had persistent effusion after injection suggests that “the presence or resolution of pain may not accurately predict the presence of TMJ inflammation,” said the investigators, who collected data retrospectively from medical records and prospectively from patient questionnaires.

The majority of patients were ANA-positive girls who had polyarticular juvenile idiopathic arthritis for a median of 2 years. They were treated with triamcinolone acetonide or triamcinolone hexacetonide.

GAITHERSBURG, MD. — Tamiflu appears to have played “no role” in the deaths of 12 children in Japan and in 32 reported cases of neuropsychiatric events, 31 of which also occurred in Japan, in children who received the drug after a diagnosis of influenza, the Food and Drug Administration's Pediatric Advisory Committee told the FDA and a swarm of reporters.

The panel recommended, however, that new information be added to the Tamiflu label about the possibility of serious skin reactions.

And it requested that the FDA present the committee with a “preliminary report” of findings from continued monitoring of adverse events as soon as more data are available, “even if it's only after one more flu season.”

Tamiflu, or oseltamivir, was one of eight drugs reviewed as part of a mandated 1-year postpediatric exclusivity review of adverse events.

The Best Pharmaceuticals for Children Act requires the FDA's Office of Pediatric Therapeutics to review adverse events reports received during the year after a drug is granted pediatric exclusivity, and to then refer these reports to the Pediatrics Advisory Committee for its review and recommendations.

The report on Tamiflu took on added significance because FDA officials had—independent of the exclusivity review—identified and begun investigating Japanese case reports of death and neuropsychiatric events as a result of a new monitoring system that was put in place during last year's influenza season.

News of pandemic flu preparations and reports that Tamiflu is being made available for pandemic stockpiling also fueled the interest. The FDA, in material made public before the committee meeting, said that “a better understanding of Tamiflu safety in children will be useful should a pandemic occur.”

Tamiflu was first approved in 1999 for the treatment of influenza in adults. Approval of the Tamiflu oral suspension for treatment in children aged 1 year and up followed in 2000, as did approval for prophylaxis for adults and children aged 13 and up. An application for approval for prophylaxis in children aged 1–12 years is pending.

During the period of time covered by its postexclusivity review—from March 2004 to April 2005—there were 75 adverse event reports concerning children up to 16 years of age. The majority—69 of the reports—were from Japan, 5 were from the United States, and 1 was from Canada.

Eight of the reports, all from Japan, were of deaths. Of the 67 nonfatal reports, 32 were classified as CNS reports such as hallucinations, convulsions, delirium, and abnormal behavior; 12 were deemed skin/hypersensitivity reports, and 23 covered gastrointestinal and other events.

Since the time of approval, there have been 190 reports of serious adverse events in children up to age 16 years (28 of them in the United States), and 12 of them deaths in Japan.

Some of the reported deaths involved children who died suddenly within 1–2 days of starting treatment; other deaths occurred later. Some of the children were reported to be previously healthy, and others had asthma or other medical problems. Brain and pulmonary edema were reported in some cases, encephalopathy in others. One report says that a 14-year-old boy “took his own life” after taking Tamiflu, said Melissa Truffa, a registered pharmacist with the FDA's division of drug risk evaluation in Rockville, Md.

In general, many of the cases involve comorbidities and confounding factors, and the majority have limited or missing data. Combined with the fact that neurologic complications are not uncommon during influenza viral infections, “it's difficult to establish a direct casual relationship between the use of oseltamivir and the reported deaths,” Ms. Truffa told the committee.

Influenza-associated encephalopathy and neuropsychiatric events have been a concern in Japan for over a decade, and national surveillance is strong. The Japanese national health service also facilitates rapid diagnosis and early treatment of influenza, said Linda Lewis, M.D., of the FDA's division of antiviral products in Rockville.

This, said panel member Janet Englund, M.D., stands in stark contrast to the United States. “We are not good at diagnosing influenza. … We absolutely underdiagnose it,” said Dr. Englund, of Children's Hospital and Regional Medical Center in Seattle. “And I know that in our region, there have been shortages [of Tamiflu]. … It's just not used that much.”

According to the drug's manufacturer, Hoffman-La Roche, since 2001 there have been 24.5 million prescriptions in Japan, 11.6 million of them for children. In the United States, there have been 6.5 million prescriptions—approximately 872,000 of them for children.

According to Ms. Truffa, while the overall number of Tamiflu prescriptions has risen in the United States in the past 2 years, the percentage of total prescriptions that are written for children has declined from 40% 3 years ago to 25% last year.

The reports of death and neuropsychiatric adverse events from Japan most likely reflect greater use of the drug and more reporting of influenza-associated adverse events; they may partly reflect unknown pathophysiologic differences, Dr. Lewis said. Dosing, she noted, is similar in the United States and Japan.

It is possible, she said, “that similar events might be reported in the United States if Tamiflu use increases substantially or, especially, if awareness of neuropsychiatric complications [of influenza] increases.”

Of the 12 reports of skin hypersensitivity reactions that were filed during Tamiflu's postexclusivity period, four cases were “notable cases” that “could have possibly been caused by Tamiflu,” Ms. Truffa told the committee.

These and other cases identified from a review of adverse events from the 2004–2005 flu season prompted the FDA to further investigate all reports of serious skin and hypersensitivity reactions. Officials found 16 reports of serious skin reactions, 18 reports of anaphylaxis, and 1 associated death in children from the time of Tamiflu's approval to April 2005.

Additional data are currently under review, and the FDA will propose additional information in the Tamiflu labeling regarding serious skin reactions, FDA officials told the committee.

Current labeling lists dermatitis, rash, swelling of the face or tongue, and toxic epidermal necrolysis as observed and adverse reactions of the drug.

A reanalysis of data from the pediatric clinical trials of Tamiflu, as well as a literature review, failed to identify any differences in both skin and neuropsychiatric adverse events between children with influenza who received Tamiflu and those who received placebo or no treatment, Dr. Lewis said.

FDA Panel Clears Two Other Drugs

Sumatriptan and fluconazole were among the drugs that received a green light for routine adverse event monitoring by the Food and Drug Administration's Pediatric Advisory Committee.

The committee gave the thumbs-up after the FDA reported that there were no new unlabeled safety concerns identified in the pediatric adverse events that were reported during the drugs' 1-year postexclusivity periods.

There were six unduplicated pediatric adverse events reports associated with the sumatriptan (Imitrex) nasal spray for treatment of migraine, and none of the reports were serious or life threatening, reported Susan McCune, M.D., a medical officer in the FDA's division of pediatric drug development, Rockville, Md.

For the antifungal fluconazole (Diflucan), there were 19 unduplicated reports of adverse events in children, including four deaths. Most reports were “highly confounded” by underlying illness and concomitant medications, and “although serious adverse events occurred, most were expected or addressed in the drug's labeling,” said Larry Grylack, M.D., also of the FDA's division of pediatric drug development.

The 15 nonfatal adverse events reported in patients taking Diflucan involved the following: congenital anomalies in three reports, cardiac events in three, metabolic problems in two, hepatic problems in two, nonfatal fungemia in two, dosing errors in two, and hypersensitivity in one.

Dr. Grylack also reported that there were no new safety concerns identified for the NSAID rofecoxib (Vioxx). During a 7-month exclusivity period, there were 19 pediatric reports, including three foreign deaths, associated with the drug. No further monitoring is necessary, he said, since the drug has been withdrawn from the market.

The other drugs reviewed that also had no new safety concerns were antineoplastic agent irinotecan (Camptosar), antineoplastic agent carboplatin (Paraplatin), platelet-reducing agent anagrelide (Agrylin), and hematinic agent sodium ferric gluconate complex (Ferrlecit).

GAITHERSBURG, MD. — Tamiflu appears to have played “no role” in the deaths of 12 children in Japan and in 32 reported cases of neuropsychiatric events, 31 of which also occurred in Japan, in children who received the drug after a diagnosis of influenza, the Food and Drug Administration's Pediatric Advisory Committee told the FDA and a swarm of reporters.

The panel recommended, however, that new information be added to the Tamiflu label about the possibility of serious skin reactions.

And it requested that the FDA present the committee with a “preliminary report” of findings from continued monitoring of adverse events as soon as more data are available, “even if it's only after one more flu season.”

Tamiflu, or oseltamivir, was one of eight drugs reviewed as part of a mandated 1-year postpediatric exclusivity review of adverse events.

The Best Pharmaceuticals for Children Act requires the FDA's Office of Pediatric Therapeutics to review adverse events reports received during the year after a drug is granted pediatric exclusivity, and to then refer these reports to the Pediatrics Advisory Committee for its review and recommendations.

The report on Tamiflu took on added significance because FDA officials had—independent of the exclusivity review—identified and begun investigating Japanese case reports of death and neuropsychiatric events as a result of a new monitoring system that was put in place during last year's influenza season.

News of pandemic flu preparations and reports that Tamiflu is being made available for pandemic stockpiling also fueled the interest. The FDA, in material made public before the committee meeting, said that “a better understanding of Tamiflu safety in children will be useful should a pandemic occur.”

Tamiflu was first approved in 1999 for the treatment of influenza in adults. Approval of the Tamiflu oral suspension for treatment in children aged 1 year and up followed in 2000, as did approval for prophylaxis for adults and children aged 13 and up. An application for approval for prophylaxis in children aged 1–12 years is pending.

During the period of time covered by its postexclusivity review—from March 2004 to April 2005—there were 75 adverse event reports concerning children up to 16 years of age. The majority—69 of the reports—were from Japan, 5 were from the United States, and 1 was from Canada.

Eight of the reports, all from Japan, were of deaths. Of the 67 nonfatal reports, 32 were classified as CNS reports such as hallucinations, convulsions, delirium, and abnormal behavior; 12 were deemed skin/hypersensitivity reports, and 23 covered gastrointestinal and other events.

Since the time of approval, there have been 190 reports of serious adverse events in children up to age 16 years (28 of them in the United States), and 12 of them deaths in Japan.

Some of the reported deaths involved children who died suddenly within 1–2 days of starting treatment; other deaths occurred later. Some of the children were reported to be previously healthy, and others had asthma or other medical problems. Brain and pulmonary edema were reported in some cases, encephalopathy in others. One report says that a 14-year-old boy “took his own life” after taking Tamiflu, said Melissa Truffa, a registered pharmacist with the FDA's division of drug risk evaluation in Rockville, Md.

In general, many of the cases involve comorbidities and confounding factors, and the majority have limited or missing data. Combined with the fact that neurologic complications are not uncommon during influenza viral infections, “it's difficult to establish a direct casual relationship between the use of oseltamivir and the reported deaths,” Ms. Truffa told the committee.

Influenza-associated encephalopathy and neuropsychiatric events have been a concern in Japan for over a decade, and national surveillance is strong. The Japanese national health service also facilitates rapid diagnosis and early treatment of influenza, said Linda Lewis, M.D., of the FDA's division of antiviral products in Rockville.

This, said panel member Janet Englund, M.D., stands in stark contrast to the United States. “We are not good at diagnosing influenza. … We absolutely underdiagnose it,” said Dr. Englund, of Children's Hospital and Regional Medical Center in Seattle. “And I know that in our region, there have been shortages [of Tamiflu]. … It's just not used that much.”

According to the drug's manufacturer, Hoffman-La Roche, since 2001 there have been 24.5 million prescriptions in Japan, 11.6 million of them for children. In the United States, there have been 6.5 million prescriptions—approximately 872,000 of them for children.

According to Ms. Truffa, while the overall number of Tamiflu prescriptions has risen in the United States in the past 2 years, the percentage of total prescriptions that are written for children has declined from 40% 3 years ago to 25% last year.

The reports of death and neuropsychiatric adverse events from Japan most likely reflect greater use of the drug and more reporting of influenza-associated adverse events; they may partly reflect unknown pathophysiologic differences, Dr. Lewis said. Dosing, she noted, is similar in the United States and Japan.

It is possible, she said, “that similar events might be reported in the United States if Tamiflu use increases substantially or, especially, if awareness of neuropsychiatric complications [of influenza] increases.”

Of the 12 reports of skin hypersensitivity reactions that were filed during Tamiflu's postexclusivity period, four cases were “notable cases” that “could have possibly been caused by Tamiflu,” Ms. Truffa told the committee.

These and other cases identified from a review of adverse events from the 2004–2005 flu season prompted the FDA to further investigate all reports of serious skin and hypersensitivity reactions. Officials found 16 reports of serious skin reactions, 18 reports of anaphylaxis, and 1 associated death in children from the time of Tamiflu's approval to April 2005.

Additional data are currently under review, and the FDA will propose additional information in the Tamiflu labeling regarding serious skin reactions, FDA officials told the committee.

Current labeling lists dermatitis, rash, swelling of the face or tongue, and toxic epidermal necrolysis as observed and adverse reactions of the drug.

A reanalysis of data from the pediatric clinical trials of Tamiflu, as well as a literature review, failed to identify any differences in both skin and neuropsychiatric adverse events between children with influenza who received Tamiflu and those who received placebo or no treatment, Dr. Lewis said.

FDA Panel Clears Two Other Drugs

Sumatriptan and fluconazole were among the drugs that received a green light for routine adverse event monitoring by the Food and Drug Administration's Pediatric Advisory Committee.

The committee gave the thumbs-up after the FDA reported that there were no new unlabeled safety concerns identified in the pediatric adverse events that were reported during the drugs' 1-year postexclusivity periods.

There were six unduplicated pediatric adverse events reports associated with the sumatriptan (Imitrex) nasal spray for treatment of migraine, and none of the reports were serious or life threatening, reported Susan McCune, M.D., a medical officer in the FDA's division of pediatric drug development, Rockville, Md.

For the antifungal fluconazole (Diflucan), there were 19 unduplicated reports of adverse events in children, including four deaths. Most reports were “highly confounded” by underlying illness and concomitant medications, and “although serious adverse events occurred, most were expected or addressed in the drug's labeling,” said Larry Grylack, M.D., also of the FDA's division of pediatric drug development.

The 15 nonfatal adverse events reported in patients taking Diflucan involved the following: congenital anomalies in three reports, cardiac events in three, metabolic problems in two, hepatic problems in two, nonfatal fungemia in two, dosing errors in two, and hypersensitivity in one.

Dr. Grylack also reported that there were no new safety concerns identified for the NSAID rofecoxib (Vioxx). During a 7-month exclusivity period, there were 19 pediatric reports, including three foreign deaths, associated with the drug. No further monitoring is necessary, he said, since the drug has been withdrawn from the market.

The other drugs reviewed that also had no new safety concerns were antineoplastic agent irinotecan (Camptosar), antineoplastic agent carboplatin (Paraplatin), platelet-reducing agent anagrelide (Agrylin), and hematinic agent sodium ferric gluconate complex (Ferrlecit).

GAITHERSBURG, MD. — Tamiflu appears to have played “no role” in the deaths of 12 children in Japan and in 32 reported cases of neuropsychiatric events, 31 of which also occurred in Japan, in children who received the drug after a diagnosis of influenza, the Food and Drug Administration's Pediatric Advisory Committee told the FDA and a swarm of reporters.

The panel recommended, however, that new information be added to the Tamiflu label about the possibility of serious skin reactions.

And it requested that the FDA present the committee with a “preliminary report” of findings from continued monitoring of adverse events as soon as more data are available, “even if it's only after one more flu season.”

Tamiflu, or oseltamivir, was one of eight drugs reviewed as part of a mandated 1-year postpediatric exclusivity review of adverse events.

The Best Pharmaceuticals for Children Act requires the FDA's Office of Pediatric Therapeutics to review adverse events reports received during the year after a drug is granted pediatric exclusivity, and to then refer these reports to the Pediatrics Advisory Committee for its review and recommendations.

The report on Tamiflu took on added significance because FDA officials had—independent of the exclusivity review—identified and begun investigating Japanese case reports of death and neuropsychiatric events as a result of a new monitoring system that was put in place during last year's influenza season.

News of pandemic flu preparations and reports that Tamiflu is being made available for pandemic stockpiling also fueled the interest. The FDA, in material made public before the committee meeting, said that “a better understanding of Tamiflu safety in children will be useful should a pandemic occur.”

Tamiflu was first approved in 1999 for the treatment of influenza in adults. Approval of the Tamiflu oral suspension for treatment in children aged 1 year and up followed in 2000, as did approval for prophylaxis for adults and children aged 13 and up. An application for approval for prophylaxis in children aged 1–12 years is pending.

During the period of time covered by its postexclusivity review—from March 2004 to April 2005—there were 75 adverse event reports concerning children up to 16 years of age. The majority—69 of the reports—were from Japan, 5 were from the United States, and 1 was from Canada.

Eight of the reports, all from Japan, were of deaths. Of the 67 nonfatal reports, 32 were classified as CNS reports such as hallucinations, convulsions, delirium, and abnormal behavior; 12 were deemed skin/hypersensitivity reports, and 23 covered gastrointestinal and other events.

Since the time of approval, there have been 190 reports of serious adverse events in children up to age 16 years (28 of them in the United States), and 12 of them deaths in Japan.

Some of the reported deaths involved children who died suddenly within 1–2 days of starting treatment; other deaths occurred later. Some of the children were reported to be previously healthy, and others had asthma or other medical problems. Brain and pulmonary edema were reported in some cases, encephalopathy in others. One report says that a 14-year-old boy “took his own life” after taking Tamiflu, said Melissa Truffa, a registered pharmacist with the FDA's division of drug risk evaluation in Rockville, Md.

In general, many of the cases involve comorbidities and confounding factors, and the majority have limited or missing data. Combined with the fact that neurologic complications are not uncommon during influenza viral infections, “it's difficult to establish a direct casual relationship between the use of oseltamivir and the reported deaths,” Ms. Truffa told the committee.

Influenza-associated encephalopathy and neuropsychiatric events have been a concern in Japan for over a decade, and national surveillance is strong. The Japanese national health service also facilitates rapid diagnosis and early treatment of influenza, said Linda Lewis, M.D., of the FDA's division of antiviral products in Rockville.

This, said panel member Janet Englund, M.D., stands in stark contrast to the United States. “We are not good at diagnosing influenza. … We absolutely underdiagnose it,” said Dr. Englund, of Children's Hospital and Regional Medical Center in Seattle. “And I know that in our region, there have been shortages [of Tamiflu]. … It's just not used that much.”

According to the drug's manufacturer, Hoffman-La Roche, since 2001 there have been 24.5 million prescriptions in Japan, 11.6 million of them for children. In the United States, there have been 6.5 million prescriptions—approximately 872,000 of them for children.

According to Ms. Truffa, while the overall number of Tamiflu prescriptions has risen in the United States in the past 2 years, the percentage of total prescriptions that are written for children has declined from 40% 3 years ago to 25% last year.

The reports of death and neuropsychiatric adverse events from Japan most likely reflect greater use of the drug and more reporting of influenza-associated adverse events; they may partly reflect unknown pathophysiologic differences, Dr. Lewis said. Dosing, she noted, is similar in the United States and Japan.

It is possible, she said, “that similar events might be reported in the United States if Tamiflu use increases substantially or, especially, if awareness of neuropsychiatric complications [of influenza] increases.”

Of the 12 reports of skin hypersensitivity reactions that were filed during Tamiflu's postexclusivity period, four cases were “notable cases” that “could have possibly been caused by Tamiflu,” Ms. Truffa told the committee.

These and other cases identified from a review of adverse events from the 2004–2005 flu season prompted the FDA to further investigate all reports of serious skin and hypersensitivity reactions. Officials found 16 reports of serious skin reactions, 18 reports of anaphylaxis, and 1 associated death in children from the time of Tamiflu's approval to April 2005.

Additional data are currently under review, and the FDA will propose additional information in the Tamiflu labeling regarding serious skin reactions, FDA officials told the committee.

Current labeling lists dermatitis, rash, swelling of the face or tongue, and toxic epidermal necrolysis as observed and adverse reactions of the drug.

A reanalysis of data from the pediatric clinical trials of Tamiflu, as well as a literature review, failed to identify any differences in both skin and neuropsychiatric adverse events between children with influenza who received Tamiflu and those who received placebo or no treatment, Dr. Lewis said.

FDA Panel Clears Two Other Drugs

Sumatriptan and fluconazole were among the drugs that received a green light for routine adverse event monitoring by the Food and Drug Administration's Pediatric Advisory Committee.

The committee gave the thumbs-up after the FDA reported that there were no new unlabeled safety concerns identified in the pediatric adverse events that were reported during the drugs' 1-year postexclusivity periods.

There were six unduplicated pediatric adverse events reports associated with the sumatriptan (Imitrex) nasal spray for treatment of migraine, and none of the reports were serious or life threatening, reported Susan McCune, M.D., a medical officer in the FDA's division of pediatric drug development, Rockville, Md.

For the antifungal fluconazole (Diflucan), there were 19 unduplicated reports of adverse events in children, including four deaths. Most reports were “highly confounded” by underlying illness and concomitant medications, and “although serious adverse events occurred, most were expected or addressed in the drug's labeling,” said Larry Grylack, M.D., also of the FDA's division of pediatric drug development.

The 15 nonfatal adverse events reported in patients taking Diflucan involved the following: congenital anomalies in three reports, cardiac events in three, metabolic problems in two, hepatic problems in two, nonfatal fungemia in two, dosing errors in two, and hypersensitivity in one.

Dr. Grylack also reported that there were no new safety concerns identified for the NSAID rofecoxib (Vioxx). During a 7-month exclusivity period, there were 19 pediatric reports, including three foreign deaths, associated with the drug. No further monitoring is necessary, he said, since the drug has been withdrawn from the market.

The other drugs reviewed that also had no new safety concerns were antineoplastic agent irinotecan (Camptosar), antineoplastic agent carboplatin (Paraplatin), platelet-reducing agent anagrelide (Agrylin), and hematinic agent sodium ferric gluconate complex (Ferrlecit).

WASHINGTON — Screening for parental depression at well-child visits is feasible and parents are receptive to the idea, Ardis L. Olson, M.D., reported at the annual meeting of the Pediatric Academic Societies.

A brief, validated questionnaire, the two-question version of the Patient Health Questionnaire depression module (PHQ-2), was completed by almost 8,000 parents in about half of the well-child visits conducted in six small- to medium-sized practices during a 6-month period.

The practices had been prepared for screening with provider and parent education, said Dr. Olson of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Rates of positive PHQ-2 screens were similar for both mothers and fathers (about 5% for each). Pediatricians were more likely to refer mothers who screened positively (39%) than fathers who screened positively (21%), however, to primary care or mental health providers. They were equally as likely to refer mothers and fathers (26%) to a telephone support referral service called the Parent Support Line.

One-quarter of the parents accepted the services of the Parent Support Line when they were offered a call from the service, while fewer than 1% accessed the service when given a Web site or 800 number—a finding that indicates that follow-up must be proactive, Dr. Olson said.

WASHINGTON — Screening for parental depression at well-child visits is feasible and parents are receptive to the idea, Ardis L. Olson, M.D., reported at the annual meeting of the Pediatric Academic Societies.

A brief, validated questionnaire, the two-question version of the Patient Health Questionnaire depression module (PHQ-2), was completed by almost 8,000 parents in about half of the well-child visits conducted in six small- to medium-sized practices during a 6-month period.

The practices had been prepared for screening with provider and parent education, said Dr. Olson of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Rates of positive PHQ-2 screens were similar for both mothers and fathers (about 5% for each). Pediatricians were more likely to refer mothers who screened positively (39%) than fathers who screened positively (21%), however, to primary care or mental health providers. They were equally as likely to refer mothers and fathers (26%) to a telephone support referral service called the Parent Support Line.

One-quarter of the parents accepted the services of the Parent Support Line when they were offered a call from the service, while fewer than 1% accessed the service when given a Web site or 800 number—a finding that indicates that follow-up must be proactive, Dr. Olson said.

WASHINGTON — Screening for parental depression at well-child visits is feasible and parents are receptive to the idea, Ardis L. Olson, M.D., reported at the annual meeting of the Pediatric Academic Societies.

A brief, validated questionnaire, the two-question version of the Patient Health Questionnaire depression module (PHQ-2), was completed by almost 8,000 parents in about half of the well-child visits conducted in six small- to medium-sized practices during a 6-month period.

The practices had been prepared for screening with provider and parent education, said Dr. Olson of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Rates of positive PHQ-2 screens were similar for both mothers and fathers (about 5% for each). Pediatricians were more likely to refer mothers who screened positively (39%) than fathers who screened positively (21%), however, to primary care or mental health providers. They were equally as likely to refer mothers and fathers (26%) to a telephone support referral service called the Parent Support Line.

One-quarter of the parents accepted the services of the Parent Support Line when they were offered a call from the service, while fewer than 1% accessed the service when given a Web site or 800 number—a finding that indicates that follow-up must be proactive, Dr. Olson said.

CT scanning without oral contrast worked as well or better for diagnosing appendicitis as CT scanning with oral contrast, investigators of a systematic review have reported.

If results of the new review are confirmed through prospective comparative trials, physicians may be able to save hours of time—as well as money and patient dissatisfaction—by foregoing use of the contrast agents and using the less burdensome noncontrast CT more commonly, according to Brock A. Anderson, M.D., and his colleagues at the University of Washington, Seattle.

That could help lower the stagnant rate of negative appendectomy, which stands at 15% of the more than 250,000 appendectomies performed each year, and up to 25% in women of reproductive age.

Imaging using oral contrast is the most prevalent method, but it's often poorly tolerated, delays treatment, and may be responsible for the possible underuse of scans in patients with suspected appendicitis, the investigators said. Rectal contrast is sometimes used, but is uncomfortable and does not always reach the cecum, they added.

The investigators identified 23 studies, most of them prospective, involving almost 3,500 adults who underwent CT scanning for suspected appendicitis with one of five protocols: CT with rectal contrast, oral contrast, rectal and oral contrast, oral and intravenous contrast, and no contrast (Am. J. Surg. 2005;190:474–8).

When they aggregated data for each of the five protocols, the researchers found that specificity, negative predictive value, and accuracy were similar among all scanning modes (specificity ranged from 95% to 98%, negative predictive value from 94% to 99%, and accuracy from 92% to 97%). Sensitivity (83%–97%) and positive predictive value (86%–98%) varied more.

Surprisingly, when the investigators aggregated data into just two groups—CT scans with oral contrast and those without oral contrast (noncontrast and rectal contrast)—they found that CT without oral contrast had greater specificity (97% vs. 94%), greater positive predictive value (97% vs. 89%), and better accuracy (96% vs. 92%) than CT with oral contrast.

Scans omitting oral contrast also had similar sensitivity (95% vs. 92%) and the same negative predictive value (96%) when compared with CT scanning with oral contrast, the investigators said.

“The finding that unenhanced CT had superior diagnostic accuracy, compared with scans performed with oral contrast, confounds conventional wisdom,” the investigators said.

They suspect that selection bias—the possibility, for instance, that centers reporting noncontrast CT results may already be “expert” scan interpreters from years of experience with contrast—may be involved. So could patient selection issues: 70% of reports detailing results of CT with oral contrast included patients with atypical presentation, compared with only 42% of those reporting noncontrast CT.

Still, the findings “suggest that broader use of CT without oral contrast may be a useful approach to overcome one barrier to the use of diagnostic imaging in patients with suspected appendicitis,” they said.

In the meantime, centers should periodically review the accuracy of noncontrast CT scans and “determine center-specific results,” advised the investigators.

Scans done without oral or IV contrast, they caution, can be tricky to interpret in thinner patients, in whom the lack of significant retroperitoneal fat can make identification of the appendix and surrounding inflammation difficult.

Without contrast, it is also easier to miss other pathology that may help explain a patient's pain, the investigators noted.

Scans in all reviewed studies were confirmed by pathologic findings or by clinical follow-up evaluation.

CT scanning without oral contrast worked as well or better for diagnosing appendicitis as CT scanning with oral contrast, investigators of a systematic review have reported.

If results of the new review are confirmed through prospective comparative trials, physicians may be able to save hours of time—as well as money and patient dissatisfaction—by foregoing use of the contrast agents and using the less burdensome noncontrast CT more commonly, according to Brock A. Anderson, M.D., and his colleagues at the University of Washington, Seattle.

That could help lower the stagnant rate of negative appendectomy, which stands at 15% of the more than 250,000 appendectomies performed each year, and up to 25% in women of reproductive age.

Imaging using oral contrast is the most prevalent method, but it's often poorly tolerated, delays treatment, and may be responsible for the possible underuse of scans in patients with suspected appendicitis, the investigators said. Rectal contrast is sometimes used, but is uncomfortable and does not always reach the cecum, they added.

The investigators identified 23 studies, most of them prospective, involving almost 3,500 adults who underwent CT scanning for suspected appendicitis with one of five protocols: CT with rectal contrast, oral contrast, rectal and oral contrast, oral and intravenous contrast, and no contrast (Am. J. Surg. 2005;190:474–8).

When they aggregated data for each of the five protocols, the researchers found that specificity, negative predictive value, and accuracy were similar among all scanning modes (specificity ranged from 95% to 98%, negative predictive value from 94% to 99%, and accuracy from 92% to 97%). Sensitivity (83%–97%) and positive predictive value (86%–98%) varied more.

Surprisingly, when the investigators aggregated data into just two groups—CT scans with oral contrast and those without oral contrast (noncontrast and rectal contrast)—they found that CT without oral contrast had greater specificity (97% vs. 94%), greater positive predictive value (97% vs. 89%), and better accuracy (96% vs. 92%) than CT with oral contrast.

Scans omitting oral contrast also had similar sensitivity (95% vs. 92%) and the same negative predictive value (96%) when compared with CT scanning with oral contrast, the investigators said.

“The finding that unenhanced CT had superior diagnostic accuracy, compared with scans performed with oral contrast, confounds conventional wisdom,” the investigators said.

They suspect that selection bias—the possibility, for instance, that centers reporting noncontrast CT results may already be “expert” scan interpreters from years of experience with contrast—may be involved. So could patient selection issues: 70% of reports detailing results of CT with oral contrast included patients with atypical presentation, compared with only 42% of those reporting noncontrast CT.

Still, the findings “suggest that broader use of CT without oral contrast may be a useful approach to overcome one barrier to the use of diagnostic imaging in patients with suspected appendicitis,” they said.

In the meantime, centers should periodically review the accuracy of noncontrast CT scans and “determine center-specific results,” advised the investigators.

Scans done without oral or IV contrast, they caution, can be tricky to interpret in thinner patients, in whom the lack of significant retroperitoneal fat can make identification of the appendix and surrounding inflammation difficult.

Without contrast, it is also easier to miss other pathology that may help explain a patient's pain, the investigators noted.

Scans in all reviewed studies were confirmed by pathologic findings or by clinical follow-up evaluation.

CT scanning without oral contrast worked as well or better for diagnosing appendicitis as CT scanning with oral contrast, investigators of a systematic review have reported.

If results of the new review are confirmed through prospective comparative trials, physicians may be able to save hours of time—as well as money and patient dissatisfaction—by foregoing use of the contrast agents and using the less burdensome noncontrast CT more commonly, according to Brock A. Anderson, M.D., and his colleagues at the University of Washington, Seattle.

That could help lower the stagnant rate of negative appendectomy, which stands at 15% of the more than 250,000 appendectomies performed each year, and up to 25% in women of reproductive age.

Imaging using oral contrast is the most prevalent method, but it's often poorly tolerated, delays treatment, and may be responsible for the possible underuse of scans in patients with suspected appendicitis, the investigators said. Rectal contrast is sometimes used, but is uncomfortable and does not always reach the cecum, they added.

The investigators identified 23 studies, most of them prospective, involving almost 3,500 adults who underwent CT scanning for suspected appendicitis with one of five protocols: CT with rectal contrast, oral contrast, rectal and oral contrast, oral and intravenous contrast, and no contrast (Am. J. Surg. 2005;190:474–8).

When they aggregated data for each of the five protocols, the researchers found that specificity, negative predictive value, and accuracy were similar among all scanning modes (specificity ranged from 95% to 98%, negative predictive value from 94% to 99%, and accuracy from 92% to 97%). Sensitivity (83%–97%) and positive predictive value (86%–98%) varied more.

Surprisingly, when the investigators aggregated data into just two groups—CT scans with oral contrast and those without oral contrast (noncontrast and rectal contrast)—they found that CT without oral contrast had greater specificity (97% vs. 94%), greater positive predictive value (97% vs. 89%), and better accuracy (96% vs. 92%) than CT with oral contrast.

Scans omitting oral contrast also had similar sensitivity (95% vs. 92%) and the same negative predictive value (96%) when compared with CT scanning with oral contrast, the investigators said.

“The finding that unenhanced CT had superior diagnostic accuracy, compared with scans performed with oral contrast, confounds conventional wisdom,” the investigators said.

They suspect that selection bias—the possibility, for instance, that centers reporting noncontrast CT results may already be “expert” scan interpreters from years of experience with contrast—may be involved. So could patient selection issues: 70% of reports detailing results of CT with oral contrast included patients with atypical presentation, compared with only 42% of those reporting noncontrast CT.

Still, the findings “suggest that broader use of CT without oral contrast may be a useful approach to overcome one barrier to the use of diagnostic imaging in patients with suspected appendicitis,” they said.

In the meantime, centers should periodically review the accuracy of noncontrast CT scans and “determine center-specific results,” advised the investigators.

Scans done without oral or IV contrast, they caution, can be tricky to interpret in thinner patients, in whom the lack of significant retroperitoneal fat can make identification of the appendix and surrounding inflammation difficult.

Without contrast, it is also easier to miss other pathology that may help explain a patient's pain, the investigators noted.

Scans in all reviewed studies were confirmed by pathologic findings or by clinical follow-up evaluation.

Kate Johnson of the Montreal Bureau contributed to this report.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“Despite warnings by researchers, there is still great confusion among physicians and subfertile couples who are trying to conceive. These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 106/mL using HTF with 10% human serum albumin.

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatm es of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants. After culture, the spermatozoa were flash frozen and analyzed for the percent damaged chromatin using the percent DNA fragmentation index (DFI).

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

“Sperm motility changes occur in a rather quick fashion, and DNA damage takes a little more time,” Dr. Agarwal told this newspaper. “We thought 4 hours [to evaluate DNA damage] is reflective of the real physiologic process.”

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

At this time, “physicians should just be aware that not every jelly and lubricant is equal. The idea that almost all lubricants not containing spermicides will not damage the sperm is a common misperception,” Dr. Agarwal said.

In fact, the loss of motility observed with three of the four lubricants studied “is similar [in magnitude] to the loss of motility found with contraceptive gels,” he said.

The study was conducted with all lubricants provided at no cost by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Kate Johnson of the Montreal Bureau contributed to this report.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“Despite warnings by researchers, there is still great confusion among physicians and subfertile couples who are trying to conceive. These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 106/mL using HTF with 10% human serum albumin.

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatm es of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants. After culture, the spermatozoa were flash frozen and analyzed for the percent damaged chromatin using the percent DNA fragmentation index (DFI).

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

“Sperm motility changes occur in a rather quick fashion, and DNA damage takes a little more time,” Dr. Agarwal told this newspaper. “We thought 4 hours [to evaluate DNA damage] is reflective of the real physiologic process.”

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

At this time, “physicians should just be aware that not every jelly and lubricant is equal. The idea that almost all lubricants not containing spermicides will not damage the sperm is a common misperception,” Dr. Agarwal said.

In fact, the loss of motility observed with three of the four lubricants studied “is similar [in magnitude] to the loss of motility found with contraceptive gels,” he said.

The study was conducted with all lubricants provided at no cost by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Kate Johnson of the Montreal Bureau contributed to this report.

MONTREAL — Three out of four commonly used vaginal lubricants caused significant decreases in sperm motility in a prospective, controlled study—and it appears that these and other lubricants can impact chromatin integrity as well, Ashok Agarwal, Ph.D., reported.

“Despite warnings by researchers, there is still great confusion among physicians and subfertile couples who are trying to conceive. These lubricants may impact the fertilization process and cause a failure of fertilization,” he said at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Of the approximately 11 million couples in the United States who are trying to conceive—6 million of whom have been trying for more than 1 year—an estimated 75% experience an increased incidence of vaginal dryness, Dr. Agarwal told this newspaper, referring in part to data from the National Center for Health Statistics and the Centers for Disease Control and Prevention.

The researchers collected sperm either incubated at 37° C in human tubal fluid (HTF) media (the controls) or in 10% lubricant treatments made with the lubricant samples from normal donors and diluted these samples to 20–40 × 106/mL using HTF with 10% human serum albumin.

In one part of the study, sperm samples from 13 donors were either incubated at 37° C in HTF (the controls) or in 10% lubricant treatm es of culture, the mean percentage of progressively motile sperm differed significantly between the controls and three of the four lubricant groups.

Sperm exposed to FemGlide, for instance, were 22% less motile than sperm incubated in HTF.

There were even greater decreases in motility—an 89% decrease and a 60% decrease—in sperm exposed to Replens and Astroglide, respectively, compared with sperm in the control group, reported Dr. Agarwal, director of the Clinical Andrology Laboratory and Reproductive Research Center at the Cleveland Clinic.

In the second part of the study, sperm from 12 donors were processed in the same way and placed in either HTF or 10% KY Jelly, FemGlide, or Pre-Seed. The sperm were cultured for 4 hours to evaluate sperm chromatic integrity after longer exposure to lubricants. After culture, the spermatozoa were flash frozen and analyzed for the percent damaged chromatin using the percent DNA fragmentation index (DFI).

There was no significant difference in the percent damaged chromatin between the HTF control group and the Pre-Seed group. There was a 15% and a 10% increase in DFI after exposure to FemGlide and KY, respectively, compared with control.

“Sperm motility changes occur in a rather quick fashion, and DNA damage takes a little more time,” Dr. Agarwal told this newspaper. “We thought 4 hours [to evaluate DNA damage] is reflective of the real physiologic process.”

Because the lubricant Pre-Seed caused little difference in either sperm motility or chromatin integrity, compared with controls, “we can say that, from our study, this particular compound does appear to fare much better,” he said. “But there should be more studies done in other centers that involve larger numbers of patients.”

At this time, “physicians should just be aware that not every jelly and lubricant is equal. The idea that almost all lubricants not containing spermicides will not damage the sperm is a common misperception,” Dr. Agarwal said.

In fact, the loss of motility observed with three of the four lubricants studied “is similar [in magnitude] to the loss of motility found with contraceptive gels,” he said.

The study was conducted with all lubricants provided at no cost by INGfertility Inc., the manufacturer of Pre-Seed, Dr. Agarwal said. He reported no conflicts of interest.

Use of concomitant folic acid significantly reduced the efficacy of methotrexate and did not decrease the overall incidence of symptomatic adverse events, according to the findings of a post hoc analysis.

The two phase III, randomized, controlled trials included in the analysis—one conducted in the United States and the other in Europe—compared the effects of 52 weeks of daily leflunomide with weekly methotrexate (MTX) in patients with active rheumatoid arthritis.

Although measuring the effect of folic acid was not the primary objective, the trials provided a look at its effect, because almost all of the patients in the MTX arm of the U.S. study—98%—were given daily folic acid, yet only 10% of the patients receiving MTX in the multinational European study received folate, each of them after they experienced an adverse event.

Previously published articles on the trials reported that 52% of patients in the MTX arm of the U.S. study achieved an American College of Rheumatology (ACR) 20 improvement response, compared with 65% of patients in the European trial.

Investigators of the new post hoc analysis set out to adjust for significant differences in the baseline characteristics of patients that made comparisons at 52 weeks “difficult to interpret,” explained Dinesh Khanna, M.D., of the University of Cincinnati and the Veterans Affairs Medical Center.

Using propensity score matching methods to adjust for these baseline differences, they found that folic acid use reduced the probability of an ACR 20 response by 15%–21%, or an average of 17%, in 225 patients who received the treatment compared with 443 patients who did not (Arthritis Rheum. 2005: 52;3030–38).

The results were consistent when comparing ACR 50 and ACR 70 improvement responses, the investigators said.

When they stratified patients by the presence or absence of rheumatoid factor, they found a statistical trend toward a lower ACR 20 response rate in the RF-negative group taking folic acid compared with the RF-positive group taking folic acid—a finding that “may suggest a preferential response to MTX in patients with active RA based on their RF status,” they said.

Adverse events were reported in 93% of patients in the U.S. study and 94% in the European study.

As expected, patients receiving prophylactic therapy with folic acid had a lower incidence of liver function abnormalities. Elevated levels of alanine aminotransferase and aspartate aminotransferase were seen in 30% and 20%, respectively, of the patients in the U.S. study and in 63% and 47% of the patients in the European study.

But, “surprisingly,” patients in the U.S. study also had a higher incidence of symptomatic side effects (76%, vs. 68%), including a higher incidence of diarrhea, headache, and oral ulcers, compared with the European study group, the investigators reported.

The U.S. study involved 482 patients, 179 of whom received MTX and had RF data available. The European study involved 999 patients, 489 of whom received MTX and had RF data available.

The newly reported post hoc analysis combined all patients from both studies who were taking folic acid (50 from the European study, 175 from the U.S. study), as well as those who were not taking folic acid (439 in Europe and 4 in the U.S).

Patients who did not receive folic acid had a significantly lower mean body weight, a shorter mean duration of RA, and higher mean disease activity, as well as higher scores on the HAQ disability index and the Disease Activity Score in 28 joints (DAS28).

The mean dosage of MTX at 52 weeks was similar in the two trials, and oral folic acid was generally given in both studies at a dosage of 1–2 mg/day.

Use of concomitant folic acid significantly reduced the efficacy of methotrexate and did not decrease the overall incidence of symptomatic adverse events, according to the findings of a post hoc analysis.

The two phase III, randomized, controlled trials included in the analysis—one conducted in the United States and the other in Europe—compared the effects of 52 weeks of daily leflunomide with weekly methotrexate (MTX) in patients with active rheumatoid arthritis.

Although measuring the effect of folic acid was not the primary objective, the trials provided a look at its effect, because almost all of the patients in the MTX arm of the U.S. study—98%—were given daily folic acid, yet only 10% of the patients receiving MTX in the multinational European study received folate, each of them after they experienced an adverse event.

Previously published articles on the trials reported that 52% of patients in the MTX arm of the U.S. study achieved an American College of Rheumatology (ACR) 20 improvement response, compared with 65% of patients in the European trial.

Investigators of the new post hoc analysis set out to adjust for significant differences in the baseline characteristics of patients that made comparisons at 52 weeks “difficult to interpret,” explained Dinesh Khanna, M.D., of the University of Cincinnati and the Veterans Affairs Medical Center.

Using propensity score matching methods to adjust for these baseline differences, they found that folic acid use reduced the probability of an ACR 20 response by 15%–21%, or an average of 17%, in 225 patients who received the treatment compared with 443 patients who did not (Arthritis Rheum. 2005: 52;3030–38).

The results were consistent when comparing ACR 50 and ACR 70 improvement responses, the investigators said.

When they stratified patients by the presence or absence of rheumatoid factor, they found a statistical trend toward a lower ACR 20 response rate in the RF-negative group taking folic acid compared with the RF-positive group taking folic acid—a finding that “may suggest a preferential response to MTX in patients with active RA based on their RF status,” they said.

Adverse events were reported in 93% of patients in the U.S. study and 94% in the European study.

As expected, patients receiving prophylactic therapy with folic acid had a lower incidence of liver function abnormalities. Elevated levels of alanine aminotransferase and aspartate aminotransferase were seen in 30% and 20%, respectively, of the patients in the U.S. study and in 63% and 47% of the patients in the European study.

But, “surprisingly,” patients in the U.S. study also had a higher incidence of symptomatic side effects (76%, vs. 68%), including a higher incidence of diarrhea, headache, and oral ulcers, compared with the European study group, the investigators reported.

The U.S. study involved 482 patients, 179 of whom received MTX and had RF data available. The European study involved 999 patients, 489 of whom received MTX and had RF data available.

The newly reported post hoc analysis combined all patients from both studies who were taking folic acid (50 from the European study, 175 from the U.S. study), as well as those who were not taking folic acid (439 in Europe and 4 in the U.S).

Patients who did not receive folic acid had a significantly lower mean body weight, a shorter mean duration of RA, and higher mean disease activity, as well as higher scores on the HAQ disability index and the Disease Activity Score in 28 joints (DAS28).

The mean dosage of MTX at 52 weeks was similar in the two trials, and oral folic acid was generally given in both studies at a dosage of 1–2 mg/day.

Use of concomitant folic acid significantly reduced the efficacy of methotrexate and did not decrease the overall incidence of symptomatic adverse events, according to the findings of a post hoc analysis.

The two phase III, randomized, controlled trials included in the analysis—one conducted in the United States and the other in Europe—compared the effects of 52 weeks of daily leflunomide with weekly methotrexate (MTX) in patients with active rheumatoid arthritis.

Although measuring the effect of folic acid was not the primary objective, the trials provided a look at its effect, because almost all of the patients in the MTX arm of the U.S. study—98%—were given daily folic acid, yet only 10% of the patients receiving MTX in the multinational European study received folate, each of them after they experienced an adverse event.

Previously published articles on the trials reported that 52% of patients in the MTX arm of the U.S. study achieved an American College of Rheumatology (ACR) 20 improvement response, compared with 65% of patients in the European trial.

Investigators of the new post hoc analysis set out to adjust for significant differences in the baseline characteristics of patients that made comparisons at 52 weeks “difficult to interpret,” explained Dinesh Khanna, M.D., of the University of Cincinnati and the Veterans Affairs Medical Center.

Using propensity score matching methods to adjust for these baseline differences, they found that folic acid use reduced the probability of an ACR 20 response by 15%–21%, or an average of 17%, in 225 patients who received the treatment compared with 443 patients who did not (Arthritis Rheum. 2005: 52;3030–38).

The results were consistent when comparing ACR 50 and ACR 70 improvement responses, the investigators said.

When they stratified patients by the presence or absence of rheumatoid factor, they found a statistical trend toward a lower ACR 20 response rate in the RF-negative group taking folic acid compared with the RF-positive group taking folic acid—a finding that “may suggest a preferential response to MTX in patients with active RA based on their RF status,” they said.

Adverse events were reported in 93% of patients in the U.S. study and 94% in the European study.

As expected, patients receiving prophylactic therapy with folic acid had a lower incidence of liver function abnormalities. Elevated levels of alanine aminotransferase and aspartate aminotransferase were seen in 30% and 20%, respectively, of the patients in the U.S. study and in 63% and 47% of the patients in the European study.

But, “surprisingly,” patients in the U.S. study also had a higher incidence of symptomatic side effects (76%, vs. 68%), including a higher incidence of diarrhea, headache, and oral ulcers, compared with the European study group, the investigators reported.

The U.S. study involved 482 patients, 179 of whom received MTX and had RF data available. The European study involved 999 patients, 489 of whom received MTX and had RF data available.

The newly reported post hoc analysis combined all patients from both studies who were taking folic acid (50 from the European study, 175 from the U.S. study), as well as those who were not taking folic acid (439 in Europe and 4 in the U.S).

Patients who did not receive folic acid had a significantly lower mean body weight, a shorter mean duration of RA, and higher mean disease activity, as well as higher scores on the HAQ disability index and the Disease Activity Score in 28 joints (DAS28).

The mean dosage of MTX at 52 weeks was similar in the two trials, and oral folic acid was generally given in both studies at a dosage of 1–2 mg/day.

The compound clofazimine was as effective as chloroquine diphosphate in controlling active cutaneous lesions in patients with systemic lupus erythematosus who participated in a small randomized study.

The trial, which involved 33 patients, is the first randomized, controlled, double-blind study comparing the two drugs, as well as the first study of this indication for clofazimine, a riminophenazine compound that is stored for months in the fat and in the reticuloendothelial system in SLE patients, reported Elaine Lira Medeiros Bezerra, M.D., of the Universidade Federal do Rio Grande do Norte in Natal, Brazil, and her associates.

Clofazimine may be “indicated as a therapeutic option for lupus patients with exclusively cutaneous lesions and with contraindications to chloroquine,” they said (Arthritis Rheum. 2005;52:3073–8).

Although not statistically significant, most of the patients who were excluded from the study because of the development of an SLE flare were taking clofazimine, a finding that requires further investigation, they explained.

It's possible that clofazimine itself may have been the cause of the lupus flares, or that the difference in the frequency of flares between the two drug groups “might have been due to the known effect of chloroquine diphosphate in reducing lupus activity,” they said.

Of 33 patients enrolled in the study, 16 were randomized to receive 100 mg of clofazimine once a day for 6 months, and 17 were assigned to receive 250 mg of chloroquine once a day for 6 months. The drugs were placed into identical capsules.

The treatment groups were similar demographically and clinically. Patients in both groups received a broad-spectrum sunscreen twice a day, and prednisone doses were kept stable. The patients' lesions were evaluated by two blinded observers at baseline and throughout the study.

Based on an intent-to-treat analysis, 12 clofazimine-treated patients (75%) and 14 chloroquine-treated patients (82%) had complete or near-complete remission of their skin lesions, Dr. Bezerra and her associates reported.

Side effects—mainly skin and gastrointestinal events—were frequent but were “mild and tolerable,” they said.

Five clofazimine-treated patients were withdrawn after they developed a serious flare; all improved after treatment.

Another patient died about 4 months into the study after presenting with fever, seizures, and asymmetric paraparesis; the autopsy revealed infarction at the right choroid plexus and cerebral and cerebellum hemispheres, associated with a subarachnoid hemorrhage, the investigators reported.

One patient in the chloroquine group developed necrotizing vasculitis in the upper limbs and was withdrawn in the second month, they said.

The compound clofazimine was as effective as chloroquine diphosphate in controlling active cutaneous lesions in patients with systemic lupus erythematosus who participated in a small randomized study.

The trial, which involved 33 patients, is the first randomized, controlled, double-blind study comparing the two drugs, as well as the first study of this indication for clofazimine, a riminophenazine compound that is stored for months in the fat and in the reticuloendothelial system in SLE patients, reported Elaine Lira Medeiros Bezerra, M.D., of the Universidade Federal do Rio Grande do Norte in Natal, Brazil, and her associates.

Clofazimine may be “indicated as a therapeutic option for lupus patients with exclusively cutaneous lesions and with contraindications to chloroquine,” they said (Arthritis Rheum. 2005;52:3073–8).

Although not statistically significant, most of the patients who were excluded from the study because of the development of an SLE flare were taking clofazimine, a finding that requires further investigation, they explained.

It's possible that clofazimine itself may have been the cause of the lupus flares, or that the difference in the frequency of flares between the two drug groups “might have been due to the known effect of chloroquine diphosphate in reducing lupus activity,” they said.

Of 33 patients enrolled in the study, 16 were randomized to receive 100 mg of clofazimine once a day for 6 months, and 17 were assigned to receive 250 mg of chloroquine once a day for 6 months. The drugs were placed into identical capsules.

The treatment groups were similar demographically and clinically. Patients in both groups received a broad-spectrum sunscreen twice a day, and prednisone doses were kept stable. The patients' lesions were evaluated by two blinded observers at baseline and throughout the study.

Based on an intent-to-treat analysis, 12 clofazimine-treated patients (75%) and 14 chloroquine-treated patients (82%) had complete or near-complete remission of their skin lesions, Dr. Bezerra and her associates reported.

Side effects—mainly skin and gastrointestinal events—were frequent but were “mild and tolerable,” they said.

Five clofazimine-treated patients were withdrawn after they developed a serious flare; all improved after treatment.

Another patient died about 4 months into the study after presenting with fever, seizures, and asymmetric paraparesis; the autopsy revealed infarction at the right choroid plexus and cerebral and cerebellum hemispheres, associated with a subarachnoid hemorrhage, the investigators reported.

One patient in the chloroquine group developed necrotizing vasculitis in the upper limbs and was withdrawn in the second month, they said.

The compound clofazimine was as effective as chloroquine diphosphate in controlling active cutaneous lesions in patients with systemic lupus erythematosus who participated in a small randomized study.

The trial, which involved 33 patients, is the first randomized, controlled, double-blind study comparing the two drugs, as well as the first study of this indication for clofazimine, a riminophenazine compound that is stored for months in the fat and in the reticuloendothelial system in SLE patients, reported Elaine Lira Medeiros Bezerra, M.D., of the Universidade Federal do Rio Grande do Norte in Natal, Brazil, and her associates.

Clofazimine may be “indicated as a therapeutic option for lupus patients with exclusively cutaneous lesions and with contraindications to chloroquine,” they said (Arthritis Rheum. 2005;52:3073–8).

Although not statistically significant, most of the patients who were excluded from the study because of the development of an SLE flare were taking clofazimine, a finding that requires further investigation, they explained.

It's possible that clofazimine itself may have been the cause of the lupus flares, or that the difference in the frequency of flares between the two drug groups “might have been due to the known effect of chloroquine diphosphate in reducing lupus activity,” they said.

Of 33 patients enrolled in the study, 16 were randomized to receive 100 mg of clofazimine once a day for 6 months, and 17 were assigned to receive 250 mg of chloroquine once a day for 6 months. The drugs were placed into identical capsules.

The treatment groups were similar demographically and clinically. Patients in both groups received a broad-spectrum sunscreen twice a day, and prednisone doses were kept stable. The patients' lesions were evaluated by two blinded observers at baseline and throughout the study.

Based on an intent-to-treat analysis, 12 clofazimine-treated patients (75%) and 14 chloroquine-treated patients (82%) had complete or near-complete remission of their skin lesions, Dr. Bezerra and her associates reported.

Side effects—mainly skin and gastrointestinal events—were frequent but were “mild and tolerable,” they said.

Five clofazimine-treated patients were withdrawn after they developed a serious flare; all improved after treatment.

Another patient died about 4 months into the study after presenting with fever, seizures, and asymmetric paraparesis; the autopsy revealed infarction at the right choroid plexus and cerebral and cerebellum hemispheres, associated with a subarachnoid hemorrhage, the investigators reported.

One patient in the chloroquine group developed necrotizing vasculitis in the upper limbs and was withdrawn in the second month, they said.