Christine Kilgore

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.

Multifocal tumors in papillary thyroid cancer appear to often arise as independent tumors—a finding that supports the use of bilateral thyroidectomy and radioablation of remaining tissue, according to Trisha M. Shattuck of the University of Connecticut, Farmington, and her associates.

Papillary thyroid carcinoma is the most common cancer of the thyroid gland, and it is often multifocal—typically with a “primary” tumor greater than 1 cm in diameter and additional, much smaller “microcarcinomas.”

Multifocal carcinomas have been associated with increased risks of lymph-node and distant metastases, persistent local disease after initial treatments, and regional recurrence—features that have suggested that patients be treated aggressively.

It has been unclear, however, whether multiple intrathyroid tumors are metastases of a primary tumor or whether they arise independently as individual carcinomas, the investigators said (N. Engl. J. Med. 2005;352:2406–12).

They examined tumor samples from 17 women with multifocal papillary thyroid carcinoma who underwent thyroidectomy. Using a polymerase chain reaction (PCR) assay involving the human androgen receptor gene, they analyzed tumor DNA for patterns of X-chromosome inactivation (inactivation of either the maternal or paternal X-chromosome).

Such patterns can be used to determine whether a tumor arose from one or multiple progenitor cells because the inactivated chromosome is stably transmitted from parent cell to progeny cell, the investigators explained.

Multiple tumor foci from 10 of the 17 patients were suitable for analysis; they yielded DNA of adequate quality and quantity and were heterozygous for the human androgen receptor gene polymorphism. A single X chromosome was inactivated in each focus, the investigators reported.

Tumors from 5 of the 10 patients showed discordant patterns of X-chromosome inactivation that indicated the tumors arose separately from different progenitor cells. Tumors in the other five patients showed patterns that could be interpreted as indicating either a shared or independent origin.

The findings “favor the independent clonal origins of the distinct foci in some [and possibly most] of these cases,” according to the investigators.

The findings also “imply that any thyroid tissue remaining after surgery to treat papillary thyroid cancer in patients with multifocal disease may contain—or be likely to develop—additional foci of cancer that could become recurrences.”

In an editorial, Robert D. Utiger, M.D., wrote that the evidence “supports the clinical finding that patients with papillary carcinoma who undergo thyroid lobectomy are more likely than those who undergo near total thyroidectomy to have recurrent carcinoma in the remaining lobe as well as elsewhere.”

Annual estimates of thyroid cancer diagnoses have been growing faster than the population for several decades, and the proportion of these cancers that are papillary carcinomas is growing as well, said Dr. Utiger of Harvard Medical School, Boston (N. Engl. J. Med. 2005;352:2376–8).

Multifocal tumors in papillary thyroid cancer appear to often arise as independent tumors—a finding that supports the use of bilateral thyroidectomy and radioablation of remaining tissue, according to Trisha M. Shattuck of the University of Connecticut, Farmington, and her associates.

Papillary thyroid carcinoma is the most common cancer of the thyroid gland, and it is often multifocal—typically with a “primary” tumor greater than 1 cm in diameter and additional, much smaller “microcarcinomas.”

Multifocal carcinomas have been associated with increased risks of lymph-node and distant metastases, persistent local disease after initial treatments, and regional recurrence—features that have suggested that patients be treated aggressively.

It has been unclear, however, whether multiple intrathyroid tumors are metastases of a primary tumor or whether they arise independently as individual carcinomas, the investigators said (N. Engl. J. Med. 2005;352:2406–12).

They examined tumor samples from 17 women with multifocal papillary thyroid carcinoma who underwent thyroidectomy. Using a polymerase chain reaction (PCR) assay involving the human androgen receptor gene, they analyzed tumor DNA for patterns of X-chromosome inactivation (inactivation of either the maternal or paternal X-chromosome).

Such patterns can be used to determine whether a tumor arose from one or multiple progenitor cells because the inactivated chromosome is stably transmitted from parent cell to progeny cell, the investigators explained.

Multiple tumor foci from 10 of the 17 patients were suitable for analysis; they yielded DNA of adequate quality and quantity and were heterozygous for the human androgen receptor gene polymorphism. A single X chromosome was inactivated in each focus, the investigators reported.

Tumors from 5 of the 10 patients showed discordant patterns of X-chromosome inactivation that indicated the tumors arose separately from different progenitor cells. Tumors in the other five patients showed patterns that could be interpreted as indicating either a shared or independent origin.

The findings “favor the independent clonal origins of the distinct foci in some [and possibly most] of these cases,” according to the investigators.

The findings also “imply that any thyroid tissue remaining after surgery to treat papillary thyroid cancer in patients with multifocal disease may contain—or be likely to develop—additional foci of cancer that could become recurrences.”

In an editorial, Robert D. Utiger, M.D., wrote that the evidence “supports the clinical finding that patients with papillary carcinoma who undergo thyroid lobectomy are more likely than those who undergo near total thyroidectomy to have recurrent carcinoma in the remaining lobe as well as elsewhere.”

Annual estimates of thyroid cancer diagnoses have been growing faster than the population for several decades, and the proportion of these cancers that are papillary carcinomas is growing as well, said Dr. Utiger of Harvard Medical School, Boston (N. Engl. J. Med. 2005;352:2376–8).

Multifocal tumors in papillary thyroid cancer appear to often arise as independent tumors—a finding that supports the use of bilateral thyroidectomy and radioablation of remaining tissue, according to Trisha M. Shattuck of the University of Connecticut, Farmington, and her associates.

Papillary thyroid carcinoma is the most common cancer of the thyroid gland, and it is often multifocal—typically with a “primary” tumor greater than 1 cm in diameter and additional, much smaller “microcarcinomas.”

Multifocal carcinomas have been associated with increased risks of lymph-node and distant metastases, persistent local disease after initial treatments, and regional recurrence—features that have suggested that patients be treated aggressively.

It has been unclear, however, whether multiple intrathyroid tumors are metastases of a primary tumor or whether they arise independently as individual carcinomas, the investigators said (N. Engl. J. Med. 2005;352:2406–12).

They examined tumor samples from 17 women with multifocal papillary thyroid carcinoma who underwent thyroidectomy. Using a polymerase chain reaction (PCR) assay involving the human androgen receptor gene, they analyzed tumor DNA for patterns of X-chromosome inactivation (inactivation of either the maternal or paternal X-chromosome).

Such patterns can be used to determine whether a tumor arose from one or multiple progenitor cells because the inactivated chromosome is stably transmitted from parent cell to progeny cell, the investigators explained.

Multiple tumor foci from 10 of the 17 patients were suitable for analysis; they yielded DNA of adequate quality and quantity and were heterozygous for the human androgen receptor gene polymorphism. A single X chromosome was inactivated in each focus, the investigators reported.

Tumors from 5 of the 10 patients showed discordant patterns of X-chromosome inactivation that indicated the tumors arose separately from different progenitor cells. Tumors in the other five patients showed patterns that could be interpreted as indicating either a shared or independent origin.

The findings “favor the independent clonal origins of the distinct foci in some [and possibly most] of these cases,” according to the investigators.

The findings also “imply that any thyroid tissue remaining after surgery to treat papillary thyroid cancer in patients with multifocal disease may contain—or be likely to develop—additional foci of cancer that could become recurrences.”

In an editorial, Robert D. Utiger, M.D., wrote that the evidence “supports the clinical finding that patients with papillary carcinoma who undergo thyroid lobectomy are more likely than those who undergo near total thyroidectomy to have recurrent carcinoma in the remaining lobe as well as elsewhere.”

Annual estimates of thyroid cancer diagnoses have been growing faster than the population for several decades, and the proportion of these cancers that are papillary carcinomas is growing as well, said Dr. Utiger of Harvard Medical School, Boston (N. Engl. J. Med. 2005;352:2376–8).

Women treated for hypothyroidism were less likely to develop primary breast carcinoma—and more likely to have more indolent disease when they did develop cancer—than women with normal thyroid function in a retrospective, case-control study.

The findings “strengthen the possibility of a significant role of thyroid hormones on breast cancer biology” and may indicate areas of intervention “for targeted preventive and therapeutic purposes,” said Massimo Cristofanilli, M.D., and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

The investigators compared the medical records from 1,136 women with primary breast carcinoma with those of 1,088 healthy women who visited their breast cancer-screening clinic.

Approximately 240 women reported having symptomatic primary hypothyroidism and thyroid supplementation before they were diagnosed with breast cancer or before their screening visit.

The prevalence of reported hypothyroidism was significantly greater in the control group, compared with the breast cancer group (15% vs. 7%).

Women with primary hypothyroidism had a 61% lower risk of developing invasive breast cancer, and women with breast cancer were 57% less likely to have hypothyroidism, compared with healthy women, the investigators reported (Cancer 2005;103:1122–8).

After adjustment for confounders of breast cancer risk such as family history of breast carcinoma and history of pregnancy, the association between breast cancer and hypothyroidism “essentially was unchanged and [treated hypothyroidism] remained a strong protective factor against a diagnosis of invasive breast carcinoma,” they said. The association was similar in all ethnic groups.

Among women with invasive breast cancer, patients with hypothyroidism were older at the time of diagnosis (59 vs. 51 years) and were more likely to be postmenopausal (82% vs. 64%) than patients with normal thyroid function.

Among white women specifically, those with invasive cancer who had been treated for hypothyroidism were more likely to be diagnosed with early-stage disease (95% vs. 86%) and disease without pathologic lymph node involvement (64% vs. 56%).

They also had smaller pathologic tumor size than women with invasive cancer but normal thyroid function.

The investigators restricted part of their analysis to white women to have a more homogenous population and to eliminate the influence of ethnicity.

A possible association between thyroid disease and breast carcinoma has been debated for decades and remains controversial, the investigators say. Epidemiologic studies have had conflicting results, and large prospective studies have failed to clearly demonstrate a correlation.

Women treated for hypothyroidism were less likely to develop primary breast carcinoma—and more likely to have more indolent disease when they did develop cancer—than women with normal thyroid function in a retrospective, case-control study.

The findings “strengthen the possibility of a significant role of thyroid hormones on breast cancer biology” and may indicate areas of intervention “for targeted preventive and therapeutic purposes,” said Massimo Cristofanilli, M.D., and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

The investigators compared the medical records from 1,136 women with primary breast carcinoma with those of 1,088 healthy women who visited their breast cancer-screening clinic.

Approximately 240 women reported having symptomatic primary hypothyroidism and thyroid supplementation before they were diagnosed with breast cancer or before their screening visit.

The prevalence of reported hypothyroidism was significantly greater in the control group, compared with the breast cancer group (15% vs. 7%).

Women with primary hypothyroidism had a 61% lower risk of developing invasive breast cancer, and women with breast cancer were 57% less likely to have hypothyroidism, compared with healthy women, the investigators reported (Cancer 2005;103:1122–8).

After adjustment for confounders of breast cancer risk such as family history of breast carcinoma and history of pregnancy, the association between breast cancer and hypothyroidism “essentially was unchanged and [treated hypothyroidism] remained a strong protective factor against a diagnosis of invasive breast carcinoma,” they said. The association was similar in all ethnic groups.

Among women with invasive breast cancer, patients with hypothyroidism were older at the time of diagnosis (59 vs. 51 years) and were more likely to be postmenopausal (82% vs. 64%) than patients with normal thyroid function.

Among white women specifically, those with invasive cancer who had been treated for hypothyroidism were more likely to be diagnosed with early-stage disease (95% vs. 86%) and disease without pathologic lymph node involvement (64% vs. 56%).

They also had smaller pathologic tumor size than women with invasive cancer but normal thyroid function.

The investigators restricted part of their analysis to white women to have a more homogenous population and to eliminate the influence of ethnicity.

A possible association between thyroid disease and breast carcinoma has been debated for decades and remains controversial, the investigators say. Epidemiologic studies have had conflicting results, and large prospective studies have failed to clearly demonstrate a correlation.

Women treated for hypothyroidism were less likely to develop primary breast carcinoma—and more likely to have more indolent disease when they did develop cancer—than women with normal thyroid function in a retrospective, case-control study.

The findings “strengthen the possibility of a significant role of thyroid hormones on breast cancer biology” and may indicate areas of intervention “for targeted preventive and therapeutic purposes,” said Massimo Cristofanilli, M.D., and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

The investigators compared the medical records from 1,136 women with primary breast carcinoma with those of 1,088 healthy women who visited their breast cancer-screening clinic.

Approximately 240 women reported having symptomatic primary hypothyroidism and thyroid supplementation before they were diagnosed with breast cancer or before their screening visit.

The prevalence of reported hypothyroidism was significantly greater in the control group, compared with the breast cancer group (15% vs. 7%).

Women with primary hypothyroidism had a 61% lower risk of developing invasive breast cancer, and women with breast cancer were 57% less likely to have hypothyroidism, compared with healthy women, the investigators reported (Cancer 2005;103:1122–8).

After adjustment for confounders of breast cancer risk such as family history of breast carcinoma and history of pregnancy, the association between breast cancer and hypothyroidism “essentially was unchanged and [treated hypothyroidism] remained a strong protective factor against a diagnosis of invasive breast carcinoma,” they said. The association was similar in all ethnic groups.

Among women with invasive breast cancer, patients with hypothyroidism were older at the time of diagnosis (59 vs. 51 years) and were more likely to be postmenopausal (82% vs. 64%) than patients with normal thyroid function.

Among white women specifically, those with invasive cancer who had been treated for hypothyroidism were more likely to be diagnosed with early-stage disease (95% vs. 86%) and disease without pathologic lymph node involvement (64% vs. 56%).

They also had smaller pathologic tumor size than women with invasive cancer but normal thyroid function.

The investigators restricted part of their analysis to white women to have a more homogenous population and to eliminate the influence of ethnicity.

A possible association between thyroid disease and breast carcinoma has been debated for decades and remains controversial, the investigators say. Epidemiologic studies have had conflicting results, and large prospective studies have failed to clearly demonstrate a correlation.

Less than a month after two major diabetes organizations called metabolic syndrome a poorly defined and misleading diagnosis, the American Heart Association and the National Heart, Lung, and Blood Institute issued a joint statement reaffirming that the syndrome is valid and clinically useful.

The new AHA/NHLBI scientific statement basically confirms the recommendations on diagnosis and management of metabolic syndrome that were issued in 2001 as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) report.

The statement also clarifies some issues and provides some minor modifications to the ATP III definition of the metabolic syndrome—a term that denotes the clustering of interrelated metabolic risk factors for atherosclerotic cardiovascular disease.

Compared with the joint statement published last month by the American Diabetes Association and the European Association for the Study of Diabetes (“Term 'Metabolic Syndrome' Called Into Question,” FAMILY PRACTICE NEWS, Sept. 1, 2005, p. 5), the AHA/NHLBI statement offers a clearly different perspective on the meaning and value of a term that's now commonplace in the medical literature.

“Metabolic syndrome is a valuable clinical tool. Physicians must pay attention to it, and they must give enough attention to lifestyle (intervention),” said Scott M. Grundy, M.D., director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas. Dr. Grundy chaired the panel that wrote the joint statement.

While the diabetes organizations questioned the value of the syndrome as a predictor of cardiovascular disease—they said, for instance, that it's “uncertain” whether it's a useful marker of cardiovascular disease risk “above and beyond the risks associated with its individual components”—the AHA/NHLBI panel maintained that it's an important and useful predictor.

The absolute short-term (10-year) risk for major coronary heart disease events is not necessarily high—and may be best assessed by Framingham risk scoring—but the longer-term risk associated with the metabolic syndrome is “undoubtedly” elevated, regardless of the Framingham score, the panel said (Circulation 2005;DOI:10.1161/circ ulationaha.105.169404).

“The long-term risk is more than the sum of the parts—the risk multiplies,” said Dr. Grundy.

“Nobody is asserting that metabolic syndrome is a disease. No one is saying it's a unified entity. It's a group of factors that tend to cluster together, and the diagnosis gives physicians an opportunity to identify people at long-term risk,” said James I. Cleeman, M.D., cochair of the panel and coordinator of the NHLBI's National Cholesterol Education Program.

“There's no question that risk increases when these risk factors (cluster),” he said in an interview.

Overall, the syndrome increases the risk for atherosclerotic cardiovascular disease 1.5–3 times and raises the risk for type 2 diabetes 3–5 times, he and Dr. Grundy said in an interview. The new statement essentially “ties up loose ends” and synthesizes information presented at NIH-sponsored conferences held after the ATP III report was released.

The statement maintains the same diagnostic criteria for metabolic syndrome—elevated waist circumference, elevated triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose—and the requirement that three of the five criteria be present for a diagnosis.

It also offers the following modifications and clarifications:

▸ The threshold for elevated fasting glucose is reduced from 110 to 100 mg/dL, in accordance with the ADA's recently revised definition.

▸ Triglycerides, HDL-C levels, and blood pressure may be counted as abnormal when a patient is taking drug treatment for these factors.

▸ The threshold for waist circumference (102 cm in men and 88 cm in women) may be lowered in individuals or ethnic groups, particularly Asian Americans, who are prone to insulin resistance.

The panel maintained that individuals who have established atherosclerotic cardiovascular disease or type 2 diabetes can still have the metabolic syndrome—a position that is at odds with the ADA-EASD statement.

The modified ATP III definition is almost identical to the definition released—also last month—by the International Diabetes Federation, Dr. Cleeman said. One difference is that the IDF requires the presence of abdominal obesity for diagnosis.

More research is needed on the most appropriate therapies for patients with the metabolic syndrome, but for now the “prime emphasis” should be on lifestyle interventions, the joint statement said. Drug therapies for specific risk factors “may be indicated” when lifestyle changes are not sufficient.

It cautions, however, against prescribing drugs that purportedly target underlying causes of the syndrome (namely obesity and insulin resistance) until evidence is sufficient.

While the AHA/NHLBI statement was in the works before the ADA and EASD released their joint statement, the effort by the diabetes organizations sent at least one other group scrambling.

The American Association of Clinical Endocrinologists last month had a “rapid-response task force” reviewing its 2003 position paper on what it calls the “insulin resistance syndrome.”

“With the critical appraisal by the ADA, we want a well-thought-out, evidence-based response to clarify our position (on the issue),” said Jeffrey I. Mechanick, M.D., an endocrinologist who is leading the task force.

Less than a month after two major diabetes organizations called metabolic syndrome a poorly defined and misleading diagnosis, the American Heart Association and the National Heart, Lung, and Blood Institute issued a joint statement reaffirming that the syndrome is valid and clinically useful.

The new AHA/NHLBI scientific statement basically confirms the recommendations on diagnosis and management of metabolic syndrome that were issued in 2001 as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) report.

The statement also clarifies some issues and provides some minor modifications to the ATP III definition of the metabolic syndrome—a term that denotes the clustering of interrelated metabolic risk factors for atherosclerotic cardiovascular disease.

Compared with the joint statement published last month by the American Diabetes Association and the European Association for the Study of Diabetes (“Term 'Metabolic Syndrome' Called Into Question,” FAMILY PRACTICE NEWS, Sept. 1, 2005, p. 5), the AHA/NHLBI statement offers a clearly different perspective on the meaning and value of a term that's now commonplace in the medical literature.

“Metabolic syndrome is a valuable clinical tool. Physicians must pay attention to it, and they must give enough attention to lifestyle (intervention),” said Scott M. Grundy, M.D., director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas. Dr. Grundy chaired the panel that wrote the joint statement.

While the diabetes organizations questioned the value of the syndrome as a predictor of cardiovascular disease—they said, for instance, that it's “uncertain” whether it's a useful marker of cardiovascular disease risk “above and beyond the risks associated with its individual components”—the AHA/NHLBI panel maintained that it's an important and useful predictor.

The absolute short-term (10-year) risk for major coronary heart disease events is not necessarily high—and may be best assessed by Framingham risk scoring—but the longer-term risk associated with the metabolic syndrome is “undoubtedly” elevated, regardless of the Framingham score, the panel said (Circulation 2005;DOI:10.1161/circ ulationaha.105.169404).

“The long-term risk is more than the sum of the parts—the risk multiplies,” said Dr. Grundy.

“Nobody is asserting that metabolic syndrome is a disease. No one is saying it's a unified entity. It's a group of factors that tend to cluster together, and the diagnosis gives physicians an opportunity to identify people at long-term risk,” said James I. Cleeman, M.D., cochair of the panel and coordinator of the NHLBI's National Cholesterol Education Program.

“There's no question that risk increases when these risk factors (cluster),” he said in an interview.

Overall, the syndrome increases the risk for atherosclerotic cardiovascular disease 1.5–3 times and raises the risk for type 2 diabetes 3–5 times, he and Dr. Grundy said in an interview. The new statement essentially “ties up loose ends” and synthesizes information presented at NIH-sponsored conferences held after the ATP III report was released.

The statement maintains the same diagnostic criteria for metabolic syndrome—elevated waist circumference, elevated triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose—and the requirement that three of the five criteria be present for a diagnosis.

It also offers the following modifications and clarifications:

▸ The threshold for elevated fasting glucose is reduced from 110 to 100 mg/dL, in accordance with the ADA's recently revised definition.

▸ Triglycerides, HDL-C levels, and blood pressure may be counted as abnormal when a patient is taking drug treatment for these factors.

▸ The threshold for waist circumference (102 cm in men and 88 cm in women) may be lowered in individuals or ethnic groups, particularly Asian Americans, who are prone to insulin resistance.

The panel maintained that individuals who have established atherosclerotic cardiovascular disease or type 2 diabetes can still have the metabolic syndrome—a position that is at odds with the ADA-EASD statement.

The modified ATP III definition is almost identical to the definition released—also last month—by the International Diabetes Federation, Dr. Cleeman said. One difference is that the IDF requires the presence of abdominal obesity for diagnosis.

More research is needed on the most appropriate therapies for patients with the metabolic syndrome, but for now the “prime emphasis” should be on lifestyle interventions, the joint statement said. Drug therapies for specific risk factors “may be indicated” when lifestyle changes are not sufficient.

It cautions, however, against prescribing drugs that purportedly target underlying causes of the syndrome (namely obesity and insulin resistance) until evidence is sufficient.

While the AHA/NHLBI statement was in the works before the ADA and EASD released their joint statement, the effort by the diabetes organizations sent at least one other group scrambling.

The American Association of Clinical Endocrinologists last month had a “rapid-response task force” reviewing its 2003 position paper on what it calls the “insulin resistance syndrome.”

“With the critical appraisal by the ADA, we want a well-thought-out, evidence-based response to clarify our position (on the issue),” said Jeffrey I. Mechanick, M.D., an endocrinologist who is leading the task force.

Less than a month after two major diabetes organizations called metabolic syndrome a poorly defined and misleading diagnosis, the American Heart Association and the National Heart, Lung, and Blood Institute issued a joint statement reaffirming that the syndrome is valid and clinically useful.

The new AHA/NHLBI scientific statement basically confirms the recommendations on diagnosis and management of metabolic syndrome that were issued in 2001 as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) report.

The statement also clarifies some issues and provides some minor modifications to the ATP III definition of the metabolic syndrome—a term that denotes the clustering of interrelated metabolic risk factors for atherosclerotic cardiovascular disease.

Compared with the joint statement published last month by the American Diabetes Association and the European Association for the Study of Diabetes (“Term 'Metabolic Syndrome' Called Into Question,” FAMILY PRACTICE NEWS, Sept. 1, 2005, p. 5), the AHA/NHLBI statement offers a clearly different perspective on the meaning and value of a term that's now commonplace in the medical literature.

“Metabolic syndrome is a valuable clinical tool. Physicians must pay attention to it, and they must give enough attention to lifestyle (intervention),” said Scott M. Grundy, M.D., director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas. Dr. Grundy chaired the panel that wrote the joint statement.

While the diabetes organizations questioned the value of the syndrome as a predictor of cardiovascular disease—they said, for instance, that it's “uncertain” whether it's a useful marker of cardiovascular disease risk “above and beyond the risks associated with its individual components”—the AHA/NHLBI panel maintained that it's an important and useful predictor.

The absolute short-term (10-year) risk for major coronary heart disease events is not necessarily high—and may be best assessed by Framingham risk scoring—but the longer-term risk associated with the metabolic syndrome is “undoubtedly” elevated, regardless of the Framingham score, the panel said (Circulation 2005;DOI:10.1161/circ ulationaha.105.169404).

“The long-term risk is more than the sum of the parts—the risk multiplies,” said Dr. Grundy.

“Nobody is asserting that metabolic syndrome is a disease. No one is saying it's a unified entity. It's a group of factors that tend to cluster together, and the diagnosis gives physicians an opportunity to identify people at long-term risk,” said James I. Cleeman, M.D., cochair of the panel and coordinator of the NHLBI's National Cholesterol Education Program.

“There's no question that risk increases when these risk factors (cluster),” he said in an interview.

Overall, the syndrome increases the risk for atherosclerotic cardiovascular disease 1.5–3 times and raises the risk for type 2 diabetes 3–5 times, he and Dr. Grundy said in an interview. The new statement essentially “ties up loose ends” and synthesizes information presented at NIH-sponsored conferences held after the ATP III report was released.

The statement maintains the same diagnostic criteria for metabolic syndrome—elevated waist circumference, elevated triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose—and the requirement that three of the five criteria be present for a diagnosis.

It also offers the following modifications and clarifications:

▸ The threshold for elevated fasting glucose is reduced from 110 to 100 mg/dL, in accordance with the ADA's recently revised definition.

▸ Triglycerides, HDL-C levels, and blood pressure may be counted as abnormal when a patient is taking drug treatment for these factors.

▸ The threshold for waist circumference (102 cm in men and 88 cm in women) may be lowered in individuals or ethnic groups, particularly Asian Americans, who are prone to insulin resistance.

The panel maintained that individuals who have established atherosclerotic cardiovascular disease or type 2 diabetes can still have the metabolic syndrome—a position that is at odds with the ADA-EASD statement.

The modified ATP III definition is almost identical to the definition released—also last month—by the International Diabetes Federation, Dr. Cleeman said. One difference is that the IDF requires the presence of abdominal obesity for diagnosis.

More research is needed on the most appropriate therapies for patients with the metabolic syndrome, but for now the “prime emphasis” should be on lifestyle interventions, the joint statement said. Drug therapies for specific risk factors “may be indicated” when lifestyle changes are not sufficient.

It cautions, however, against prescribing drugs that purportedly target underlying causes of the syndrome (namely obesity and insulin resistance) until evidence is sufficient.

While the AHA/NHLBI statement was in the works before the ADA and EASD released their joint statement, the effort by the diabetes organizations sent at least one other group scrambling.

The American Association of Clinical Endocrinologists last month had a “rapid-response task force” reviewing its 2003 position paper on what it calls the “insulin resistance syndrome.”

“With the critical appraisal by the ADA, we want a well-thought-out, evidence-based response to clarify our position (on the issue),” said Jeffrey I. Mechanick, M.D., an endocrinologist who is leading the task force.

Findings from a national study of access to trauma centers vividly illustrate what many have suspected—some Americans have access to large numbers of trauma centers, while others have access to none.

Now, say leaders in emergency medicine, it's time to collect even more data and look more earnestly at how trauma care can be improved—not only by modifying the often politically driven placement of centers and transport, but also by examining and acting on issues of quality of care, financing, and manpower.

“This is very much a tip-of-the-iceberg analysis. [Access to trauma centers] is a huge issue, and it's important to get [these data] out there,” said Gregory Luke Larkin, M.D., immediate past chair of the American College of Emergency Physicians' Trauma and Injury Prevention Committee. Hopefully, the analysis will generate momentum in looking at access and other related issues, he added.

“It should be just the beginning of a conversation about trauma care,” said Dr. Larkin, professor of surgery, emergency medicine, and public health at the University of Texas Southwestern Medical Center at Dallas. “And it should give permission for folks to talk about it at a national level,” as well as within states, he said.

The investigators of the cross-sectional study, published last month in the Journal of the American Medical Association, found that almost 70% of all U.S. residents had access to a level I or level II trauma center within 45 minutes, and that approximately 84% had access within 60 minutes.

While almost 43 million of these residents—most living in urban areas—had access within an hour to 20 or more level I or II centers, almost 47 million—most in rural areas—had no such access to any centers.

Only 8% of rural residents—compared with 73% of suburban populations and 89% of urban populations—had access to level I and level II centers within 45 minutes. The percentages increased to 24%, 86%, and 95% when the time parameter was 60 minutes, the investigators reported (JAMA 2005:293;2626–33).

Beyond the Obvious

The study reveals much of “what we all knew intuitively,” said Jon R. Krohmer, M.D., medical director of Kent County EMS in Grand Rapids, Mich., and the ACEP liaison to the American College of Surgeons' Committee on Trauma.

It's significantly “innovative,” however, because the data sources are new and because investigators evaluated access in terms of population, as opposed to land area only. The researchers also measured access in terms of “prehospital time”—the time from receipt of an emergency call to hospital arrival—as opposed to distance or pure “transport time,” Dr. Krohmer said.

The investigators mainly used the January 2005 Trauma Center Inventory verified by the ACS Committee on Trauma, and the January 2005 version of the Atlas and Database of Air Medical Services.

“The study points out very graphically that there are areas that are potentially overserved, and areas that aren't served at all,” said Dr. Krohmer, an attending physician at Spectrum Health and medical director of Kent County EMS, both in Grand Rapids, Mich.

So, would a level I trauma center ever be built in Big Piney, Wyoming? “That's the million-dollar question,” he said. “And that's why this study should be the basis for future studies on quality of care and outcomes.

“We've asked, for instance, what is a minimal or acceptable patient volume to support a level I center? And right now, we don't have good answers,” Dr. Krohmer said.

Accessing Solutions

In their comments, the investigators question whether the access of some Americans to multiple trauma centers may be excessive, and whether “appropriate limits” on the number of centers could increase patient volumes and thus improve the quality of care—questions that both Dr. Krohmer and Dr. Larkin said are good ones.

The authors also emphasize the finding that 27% and 28% of U.S. residents had access—within 45 and 60 minutes, respectively—to level I and II centers by helicopter only.

“This, and the fact that base helipads are more moveable … makes them appealing as modifiable components of the trauma system,” wrote Charles C. Branas, Ph.D., an epidemiologist at the University of Pennsylvania, Philadelphia, and his associates.

National leadership on trauma care issues should also be better funded and more extensive, though “at this point, states need to get their systems (better) developed,” Dr. Branas told ACEP NEWS. States also need to make or strengthen arrangements for border crossings for day-to-day trauma care, he and his associates wrote.

Approximately 2%–3% of U.S. residents had access to level I and II trauma centers only via the centers and helicopters of neighboring states, the study showed. Most of the standardized interstate agreements for sharing resources, however, concern mass casualty incidents rather than day-to-day trauma care, the investigators said.

Dr. Larkin said he agrees that more “well-institutionalized” interstate arrangements are needed. He said he worries, on the other hand, that the potential of helicopters—which he said are now too often “big billboards for hospitals”—will be overstated and used as part of a cookie-cutter approach to solving access discrepancies.

He would rather see investigators and policymakers pair the new data on access with epidemiologic data—looking, for instance, at where motor vehicle crashes (the most common cause of trauma) occur most frequently.

“I hope people don't misread the data and assume it's the last word on trauma care,” said Dr. Larkin. “There is a whole host of other issues that need to be addressed.”

These include the issue of financing trauma care, a significant portion of which goes unpaid for, and issues of manpower and varying “densities” across the country of board-certified trauma surgeons and emergency physicians, he said.

Dr. Larkin emphasized that there's “a pretty big difference between level I and level II centers.” He advised paying more attention to access within 45 minutes than to access within the 60-minute time frame, since—as the investigators also point out—the so-called golden hour cutoff is supported by little scientific evidence and is probably too long.

Because the study excluded pediatric trauma centers and did not stratify access by age, the findings understate the access problems faced by the younger population, Dr. Larkin noted. “Trauma,” he said, “is the most common cause of death in the first four decades.”

Findings from a national study of access to trauma centers vividly illustrate what many have suspected—some Americans have access to large numbers of trauma centers, while others have access to none.

Now, say leaders in emergency medicine, it's time to collect even more data and look more earnestly at how trauma care can be improved—not only by modifying the often politically driven placement of centers and transport, but also by examining and acting on issues of quality of care, financing, and manpower.

“This is very much a tip-of-the-iceberg analysis. [Access to trauma centers] is a huge issue, and it's important to get [these data] out there,” said Gregory Luke Larkin, M.D., immediate past chair of the American College of Emergency Physicians' Trauma and Injury Prevention Committee. Hopefully, the analysis will generate momentum in looking at access and other related issues, he added.

“It should be just the beginning of a conversation about trauma care,” said Dr. Larkin, professor of surgery, emergency medicine, and public health at the University of Texas Southwestern Medical Center at Dallas. “And it should give permission for folks to talk about it at a national level,” as well as within states, he said.

The investigators of the cross-sectional study, published last month in the Journal of the American Medical Association, found that almost 70% of all U.S. residents had access to a level I or level II trauma center within 45 minutes, and that approximately 84% had access within 60 minutes.

While almost 43 million of these residents—most living in urban areas—had access within an hour to 20 or more level I or II centers, almost 47 million—most in rural areas—had no such access to any centers.

Only 8% of rural residents—compared with 73% of suburban populations and 89% of urban populations—had access to level I and level II centers within 45 minutes. The percentages increased to 24%, 86%, and 95% when the time parameter was 60 minutes, the investigators reported (JAMA 2005:293;2626–33).

Beyond the Obvious

The study reveals much of “what we all knew intuitively,” said Jon R. Krohmer, M.D., medical director of Kent County EMS in Grand Rapids, Mich., and the ACEP liaison to the American College of Surgeons' Committee on Trauma.

It's significantly “innovative,” however, because the data sources are new and because investigators evaluated access in terms of population, as opposed to land area only. The researchers also measured access in terms of “prehospital time”—the time from receipt of an emergency call to hospital arrival—as opposed to distance or pure “transport time,” Dr. Krohmer said.

The investigators mainly used the January 2005 Trauma Center Inventory verified by the ACS Committee on Trauma, and the January 2005 version of the Atlas and Database of Air Medical Services.

“The study points out very graphically that there are areas that are potentially overserved, and areas that aren't served at all,” said Dr. Krohmer, an attending physician at Spectrum Health and medical director of Kent County EMS, both in Grand Rapids, Mich.

So, would a level I trauma center ever be built in Big Piney, Wyoming? “That's the million-dollar question,” he said. “And that's why this study should be the basis for future studies on quality of care and outcomes.

“We've asked, for instance, what is a minimal or acceptable patient volume to support a level I center? And right now, we don't have good answers,” Dr. Krohmer said.

Accessing Solutions

In their comments, the investigators question whether the access of some Americans to multiple trauma centers may be excessive, and whether “appropriate limits” on the number of centers could increase patient volumes and thus improve the quality of care—questions that both Dr. Krohmer and Dr. Larkin said are good ones.

The authors also emphasize the finding that 27% and 28% of U.S. residents had access—within 45 and 60 minutes, respectively—to level I and II centers by helicopter only.

“This, and the fact that base helipads are more moveable … makes them appealing as modifiable components of the trauma system,” wrote Charles C. Branas, Ph.D., an epidemiologist at the University of Pennsylvania, Philadelphia, and his associates.

National leadership on trauma care issues should also be better funded and more extensive, though “at this point, states need to get their systems (better) developed,” Dr. Branas told ACEP NEWS. States also need to make or strengthen arrangements for border crossings for day-to-day trauma care, he and his associates wrote.

Approximately 2%–3% of U.S. residents had access to level I and II trauma centers only via the centers and helicopters of neighboring states, the study showed. Most of the standardized interstate agreements for sharing resources, however, concern mass casualty incidents rather than day-to-day trauma care, the investigators said.

Dr. Larkin said he agrees that more “well-institutionalized” interstate arrangements are needed. He said he worries, on the other hand, that the potential of helicopters—which he said are now too often “big billboards for hospitals”—will be overstated and used as part of a cookie-cutter approach to solving access discrepancies.

He would rather see investigators and policymakers pair the new data on access with epidemiologic data—looking, for instance, at where motor vehicle crashes (the most common cause of trauma) occur most frequently.

“I hope people don't misread the data and assume it's the last word on trauma care,” said Dr. Larkin. “There is a whole host of other issues that need to be addressed.”

These include the issue of financing trauma care, a significant portion of which goes unpaid for, and issues of manpower and varying “densities” across the country of board-certified trauma surgeons and emergency physicians, he said.

Dr. Larkin emphasized that there's “a pretty big difference between level I and level II centers.” He advised paying more attention to access within 45 minutes than to access within the 60-minute time frame, since—as the investigators also point out—the so-called golden hour cutoff is supported by little scientific evidence and is probably too long.

Because the study excluded pediatric trauma centers and did not stratify access by age, the findings understate the access problems faced by the younger population, Dr. Larkin noted. “Trauma,” he said, “is the most common cause of death in the first four decades.”

Findings from a national study of access to trauma centers vividly illustrate what many have suspected—some Americans have access to large numbers of trauma centers, while others have access to none.

Now, say leaders in emergency medicine, it's time to collect even more data and look more earnestly at how trauma care can be improved—not only by modifying the often politically driven placement of centers and transport, but also by examining and acting on issues of quality of care, financing, and manpower.

“This is very much a tip-of-the-iceberg analysis. [Access to trauma centers] is a huge issue, and it's important to get [these data] out there,” said Gregory Luke Larkin, M.D., immediate past chair of the American College of Emergency Physicians' Trauma and Injury Prevention Committee. Hopefully, the analysis will generate momentum in looking at access and other related issues, he added.

“It should be just the beginning of a conversation about trauma care,” said Dr. Larkin, professor of surgery, emergency medicine, and public health at the University of Texas Southwestern Medical Center at Dallas. “And it should give permission for folks to talk about it at a national level,” as well as within states, he said.

The investigators of the cross-sectional study, published last month in the Journal of the American Medical Association, found that almost 70% of all U.S. residents had access to a level I or level II trauma center within 45 minutes, and that approximately 84% had access within 60 minutes.

While almost 43 million of these residents—most living in urban areas—had access within an hour to 20 or more level I or II centers, almost 47 million—most in rural areas—had no such access to any centers.

Only 8% of rural residents—compared with 73% of suburban populations and 89% of urban populations—had access to level I and level II centers within 45 minutes. The percentages increased to 24%, 86%, and 95% when the time parameter was 60 minutes, the investigators reported (JAMA 2005:293;2626–33).

Beyond the Obvious

The study reveals much of “what we all knew intuitively,” said Jon R. Krohmer, M.D., medical director of Kent County EMS in Grand Rapids, Mich., and the ACEP liaison to the American College of Surgeons' Committee on Trauma.

It's significantly “innovative,” however, because the data sources are new and because investigators evaluated access in terms of population, as opposed to land area only. The researchers also measured access in terms of “prehospital time”—the time from receipt of an emergency call to hospital arrival—as opposed to distance or pure “transport time,” Dr. Krohmer said.

The investigators mainly used the January 2005 Trauma Center Inventory verified by the ACS Committee on Trauma, and the January 2005 version of the Atlas and Database of Air Medical Services.

“The study points out very graphically that there are areas that are potentially overserved, and areas that aren't served at all,” said Dr. Krohmer, an attending physician at Spectrum Health and medical director of Kent County EMS, both in Grand Rapids, Mich.

So, would a level I trauma center ever be built in Big Piney, Wyoming? “That's the million-dollar question,” he said. “And that's why this study should be the basis for future studies on quality of care and outcomes.

“We've asked, for instance, what is a minimal or acceptable patient volume to support a level I center? And right now, we don't have good answers,” Dr. Krohmer said.

Accessing Solutions

In their comments, the investigators question whether the access of some Americans to multiple trauma centers may be excessive, and whether “appropriate limits” on the number of centers could increase patient volumes and thus improve the quality of care—questions that both Dr. Krohmer and Dr. Larkin said are good ones.

The authors also emphasize the finding that 27% and 28% of U.S. residents had access—within 45 and 60 minutes, respectively—to level I and II centers by helicopter only.

“This, and the fact that base helipads are more moveable … makes them appealing as modifiable components of the trauma system,” wrote Charles C. Branas, Ph.D., an epidemiologist at the University of Pennsylvania, Philadelphia, and his associates.

National leadership on trauma care issues should also be better funded and more extensive, though “at this point, states need to get their systems (better) developed,” Dr. Branas told ACEP NEWS. States also need to make or strengthen arrangements for border crossings for day-to-day trauma care, he and his associates wrote.

Approximately 2%–3% of U.S. residents had access to level I and II trauma centers only via the centers and helicopters of neighboring states, the study showed. Most of the standardized interstate agreements for sharing resources, however, concern mass casualty incidents rather than day-to-day trauma care, the investigators said.

Dr. Larkin said he agrees that more “well-institutionalized” interstate arrangements are needed. He said he worries, on the other hand, that the potential of helicopters—which he said are now too often “big billboards for hospitals”—will be overstated and used as part of a cookie-cutter approach to solving access discrepancies.

He would rather see investigators and policymakers pair the new data on access with epidemiologic data—looking, for instance, at where motor vehicle crashes (the most common cause of trauma) occur most frequently.

“I hope people don't misread the data and assume it's the last word on trauma care,” said Dr. Larkin. “There is a whole host of other issues that need to be addressed.”

These include the issue of financing trauma care, a significant portion of which goes unpaid for, and issues of manpower and varying “densities” across the country of board-certified trauma surgeons and emergency physicians, he said.

Dr. Larkin emphasized that there's “a pretty big difference between level I and level II centers.” He advised paying more attention to access within 45 minutes than to access within the 60-minute time frame, since—as the investigators also point out—the so-called golden hour cutoff is supported by little scientific evidence and is probably too long.

Because the study excluded pediatric trauma centers and did not stratify access by age, the findings understate the access problems faced by the younger population, Dr. Larkin noted. “Trauma,” he said, “is the most common cause of death in the first four decades.”

WASHINGTON — Specially designed physical education classes that increase levels of physical activity were better for overweight children than typical classes focusing on team-oriented sports and games, according to findings from a school-based study.

During the course of a school year, the children in the fitness-focused classes lost more body fat and had greater improvements in fasting insulin levels and cardiovascular fitness, Aaron L. Carrel, M.D., said at the annual meeting of the Pediatric Academic Societies.

“We need to partner with the schools” to improve the health of overweight children, said Dr. Carrel of the department of pediatrics at the University of Wisconsin, Madison.

Dr. Carrel and his associates worked with a school district outside of Madison to randomize 50 overweight, middle-school children to either standard physical education classes, which emphasize team sports and games, or to fitness-oriented gym classes. All classes were held three times a week for 42 minutes.

The fitness-oriented classes were smaller in size—approximately 15 students, compared with 30–35—and focused on the use of equipment, such as treadmills, and other fitness-oriented activities. “In the [standard] class, there was more standing around and choosing teams,” Dr. Carrel noted at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

All students had a body mass index above the 95th percentile for age. At the beginning and end of the school year, they underwent fasting evaluation of insulin and glucose and measurement of body composition by dual x-ray absorptiometry (DXA).

They also participated in maximal oxygen consumption (VO₂ max) treadmill testing that was progressive and staged. Every minute the treadmill got steeper “until the children couldn't exercise any longer,” he said.

At baseline, there were no significant differences between the two groups in any of these measures. But after the 9-month school year was up, the children in the specially designed classes had a greater loss of body fat (4% vs. 2%), a greater increase in cardiovascular fitness (an increase in VO₂ max of nearly 3 mL/kg per minute vs. less than 1 mL/kg per minute), and greater improvement in fasting insulin (−5 μIU/mL vs. +3 μIU/mL).

Other research conducted has shown that fitness has a greater correlation with insulin than body fat, Dr. Carrel noted.

WASHINGTON — Specially designed physical education classes that increase levels of physical activity were better for overweight children than typical classes focusing on team-oriented sports and games, according to findings from a school-based study.

During the course of a school year, the children in the fitness-focused classes lost more body fat and had greater improvements in fasting insulin levels and cardiovascular fitness, Aaron L. Carrel, M.D., said at the annual meeting of the Pediatric Academic Societies.

“We need to partner with the schools” to improve the health of overweight children, said Dr. Carrel of the department of pediatrics at the University of Wisconsin, Madison.

Dr. Carrel and his associates worked with a school district outside of Madison to randomize 50 overweight, middle-school children to either standard physical education classes, which emphasize team sports and games, or to fitness-oriented gym classes. All classes were held three times a week for 42 minutes.

The fitness-oriented classes were smaller in size—approximately 15 students, compared with 30–35—and focused on the use of equipment, such as treadmills, and other fitness-oriented activities. “In the [standard] class, there was more standing around and choosing teams,” Dr. Carrel noted at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

All students had a body mass index above the 95th percentile for age. At the beginning and end of the school year, they underwent fasting evaluation of insulin and glucose and measurement of body composition by dual x-ray absorptiometry (DXA).

They also participated in maximal oxygen consumption (VO₂ max) treadmill testing that was progressive and staged. Every minute the treadmill got steeper “until the children couldn't exercise any longer,” he said.

At baseline, there were no significant differences between the two groups in any of these measures. But after the 9-month school year was up, the children in the specially designed classes had a greater loss of body fat (4% vs. 2%), a greater increase in cardiovascular fitness (an increase in VO₂ max of nearly 3 mL/kg per minute vs. less than 1 mL/kg per minute), and greater improvement in fasting insulin (−5 μIU/mL vs. +3 μIU/mL).

Other research conducted has shown that fitness has a greater correlation with insulin than body fat, Dr. Carrel noted.

WASHINGTON — Specially designed physical education classes that increase levels of physical activity were better for overweight children than typical classes focusing on team-oriented sports and games, according to findings from a school-based study.

During the course of a school year, the children in the fitness-focused classes lost more body fat and had greater improvements in fasting insulin levels and cardiovascular fitness, Aaron L. Carrel, M.D., said at the annual meeting of the Pediatric Academic Societies.

“We need to partner with the schools” to improve the health of overweight children, said Dr. Carrel of the department of pediatrics at the University of Wisconsin, Madison.

Dr. Carrel and his associates worked with a school district outside of Madison to randomize 50 overweight, middle-school children to either standard physical education classes, which emphasize team sports and games, or to fitness-oriented gym classes. All classes were held three times a week for 42 minutes.

The fitness-oriented classes were smaller in size—approximately 15 students, compared with 30–35—and focused on the use of equipment, such as treadmills, and other fitness-oriented activities. “In the [standard] class, there was more standing around and choosing teams,” Dr. Carrel noted at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

All students had a body mass index above the 95th percentile for age. At the beginning and end of the school year, they underwent fasting evaluation of insulin and glucose and measurement of body composition by dual x-ray absorptiometry (DXA).

They also participated in maximal oxygen consumption (VO₂ max) treadmill testing that was progressive and staged. Every minute the treadmill got steeper “until the children couldn't exercise any longer,” he said.

At baseline, there were no significant differences between the two groups in any of these measures. But after the 9-month school year was up, the children in the specially designed classes had a greater loss of body fat (4% vs. 2%), a greater increase in cardiovascular fitness (an increase in VO₂ max of nearly 3 mL/kg per minute vs. less than 1 mL/kg per minute), and greater improvement in fasting insulin (−5 μIU/mL vs. +3 μIU/mL).

Other research conducted has shown that fitness has a greater correlation with insulin than body fat, Dr. Carrel noted.

Contrary to popular opinion, posttraumatic stress disorder and depression in war survivors appear to develop independently of a perceived lack of redress for trauma, according to a study conducted in three former Yugoslav republics.

Impunity for those responsible for trauma is widely believed to aggravate psychological problems in survivors of war.

But a cross-sectional survey of more than 1,300 war survivors in four areas of the former Yugoslavia suggests that a general fear-induced helplessness—rather than emotional responses to impunity specifically—is the most important mediating factor in PTSD and depression, said Metin Basoglu, M.D., of the Institute of Psychiatry at King's College in London, and associates (JAMA 2005;294:580–90).

Survivors had stronger emotional responses to impunity than did individuals who did not directly experience the trauma of war (the controls)—in addition to higher rates of PTSD and depression—but they also had greater fear and loss of control over life. It was these latter factors that played the biggest role, they said.

The findings might have “important implications for reconciliation efforts in postwar countries and effective interventions for traumatized war survivors,” the investigators said.

Contrary to popular opinion, posttraumatic stress disorder and depression in war survivors appear to develop independently of a perceived lack of redress for trauma, according to a study conducted in three former Yugoslav republics.

Impunity for those responsible for trauma is widely believed to aggravate psychological problems in survivors of war.

But a cross-sectional survey of more than 1,300 war survivors in four areas of the former Yugoslavia suggests that a general fear-induced helplessness—rather than emotional responses to impunity specifically—is the most important mediating factor in PTSD and depression, said Metin Basoglu, M.D., of the Institute of Psychiatry at King's College in London, and associates (JAMA 2005;294:580–90).

Survivors had stronger emotional responses to impunity than did individuals who did not directly experience the trauma of war (the controls)—in addition to higher rates of PTSD and depression—but they also had greater fear and loss of control over life. It was these latter factors that played the biggest role, they said.

The findings might have “important implications for reconciliation efforts in postwar countries and effective interventions for traumatized war survivors,” the investigators said.

Contrary to popular opinion, posttraumatic stress disorder and depression in war survivors appear to develop independently of a perceived lack of redress for trauma, according to a study conducted in three former Yugoslav republics.

Impunity for those responsible for trauma is widely believed to aggravate psychological problems in survivors of war.

But a cross-sectional survey of more than 1,300 war survivors in four areas of the former Yugoslavia suggests that a general fear-induced helplessness—rather than emotional responses to impunity specifically—is the most important mediating factor in PTSD and depression, said Metin Basoglu, M.D., of the Institute of Psychiatry at King's College in London, and associates (JAMA 2005;294:580–90).

Survivors had stronger emotional responses to impunity than did individuals who did not directly experience the trauma of war (the controls)—in addition to higher rates of PTSD and depression—but they also had greater fear and loss of control over life. It was these latter factors that played the biggest role, they said.

The findings might have “important implications for reconciliation efforts in postwar countries and effective interventions for traumatized war survivors,” the investigators said.