Bruce Jancin

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela reported having no financial conflicts.

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela reported having no financial conflicts.

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela reported having no financial conflicts.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

In a study of 1,228 nonfatal acute MIs, only 5% appeared to be triggered by exercise. And in a classic study from the 1980s, when the management of patients with acute MI was much less sophisticated and effective than today, data obtained from 167 randomly chosen cardiac rehab programs demonstrated that there was one acute MI per 300,000 supervised exercise hours, one cardiac arrest per 112,000 exercise hours, and one death per 800,000 exercise hours (JAMA 1986;256:1160-3).

The mechanisms through which depression and other forms of psychologic stress boost the risk of secondary cardiac events are thought to include increased platelet reactivity, systemic inflammation, sympathetic activation of the autonomic nervous system, endothelial dysfunction, and increased circulating catecholamines.

Robert M. Carney, Ph.D., pointed out that depression is not only the number-two cause of early death and disability in industrialized nations, but the prevalence of major depression in the months following an acute coronary syndrome has been pegged at 12%-23% in various studies, with another 15%-27% of ACS patients having minor depression.

Thus, close to half of all ACS patients experience significant depressive symptoms (Am. J. Med. 2008;121:S20-7), according to Dr. Carney, professor of psychiatry at Washington University in St. Louis.

What’s more, there is persuasive evidence to show that depression in patients who have experienced an acute coronary syndrome is associated with increased mortality. Dr. Carney cited a recent meta-analysis covering the last 25 years of research on depression and heart disease, which concluded that post-MI depression was independently associated with a 2.7-fold increased likelihood of cardiac mortality and a 1.6-fold increase in cardiac morbidity (Gen. Hosp. Psychiatry 2011;33:203-16).

Although several randomized trials have demonstrated that exercise can reduce depression in CHD patients, there is as yet no randomized trial evidence demonstrating that treating depression actually improves survival in patients with heart disease.

Dr. Carney calls this "the Holy Grail of behavioral psychology." He believes this goal has proved elusive to date because depression is often a remitting and relapsing disorder, and the standard antidepressant therapies, whether pharmacologic or psychotherapies, are "fairly modest" in their effects. The randomized trial data suggest exercise training is in the same efficacy ballpark.

"Exercise appears to be doing about as well as antidepressant drugs or some of the psychotherapies, but it’s not doing a whole lot better," Dr. Carney asserted. "It seems clear to me that monotherapy for depression is often insufficient, both in psychiatric patients and in CHD."

There is, however, some intriguing evidence to suggest that exercise training might be particularly effective in patients whose depression doesn’t respond to traditional antidepressant therapies, the psychologist said. For example, Scottish investigators took 86 primary care patients with major depressive disorder unresponsive to at least 6 weeks of an adequately dosed antidepressant drug and randomized them to a combined endurance and weight-training exercise program or a group health education control group. The two groups met twice weekly for 10 weeks, at which point at least a 30% improvement in HAM-D scores had occurred in 55% of the exercise group and in 33% of controls (Br. J. Psychiatry 2002;180:411-5).

For this reason, Dr. Carney proposed that the next large, multicenter, NIH-sponsored clinical trial testing the hypothesis that treating depression in CHD patients improves survival should include an exercise training arm. But not exercise as monotherapy; instead, exercise should be employed as part of a combination treatment or augmentation strategy, or perhaps in a sequential stepped-care regimen for initial nonresponders.

The approach he advocates is modeled on the stepped-care approach that proved highly effective in the landmark randomized, multicenter Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial. In step 1 of STAR*D, the remission rate with antidepressant monotherapy was 33%; in step 2, with the addition of a second antidepressant or a switch to a different one, the cumulative remission rate climbed to 53% (Am. J. Psychiatry 2006;163:1905-17).

Exercise training as part of combination antidepressant therapy in patients with CHD is attractive for several reasons. Not only may it be more effective than monotherapy, but it confers numerous cardiovascular and general health benefits. And it avoids drug-drug interactions.

"I think that’s a really important consideration in cardiac patients, who often are on 8, 10, 12 different drugs. And SSRIs in particular seem to interact with other drugs," Dr. Carney said.

Dr. Lavie and Dr. Carney reported having no financial conflicts.

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

In a study of 1,228 nonfatal acute MIs, only 5% appeared to be triggered by exercise. And in a classic study from the 1980s, when the management of patients with acute MI was much less sophisticated and effective than today, data obtained from 167 randomly chosen cardiac rehab programs demonstrated that there was one acute MI per 300,000 supervised exercise hours, one cardiac arrest per 112,000 exercise hours, and one death per 800,000 exercise hours (JAMA 1986;256:1160-3).

The mechanisms through which depression and other forms of psychologic stress boost the risk of secondary cardiac events are thought to include increased platelet reactivity, systemic inflammation, sympathetic activation of the autonomic nervous system, endothelial dysfunction, and increased circulating catecholamines.

Robert M. Carney, Ph.D., pointed out that depression is not only the number-two cause of early death and disability in industrialized nations, but the prevalence of major depression in the months following an acute coronary syndrome has been pegged at 12%-23% in various studies, with another 15%-27% of ACS patients having minor depression.

Thus, close to half of all ACS patients experience significant depressive symptoms (Am. J. Med. 2008;121:S20-7), according to Dr. Carney, professor of psychiatry at Washington University in St. Louis.

What’s more, there is persuasive evidence to show that depression in patients who have experienced an acute coronary syndrome is associated with increased mortality. Dr. Carney cited a recent meta-analysis covering the last 25 years of research on depression and heart disease, which concluded that post-MI depression was independently associated with a 2.7-fold increased likelihood of cardiac mortality and a 1.6-fold increase in cardiac morbidity (Gen. Hosp. Psychiatry 2011;33:203-16).

Although several randomized trials have demonstrated that exercise can reduce depression in CHD patients, there is as yet no randomized trial evidence demonstrating that treating depression actually improves survival in patients with heart disease.

Dr. Carney calls this "the Holy Grail of behavioral psychology." He believes this goal has proved elusive to date because depression is often a remitting and relapsing disorder, and the standard antidepressant therapies, whether pharmacologic or psychotherapies, are "fairly modest" in their effects. The randomized trial data suggest exercise training is in the same efficacy ballpark.

"Exercise appears to be doing about as well as antidepressant drugs or some of the psychotherapies, but it’s not doing a whole lot better," Dr. Carney asserted. "It seems clear to me that monotherapy for depression is often insufficient, both in psychiatric patients and in CHD."

There is, however, some intriguing evidence to suggest that exercise training might be particularly effective in patients whose depression doesn’t respond to traditional antidepressant therapies, the psychologist said. For example, Scottish investigators took 86 primary care patients with major depressive disorder unresponsive to at least 6 weeks of an adequately dosed antidepressant drug and randomized them to a combined endurance and weight-training exercise program or a group health education control group. The two groups met twice weekly for 10 weeks, at which point at least a 30% improvement in HAM-D scores had occurred in 55% of the exercise group and in 33% of controls (Br. J. Psychiatry 2002;180:411-5).

For this reason, Dr. Carney proposed that the next large, multicenter, NIH-sponsored clinical trial testing the hypothesis that treating depression in CHD patients improves survival should include an exercise training arm. But not exercise as monotherapy; instead, exercise should be employed as part of a combination treatment or augmentation strategy, or perhaps in a sequential stepped-care regimen for initial nonresponders.

The approach he advocates is modeled on the stepped-care approach that proved highly effective in the landmark randomized, multicenter Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial. In step 1 of STAR*D, the remission rate with antidepressant monotherapy was 33%; in step 2, with the addition of a second antidepressant or a switch to a different one, the cumulative remission rate climbed to 53% (Am. J. Psychiatry 2006;163:1905-17).

Exercise training as part of combination antidepressant therapy in patients with CHD is attractive for several reasons. Not only may it be more effective than monotherapy, but it confers numerous cardiovascular and general health benefits. And it avoids drug-drug interactions.

"I think that’s a really important consideration in cardiac patients, who often are on 8, 10, 12 different drugs. And SSRIs in particular seem to interact with other drugs," Dr. Carney said.

Dr. Lavie and Dr. Carney reported having no financial conflicts.

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

In a study of 1,228 nonfatal acute MIs, only 5% appeared to be triggered by exercise. And in a classic study from the 1980s, when the management of patients with acute MI was much less sophisticated and effective than today, data obtained from 167 randomly chosen cardiac rehab programs demonstrated that there was one acute MI per 300,000 supervised exercise hours, one cardiac arrest per 112,000 exercise hours, and one death per 800,000 exercise hours (JAMA 1986;256:1160-3).

The mechanisms through which depression and other forms of psychologic stress boost the risk of secondary cardiac events are thought to include increased platelet reactivity, systemic inflammation, sympathetic activation of the autonomic nervous system, endothelial dysfunction, and increased circulating catecholamines.

Robert M. Carney, Ph.D., pointed out that depression is not only the number-two cause of early death and disability in industrialized nations, but the prevalence of major depression in the months following an acute coronary syndrome has been pegged at 12%-23% in various studies, with another 15%-27% of ACS patients having minor depression.

Thus, close to half of all ACS patients experience significant depressive symptoms (Am. J. Med. 2008;121:S20-7), according to Dr. Carney, professor of psychiatry at Washington University in St. Louis.

What’s more, there is persuasive evidence to show that depression in patients who have experienced an acute coronary syndrome is associated with increased mortality. Dr. Carney cited a recent meta-analysis covering the last 25 years of research on depression and heart disease, which concluded that post-MI depression was independently associated with a 2.7-fold increased likelihood of cardiac mortality and a 1.6-fold increase in cardiac morbidity (Gen. Hosp. Psychiatry 2011;33:203-16).

Although several randomized trials have demonstrated that exercise can reduce depression in CHD patients, there is as yet no randomized trial evidence demonstrating that treating depression actually improves survival in patients with heart disease.

Dr. Carney calls this "the Holy Grail of behavioral psychology." He believes this goal has proved elusive to date because depression is often a remitting and relapsing disorder, and the standard antidepressant therapies, whether pharmacologic or psychotherapies, are "fairly modest" in their effects. The randomized trial data suggest exercise training is in the same efficacy ballpark.

"Exercise appears to be doing about as well as antidepressant drugs or some of the psychotherapies, but it’s not doing a whole lot better," Dr. Carney asserted. "It seems clear to me that monotherapy for depression is often insufficient, both in psychiatric patients and in CHD."

There is, however, some intriguing evidence to suggest that exercise training might be particularly effective in patients whose depression doesn’t respond to traditional antidepressant therapies, the psychologist said. For example, Scottish investigators took 86 primary care patients with major depressive disorder unresponsive to at least 6 weeks of an adequately dosed antidepressant drug and randomized them to a combined endurance and weight-training exercise program or a group health education control group. The two groups met twice weekly for 10 weeks, at which point at least a 30% improvement in HAM-D scores had occurred in 55% of the exercise group and in 33% of controls (Br. J. Psychiatry 2002;180:411-5).

For this reason, Dr. Carney proposed that the next large, multicenter, NIH-sponsored clinical trial testing the hypothesis that treating depression in CHD patients improves survival should include an exercise training arm. But not exercise as monotherapy; instead, exercise should be employed as part of a combination treatment or augmentation strategy, or perhaps in a sequential stepped-care regimen for initial nonresponders.

The approach he advocates is modeled on the stepped-care approach that proved highly effective in the landmark randomized, multicenter Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial. In step 1 of STAR*D, the remission rate with antidepressant monotherapy was 33%; in step 2, with the addition of a second antidepressant or a switch to a different one, the cumulative remission rate climbed to 53% (Am. J. Psychiatry 2006;163:1905-17).

Exercise training as part of combination antidepressant therapy in patients with CHD is attractive for several reasons. Not only may it be more effective than monotherapy, but it confers numerous cardiovascular and general health benefits. And it avoids drug-drug interactions.

"I think that’s a really important consideration in cardiac patients, who often are on 8, 10, 12 different drugs. And SSRIs in particular seem to interact with other drugs," Dr. Carney said.

Dr. Lavie and Dr. Carney reported having no financial conflicts.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – Consistent daily use of full-dose NSAIDs significantly slows radiographic spinal progression in ankylosing spondylitis patients but only in the subgroup with risk factors for progression – namely, syndesmophytes and elevated C-reactive protein or erythrocyte sedimentation rate.

Ankylosing spondylitis (AS) patients without these risk factors have such a low rate of radiographic spinal progression over 2 years of follow-up that their risk is unaffected by how consistently they use NSAIDs, Dr. Denis Poddubnyy reported at the annual European Congress of Rheumatology.

These conclusions are based on two studies presented at the meeting: one by Dr. Poddubnyy involving participants in a prospective registry known as the German Spondyloarthritis Inception Cohort, and the other a new post hoc analysis of data from the first, and to date the only, randomized controlled trial of the impact of consistently high versus as-needed use of NSAIDs on radiographic spinal progression in patients with AS.

"I think these data might change future treatment guidelines as we move along the way to more individualized treatment for patients with ankylosing spondylitis. Symptomatic patients who require NSAIDs would benefit most from the medication if they also have risk factors associated with radiographic progression," said Dr. Poddubnyy of Charité Hospital in Berlin.

He presented a study of 164 German registry participants, all with definite early axial spondyloarthritis. Eighty-eight patients met diagnostic criteria for axial AS, and the other 76 had nonradiographic axial spondyloarthritis. They were selected from the registry because they all had 2 years of serial spinal x-rays and detailed information on their NSAID use during that period. Axial spinal x-rays were independently assessed by two blinded readers using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). NSAID intake was rated using a scoring system developed by the Assessment of Spondylarthritis International Society (Ann. Rheum. Dis. 2011;70:249-51).

Sixty-four AS patients were categorized as having low NSAID intake, defined as less than 50% of daily full-dose use. These patients took NSAIDs on an as-needed basis. They had a substantial rate of radiographic progression of their spinal disease: a mean 0.96-point increase in mSASSS over the course of 2 years from a baseline score of about 6. In contrast, patients with high NSAID intake – that is, at least 50% of full-dose therapy 7 days a week – had virtually no radiographic progression, with a mean 0.02-point increase. Consistent use of full-dose NSAIDs had a beneficial structure-modifying effect on new bone formation, the rheumatologist observed.

A multivariate logistic regression analysis identified two independent risk factors for substantial radiographic spinal progression: the presence of syndesmophytes on the baseline spinal x-ray and a consistently elevated C-reactive protein (CRP) level. Baseline syndesmophytes were by far the most potent risk factor, with an associated 6.8-fold increased risk. AS patients with one or both of these risk factors and low NSAID intake averaged a 4.36-point increase in mSASSS scores over 2 years, while high NSAID users with risk factors averaged a nonsignificant 0.14-point increase.

"Remarkably, in patients without risk factors for progression we saw nearly no progression, and no difference between high and low NSAID intake," according to Dr. Poddubnyy.

In response to an audience question, he estimated that about 30% of AS patients have risk factors for radiographic spinal progression.

In the 76 registry patients with nonradiographic axial spondyloarthritis, the level of NSAID use made no difference in terms of the rate of change in mSASSS scores. "At this stage, radiographic progression in these patients is probably due to forces other than new bone formation," he explained.

Dr. Poddubnyy noted that while this was not a randomized trial, the registry findings were confirmed in another study presented during the congress. This was a Dutch post hoc secondary analysis of data from the only randomized prospective clinical trial to date demonstrating that continuous NSAID intake over a 2-year period was associated with significantly less radiographic spinal progression than as-needed use (Arthritis Rheum. 2005;52:1756-65).

The new post hoc analysis of 150 AS patients randomized to continuous or as-needed celecoxib showed that retardation of radiographic spinal progression through high intake of NSAIDs was essentially confined to patients with either of two baseline risk factors for radiographic progression: a consistently elevated CRP or an elevated erythrocyte sedimentation rate (ESR).

The Dutch investigators found that patients with a high baseline CRP had a 13% rate of substantial radiographic disease progression during 2 years if they used celecoxib continuously compared with a 38% rate with as-needed use. Those with an elevated ESR had a 22% risk of substantial progression if they used the NSAID continuously but a 49% risk if they took celecoxib on an as-needed basis.

These two studies, Dr. Poddubnyy continued, point the way toward maximizing the risk/benefit ratio of NSAID therapy in patients with AS.

The German registry study was funded by the German Rheumatism Research Center of Berlin. Dr. Poddubnyy reported having no financial conflicts.

BERLIN – Consistent daily use of full-dose NSAIDs significantly slows radiographic spinal progression in ankylosing spondylitis patients but only in the subgroup with risk factors for progression – namely, syndesmophytes and elevated C-reactive protein or erythrocyte sedimentation rate.

Ankylosing spondylitis (AS) patients without these risk factors have such a low rate of radiographic spinal progression over 2 years of follow-up that their risk is unaffected by how consistently they use NSAIDs, Dr. Denis Poddubnyy reported at the annual European Congress of Rheumatology.

These conclusions are based on two studies presented at the meeting: one by Dr. Poddubnyy involving participants in a prospective registry known as the German Spondyloarthritis Inception Cohort, and the other a new post hoc analysis of data from the first, and to date the only, randomized controlled trial of the impact of consistently high versus as-needed use of NSAIDs on radiographic spinal progression in patients with AS.

"I think these data might change future treatment guidelines as we move along the way to more individualized treatment for patients with ankylosing spondylitis. Symptomatic patients who require NSAIDs would benefit most from the medication if they also have risk factors associated with radiographic progression," said Dr. Poddubnyy of Charité Hospital in Berlin.

He presented a study of 164 German registry participants, all with definite early axial spondyloarthritis. Eighty-eight patients met diagnostic criteria for axial AS, and the other 76 had nonradiographic axial spondyloarthritis. They were selected from the registry because they all had 2 years of serial spinal x-rays and detailed information on their NSAID use during that period. Axial spinal x-rays were independently assessed by two blinded readers using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). NSAID intake was rated using a scoring system developed by the Assessment of Spondylarthritis International Society (Ann. Rheum. Dis. 2011;70:249-51).

Sixty-four AS patients were categorized as having low NSAID intake, defined as less than 50% of daily full-dose use. These patients took NSAIDs on an as-needed basis. They had a substantial rate of radiographic progression of their spinal disease: a mean 0.96-point increase in mSASSS over the course of 2 years from a baseline score of about 6. In contrast, patients with high NSAID intake – that is, at least 50% of full-dose therapy 7 days a week – had virtually no radiographic progression, with a mean 0.02-point increase. Consistent use of full-dose NSAIDs had a beneficial structure-modifying effect on new bone formation, the rheumatologist observed.

A multivariate logistic regression analysis identified two independent risk factors for substantial radiographic spinal progression: the presence of syndesmophytes on the baseline spinal x-ray and a consistently elevated C-reactive protein (CRP) level. Baseline syndesmophytes were by far the most potent risk factor, with an associated 6.8-fold increased risk. AS patients with one or both of these risk factors and low NSAID intake averaged a 4.36-point increase in mSASSS scores over 2 years, while high NSAID users with risk factors averaged a nonsignificant 0.14-point increase.

"Remarkably, in patients without risk factors for progression we saw nearly no progression, and no difference between high and low NSAID intake," according to Dr. Poddubnyy.

In response to an audience question, he estimated that about 30% of AS patients have risk factors for radiographic spinal progression.

In the 76 registry patients with nonradiographic axial spondyloarthritis, the level of NSAID use made no difference in terms of the rate of change in mSASSS scores. "At this stage, radiographic progression in these patients is probably due to forces other than new bone formation," he explained.

Dr. Poddubnyy noted that while this was not a randomized trial, the registry findings were confirmed in another study presented during the congress. This was a Dutch post hoc secondary analysis of data from the only randomized prospective clinical trial to date demonstrating that continuous NSAID intake over a 2-year period was associated with significantly less radiographic spinal progression than as-needed use (Arthritis Rheum. 2005;52:1756-65).

The new post hoc analysis of 150 AS patients randomized to continuous or as-needed celecoxib showed that retardation of radiographic spinal progression through high intake of NSAIDs was essentially confined to patients with either of two baseline risk factors for radiographic progression: a consistently elevated CRP or an elevated erythrocyte sedimentation rate (ESR).

The Dutch investigators found that patients with a high baseline CRP had a 13% rate of substantial radiographic disease progression during 2 years if they used celecoxib continuously compared with a 38% rate with as-needed use. Those with an elevated ESR had a 22% risk of substantial progression if they used the NSAID continuously but a 49% risk if they took celecoxib on an as-needed basis.

These two studies, Dr. Poddubnyy continued, point the way toward maximizing the risk/benefit ratio of NSAID therapy in patients with AS.

The German registry study was funded by the German Rheumatism Research Center of Berlin. Dr. Poddubnyy reported having no financial conflicts.

BERLIN – Consistent daily use of full-dose NSAIDs significantly slows radiographic spinal progression in ankylosing spondylitis patients but only in the subgroup with risk factors for progression – namely, syndesmophytes and elevated C-reactive protein or erythrocyte sedimentation rate.

Ankylosing spondylitis (AS) patients without these risk factors have such a low rate of radiographic spinal progression over 2 years of follow-up that their risk is unaffected by how consistently they use NSAIDs, Dr. Denis Poddubnyy reported at the annual European Congress of Rheumatology.

These conclusions are based on two studies presented at the meeting: one by Dr. Poddubnyy involving participants in a prospective registry known as the German Spondyloarthritis Inception Cohort, and the other a new post hoc analysis of data from the first, and to date the only, randomized controlled trial of the impact of consistently high versus as-needed use of NSAIDs on radiographic spinal progression in patients with AS.

"I think these data might change future treatment guidelines as we move along the way to more individualized treatment for patients with ankylosing spondylitis. Symptomatic patients who require NSAIDs would benefit most from the medication if they also have risk factors associated with radiographic progression," said Dr. Poddubnyy of Charité Hospital in Berlin.

He presented a study of 164 German registry participants, all with definite early axial spondyloarthritis. Eighty-eight patients met diagnostic criteria for axial AS, and the other 76 had nonradiographic axial spondyloarthritis. They were selected from the registry because they all had 2 years of serial spinal x-rays and detailed information on their NSAID use during that period. Axial spinal x-rays were independently assessed by two blinded readers using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). NSAID intake was rated using a scoring system developed by the Assessment of Spondylarthritis International Society (Ann. Rheum. Dis. 2011;70:249-51).

Sixty-four AS patients were categorized as having low NSAID intake, defined as less than 50% of daily full-dose use. These patients took NSAIDs on an as-needed basis. They had a substantial rate of radiographic progression of their spinal disease: a mean 0.96-point increase in mSASSS over the course of 2 years from a baseline score of about 6. In contrast, patients with high NSAID intake – that is, at least 50% of full-dose therapy 7 days a week – had virtually no radiographic progression, with a mean 0.02-point increase. Consistent use of full-dose NSAIDs had a beneficial structure-modifying effect on new bone formation, the rheumatologist observed.

A multivariate logistic regression analysis identified two independent risk factors for substantial radiographic spinal progression: the presence of syndesmophytes on the baseline spinal x-ray and a consistently elevated C-reactive protein (CRP) level. Baseline syndesmophytes were by far the most potent risk factor, with an associated 6.8-fold increased risk. AS patients with one or both of these risk factors and low NSAID intake averaged a 4.36-point increase in mSASSS scores over 2 years, while high NSAID users with risk factors averaged a nonsignificant 0.14-point increase.

"Remarkably, in patients without risk factors for progression we saw nearly no progression, and no difference between high and low NSAID intake," according to Dr. Poddubnyy.

In response to an audience question, he estimated that about 30% of AS patients have risk factors for radiographic spinal progression.

In the 76 registry patients with nonradiographic axial spondyloarthritis, the level of NSAID use made no difference in terms of the rate of change in mSASSS scores. "At this stage, radiographic progression in these patients is probably due to forces other than new bone formation," he explained.

Dr. Poddubnyy noted that while this was not a randomized trial, the registry findings were confirmed in another study presented during the congress. This was a Dutch post hoc secondary analysis of data from the only randomized prospective clinical trial to date demonstrating that continuous NSAID intake over a 2-year period was associated with significantly less radiographic spinal progression than as-needed use (Arthritis Rheum. 2005;52:1756-65).

The new post hoc analysis of 150 AS patients randomized to continuous or as-needed celecoxib showed that retardation of radiographic spinal progression through high intake of NSAIDs was essentially confined to patients with either of two baseline risk factors for radiographic progression: a consistently elevated CRP or an elevated erythrocyte sedimentation rate (ESR).

The Dutch investigators found that patients with a high baseline CRP had a 13% rate of substantial radiographic disease progression during 2 years if they used celecoxib continuously compared with a 38% rate with as-needed use. Those with an elevated ESR had a 22% risk of substantial progression if they used the NSAID continuously but a 49% risk if they took celecoxib on an as-needed basis.

These two studies, Dr. Poddubnyy continued, point the way toward maximizing the risk/benefit ratio of NSAID therapy in patients with AS.

The German registry study was funded by the German Rheumatism Research Center of Berlin. Dr. Poddubnyy reported having no financial conflicts.

RALEIGH, N.C. - Topical clindamycin phosphate 1.2%/tretinoin 0.025% gel was found to be significantly less irritating than benzoyl peroxide 2.5%/adapalene 0.1% gel was during the first 3 weeks of acne therapy, according to a double-blind, randomized, split-face comparative trial.

However, it should be noted that at all times, study participants scored their irritation as moderate or less with both medications. “Both products are pretty well tolerated. Nevertheless, looking at patient outcomes, clindamycin/tretinoin [Ziana]does seem to be less irritating than benzoyl peroxide/adapalene [Epiduo], which could be of clinical significance because it might [affect] patient compliance,” noted Dr. Renato Goreshi of the department of dermatology at the Oregon Health and Science University, Portland.

He presented a double-blind study involving 24 patients with mild to moderate facial acne at the annual meeting of the Society for Investigative Dermatology. All were white, and most were in their mid-20s.

Participants applied clindamycin/tretinoin to one side of their face and benzoyl peroxide/adapalene to the other side once daily for 3 weeks. They kept a daily record scoring burning/stinging and itching on a 0-3 scale. In addition, investigators measured transepidermal water loss and conducted Investigator’s Global Assessments of dryness/scaling and erythema at baseline and weekly thereafter.

The primary study outcome was transepidermal water loss, a reliable and validated measure of epidermal barrier disruption. Transepidermal water loss was significantly greater at weeks 1, 2, and 3 on the benzoyl peroxide/adapalene–treated side of the face.

The benzoyl peroxide/adapalene–treated side also scored threefold higher on the patients’ self-assessed rating of burning/stinging, and twice as high on itching.

“This isn’t entirely surprising, since in studies in atopic dermatitis we also see that there’s a correlation between higher transepidermal water-loss scores and increased pruritus, which is what we saw here,” Dr. Goreshi said.

The difference in composite irritancy scores was larger in the first half of the study than in the second half, when scores headed toward convergence.

Investigators found no significant difference between the two products in erythema or dryness/scaling.

There was also no significant difference between the two topical agents in terms of reduction of acne lesion counts. However, one wouldn’t expect to see significant differences during this short of a study, which was designed to look at irritancy, not efficacy, Dr. Goreshi noted.

The study was funded by Medicis, which markets Ziana.

RALEIGH, N.C. - Topical clindamycin phosphate 1.2%/tretinoin 0.025% gel was found to be significantly less irritating than benzoyl peroxide 2.5%/adapalene 0.1% gel was during the first 3 weeks of acne therapy, according to a double-blind, randomized, split-face comparative trial.

However, it should be noted that at all times, study participants scored their irritation as moderate or less with both medications. “Both products are pretty well tolerated. Nevertheless, looking at patient outcomes, clindamycin/tretinoin [Ziana]does seem to be less irritating than benzoyl peroxide/adapalene [Epiduo], which could be of clinical significance because it might [affect] patient compliance,” noted Dr. Renato Goreshi of the department of dermatology at the Oregon Health and Science University, Portland.

He presented a double-blind study involving 24 patients with mild to moderate facial acne at the annual meeting of the Society for Investigative Dermatology. All were white, and most were in their mid-20s.

Participants applied clindamycin/tretinoin to one side of their face and benzoyl peroxide/adapalene to the other side once daily for 3 weeks. They kept a daily record scoring burning/stinging and itching on a 0-3 scale. In addition, investigators measured transepidermal water loss and conducted Investigator’s Global Assessments of dryness/scaling and erythema at baseline and weekly thereafter.

The primary study outcome was transepidermal water loss, a reliable and validated measure of epidermal barrier disruption. Transepidermal water loss was significantly greater at weeks 1, 2, and 3 on the benzoyl peroxide/adapalene–treated side of the face.

The benzoyl peroxide/adapalene–treated side also scored threefold higher on the patients’ self-assessed rating of burning/stinging, and twice as high on itching.

“This isn’t entirely surprising, since in studies in atopic dermatitis we also see that there’s a correlation between higher transepidermal water-loss scores and increased pruritus, which is what we saw here,” Dr. Goreshi said.

The difference in composite irritancy scores was larger in the first half of the study than in the second half, when scores headed toward convergence.

Investigators found no significant difference between the two products in erythema or dryness/scaling.

There was also no significant difference between the two topical agents in terms of reduction of acne lesion counts. However, one wouldn’t expect to see significant differences during this short of a study, which was designed to look at irritancy, not efficacy, Dr. Goreshi noted.

The study was funded by Medicis, which markets Ziana.

RALEIGH, N.C. - Topical clindamycin phosphate 1.2%/tretinoin 0.025% gel was found to be significantly less irritating than benzoyl peroxide 2.5%/adapalene 0.1% gel was during the first 3 weeks of acne therapy, according to a double-blind, randomized, split-face comparative trial.

However, it should be noted that at all times, study participants scored their irritation as moderate or less with both medications. “Both products are pretty well tolerated. Nevertheless, looking at patient outcomes, clindamycin/tretinoin [Ziana]does seem to be less irritating than benzoyl peroxide/adapalene [Epiduo], which could be of clinical significance because it might [affect] patient compliance,” noted Dr. Renato Goreshi of the department of dermatology at the Oregon Health and Science University, Portland.

He presented a double-blind study involving 24 patients with mild to moderate facial acne at the annual meeting of the Society for Investigative Dermatology. All were white, and most were in their mid-20s.

Participants applied clindamycin/tretinoin to one side of their face and benzoyl peroxide/adapalene to the other side once daily for 3 weeks. They kept a daily record scoring burning/stinging and itching on a 0-3 scale. In addition, investigators measured transepidermal water loss and conducted Investigator’s Global Assessments of dryness/scaling and erythema at baseline and weekly thereafter.

The primary study outcome was transepidermal water loss, a reliable and validated measure of epidermal barrier disruption. Transepidermal water loss was significantly greater at weeks 1, 2, and 3 on the benzoyl peroxide/adapalene–treated side of the face.

The benzoyl peroxide/adapalene–treated side also scored threefold higher on the patients’ self-assessed rating of burning/stinging, and twice as high on itching.

“This isn’t entirely surprising, since in studies in atopic dermatitis we also see that there’s a correlation between higher transepidermal water-loss scores and increased pruritus, which is what we saw here,” Dr. Goreshi said.

The difference in composite irritancy scores was larger in the first half of the study than in the second half, when scores headed toward convergence.

Investigators found no significant difference between the two products in erythema or dryness/scaling.

There was also no significant difference between the two topical agents in terms of reduction of acne lesion counts. However, one wouldn’t expect to see significant differences during this short of a study, which was designed to look at irritancy, not efficacy, Dr. Goreshi noted.

The study was funded by Medicis, which markets Ziana.

NEW ORLEANS – High school and college students frequently misuse methylphenidate and dextroamphetamine/amphetamine for the purpose of weight loss, a study has shown.

Students are known to commonly misuse prescription stimulants to enhance concentration and alertness before a big exam or term paper. Most college students who admitted to misusing these drugs for weight loss also reported engaging in other unhealthy weight loss behaviors, some of which are strongly suggestive of an underlying eating disorder, according to Amy J. Jeffers, a graduate student in psychology at Virginia Commonwealth University, Richmond.

For example, more than 20% of students using prescription stimulants in an effort to lose weight indicated they had also used laxatives or diuretics for the same purpose. A similar proportion reported having deliberately induced vomiting toward that end.

An anonymous 30-minute online survey was completed by 705 students at a large university, 26% of whom indicated they were currently dieting. Overall, misuse of prescription stimulants for the purpose of weight loss was reported by 11.7% of respondents: 13.1% of women and 9.7% of men. White students were significantly more likely to have engaged in this practice than blacks by a margin of 14.6% to 8.9%.

Roughly 60% or more of students who misused prescription stimulants for weight loss indicated they had also skipped meals, engaged in excessive physical exercise, or tried fad diets in an effort to lose weight. These unhealthy weight loss behaviors were much less common among students who did not use prescription stimulants for weight loss.

Individuals who misused prescription stimulants for weight loss frequently differed from those who did not in terms of their motivation for weight loss. They were significantly more likely to express a desire to lose weight for self-image reasons – that is, to feel more attractive. They also scored lower on a validated measure of self-esteem, as well as on the three subscales of the Eating and Appraisal Due to Emotions and Stress (EADES) Questionnaire, which is indicative of a compromised ability to cope with stress.

Physicians prescribing these medications for their approved indications may want to consider emphasizing the potential harmful effects of misusing the drugs for weight loss, she said.

Ms. Jeffers reported having no relevant financial conflicts.

NEW ORLEANS – High school and college students frequently misuse methylphenidate and dextroamphetamine/amphetamine for the purpose of weight loss, a study has shown.

Students are known to commonly misuse prescription stimulants to enhance concentration and alertness before a big exam or term paper. Most college students who admitted to misusing these drugs for weight loss also reported engaging in other unhealthy weight loss behaviors, some of which are strongly suggestive of an underlying eating disorder, according to Amy J. Jeffers, a graduate student in psychology at Virginia Commonwealth University, Richmond.

For example, more than 20% of students using prescription stimulants in an effort to lose weight indicated they had also used laxatives or diuretics for the same purpose. A similar proportion reported having deliberately induced vomiting toward that end.

An anonymous 30-minute online survey was completed by 705 students at a large university, 26% of whom indicated they were currently dieting. Overall, misuse of prescription stimulants for the purpose of weight loss was reported by 11.7% of respondents: 13.1% of women and 9.7% of men. White students were significantly more likely to have engaged in this practice than blacks by a margin of 14.6% to 8.9%.

Roughly 60% or more of students who misused prescription stimulants for weight loss indicated they had also skipped meals, engaged in excessive physical exercise, or tried fad diets in an effort to lose weight. These unhealthy weight loss behaviors were much less common among students who did not use prescription stimulants for weight loss.

Individuals who misused prescription stimulants for weight loss frequently differed from those who did not in terms of their motivation for weight loss. They were significantly more likely to express a desire to lose weight for self-image reasons – that is, to feel more attractive. They also scored lower on a validated measure of self-esteem, as well as on the three subscales of the Eating and Appraisal Due to Emotions and Stress (EADES) Questionnaire, which is indicative of a compromised ability to cope with stress.

Physicians prescribing these medications for their approved indications may want to consider emphasizing the potential harmful effects of misusing the drugs for weight loss, she said.

Ms. Jeffers reported having no relevant financial conflicts.

NEW ORLEANS – High school and college students frequently misuse methylphenidate and dextroamphetamine/amphetamine for the purpose of weight loss, a study has shown.

Students are known to commonly misuse prescription stimulants to enhance concentration and alertness before a big exam or term paper. Most college students who admitted to misusing these drugs for weight loss also reported engaging in other unhealthy weight loss behaviors, some of which are strongly suggestive of an underlying eating disorder, according to Amy J. Jeffers, a graduate student in psychology at Virginia Commonwealth University, Richmond.

For example, more than 20% of students using prescription stimulants in an effort to lose weight indicated they had also used laxatives or diuretics for the same purpose. A similar proportion reported having deliberately induced vomiting toward that end.

An anonymous 30-minute online survey was completed by 705 students at a large university, 26% of whom indicated they were currently dieting. Overall, misuse of prescription stimulants for the purpose of weight loss was reported by 11.7% of respondents: 13.1% of women and 9.7% of men. White students were significantly more likely to have engaged in this practice than blacks by a margin of 14.6% to 8.9%.

Roughly 60% or more of students who misused prescription stimulants for weight loss indicated they had also skipped meals, engaged in excessive physical exercise, or tried fad diets in an effort to lose weight. These unhealthy weight loss behaviors were much less common among students who did not use prescription stimulants for weight loss.

Individuals who misused prescription stimulants for weight loss frequently differed from those who did not in terms of their motivation for weight loss. They were significantly more likely to express a desire to lose weight for self-image reasons – that is, to feel more attractive. They also scored lower on a validated measure of self-esteem, as well as on the three subscales of the Eating and Appraisal Due to Emotions and Stress (EADES) Questionnaire, which is indicative of a compromised ability to cope with stress.

Physicians prescribing these medications for their approved indications may want to consider emphasizing the potential harmful effects of misusing the drugs for weight loss, she said.

Ms. Jeffers reported having no relevant financial conflicts.

RALEIGH, N.C. – A new once-daily topical gel containing a proprietary onion extract resulted in a 36% improvement in the appearance of recent postsurgical dermal scars at 8 weeks, according to the results of a randomized, controlled trial.

The over-the-counter product, Merz Pharmaceuticals’ Mederma Advanced Scar Gel, was studied in 44 adults, each of whom underwent surgical shave removal of two similar-size seborrheic keratoses on the chest. At 2 weeks, after the wounds had reepithelialized, patients were randomly assigned to apply the nonprescription onion extract gel once daily to one scar and no treatment to the other.

Blinded investigator assessment was carried out after 2, 4, and 8 weeks of once-daily therapy. Each scar was graded on a 0-3 scale for improvement over baseline for overall appearance and for more specific individual domains of texture, redness, and softness. Patients independently carried out the same assessments, explained Dr. Zoe D. Draelos, a clinical dermatologist and researcher in High Point, N.C.

At week 8, investigators rated the onion extract–treated scars as demonstrating a mean 2.6-point improvement over baseline in terms of overall appearance, with comparable improvements noted in texture, redness, and scar softness. These were significantly better outcomes than was the mean 2.1-point improvement in the overall appearance of untreated control scars, she noted.

The patients rated the onion extract gel–treated scars as showing a mean 2.0-point improvement at week 8, significantly better than the 1.5-point improvement noted in the control scars.

Although optimal results were seen at week 8, the topical gel–treated scars showed a significant advantage in appearance scores, compared with control scars, as early as week 4, with a nonsignificant favorable trend noted at week 2.

The chief advantage that the transparent onion extract gel offers over other scar treatment products is the convenience of once-daily application, noted Dr. Draelos.

Merz announced the launch of Mederma Advanced Scar Gel in the spring. It is available in the first-aid section of pharmacies nationwide at a retail price of about $20 for a 20-g tube and $32 for 50 g, according to the company.

Other Merz products containing Cepalin, the proprietary onion extract, include Mederma Scar Cream plus SPF 30, Mederma for Kids, and Mederma Stretch Marks Therapy.

Dr. Draelos received research funding from Merz to conduct the clinical trial.

RALEIGH, N.C. – A new once-daily topical gel containing a proprietary onion extract resulted in a 36% improvement in the appearance of recent postsurgical dermal scars at 8 weeks, according to the results of a randomized, controlled trial.

The over-the-counter product, Merz Pharmaceuticals’ Mederma Advanced Scar Gel, was studied in 44 adults, each of whom underwent surgical shave removal of two similar-size seborrheic keratoses on the chest. At 2 weeks, after the wounds had reepithelialized, patients were randomly assigned to apply the nonprescription onion extract gel once daily to one scar and no treatment to the other.

Blinded investigator assessment was carried out after 2, 4, and 8 weeks of once-daily therapy. Each scar was graded on a 0-3 scale for improvement over baseline for overall appearance and for more specific individual domains of texture, redness, and softness. Patients independently carried out the same assessments, explained Dr. Zoe D. Draelos, a clinical dermatologist and researcher in High Point, N.C.

At week 8, investigators rated the onion extract–treated scars as demonstrating a mean 2.6-point improvement over baseline in terms of overall appearance, with comparable improvements noted in texture, redness, and scar softness. These were significantly better outcomes than was the mean 2.1-point improvement in the overall appearance of untreated control scars, she noted.

The patients rated the onion extract gel–treated scars as showing a mean 2.0-point improvement at week 8, significantly better than the 1.5-point improvement noted in the control scars.

Although optimal results were seen at week 8, the topical gel–treated scars showed a significant advantage in appearance scores, compared with control scars, as early as week 4, with a nonsignificant favorable trend noted at week 2.

The chief advantage that the transparent onion extract gel offers over other scar treatment products is the convenience of once-daily application, noted Dr. Draelos.

Merz announced the launch of Mederma Advanced Scar Gel in the spring. It is available in the first-aid section of pharmacies nationwide at a retail price of about $20 for a 20-g tube and $32 for 50 g, according to the company.

Other Merz products containing Cepalin, the proprietary onion extract, include Mederma Scar Cream plus SPF 30, Mederma for Kids, and Mederma Stretch Marks Therapy.

Dr. Draelos received research funding from Merz to conduct the clinical trial.

RALEIGH, N.C. – A new once-daily topical gel containing a proprietary onion extract resulted in a 36% improvement in the appearance of recent postsurgical dermal scars at 8 weeks, according to the results of a randomized, controlled trial.

The over-the-counter product, Merz Pharmaceuticals’ Mederma Advanced Scar Gel, was studied in 44 adults, each of whom underwent surgical shave removal of two similar-size seborrheic keratoses on the chest. At 2 weeks, after the wounds had reepithelialized, patients were randomly assigned to apply the nonprescription onion extract gel once daily to one scar and no treatment to the other.

Blinded investigator assessment was carried out after 2, 4, and 8 weeks of once-daily therapy. Each scar was graded on a 0-3 scale for improvement over baseline for overall appearance and for more specific individual domains of texture, redness, and softness. Patients independently carried out the same assessments, explained Dr. Zoe D. Draelos, a clinical dermatologist and researcher in High Point, N.C.

At week 8, investigators rated the onion extract–treated scars as demonstrating a mean 2.6-point improvement over baseline in terms of overall appearance, with comparable improvements noted in texture, redness, and scar softness. These were significantly better outcomes than was the mean 2.1-point improvement in the overall appearance of untreated control scars, she noted.

The patients rated the onion extract gel–treated scars as showing a mean 2.0-point improvement at week 8, significantly better than the 1.5-point improvement noted in the control scars.

Although optimal results were seen at week 8, the topical gel–treated scars showed a significant advantage in appearance scores, compared with control scars, as early as week 4, with a nonsignificant favorable trend noted at week 2.

The chief advantage that the transparent onion extract gel offers over other scar treatment products is the convenience of once-daily application, noted Dr. Draelos.

Merz announced the launch of Mederma Advanced Scar Gel in the spring. It is available in the first-aid section of pharmacies nationwide at a retail price of about $20 for a 20-g tube and $32 for 50 g, according to the company.

Other Merz products containing Cepalin, the proprietary onion extract, include Mederma Scar Cream plus SPF 30, Mederma for Kids, and Mederma Stretch Marks Therapy.

Dr. Draelos received research funding from Merz to conduct the clinical trial.

RALEIGH, N.C. – Postmenopausal women who used aspirin regularly had a significantly reduced risk of developing melanoma during long-term prospective follow-up, according to a Women’s Health Initiative observational study analysis.

The magnitude of this risk reduction grew with greater duration of aspirin use, reported Christina A. Gamba, a medical student at Stanford (Calif.) University.

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During 12 years of prospective follow-up, women who at the time of study enrollment reported they had been taking aspirin regularly for less than a year had roughly an 11% reduction in the likelihood of developing incident melanoma, compared with aspirin nonusers. Those who had been using aspirin regularly for 1-4 years at enrollment went on to have a 20% risk reduction. And women on aspirin for 5 years or longer at enrollment were 30% less likely to develop melanoma than nonusers.

These relative risk figures were fully adjusted for age, education, income, skin type, melanoma risk factors, physical activity, vitamin D intake, smoking status, body mass index, sunburn history, time spent outdoors, sunscreen use, and medical indications for aspirin use, such as cardiovascular disease, she noted.

The findings suggest a possible chemopreventive effect for aspirin against the development of melanoma. As such, these data are consistent with other studies that have linked NSAIDs with decreased risks of breast, colorectal, and gastric cancer. The specific mechanism of benefit is thought to involve inhibition of cyclo-oxygenase-2, which is proinflammatory.

Ms. Gamba explained that her Women’s Health Initiative observational study analysis included 59,806 postmenopausal white women for whom complete pertinent data were available. During nearly 12 years of follow-up, 548 incident melanomas occurred among the study population: 255 were invasive; the rest were in situ.

At enrollment, 25% of women reported using aspirin regularly; their melanoma incidence during follow-up was 0.76%. Fifteen percent of subjects used nonaspirin NSAIDs; their melanoma incidence was 0.97%, which was identical to the rate in the 60% of women who were nonusers of any NSAIDs. Regular users of acetaminophen, a drug that relieves pain but doesn’t inhibit cyclo-oxygenase-2, had the same melanoma incidence as nonusers of aspirin and other NSAIDs.

Three-quarters of the aspirin users were on regular- or extrastrength formulations. There were too few women on low-dose aspirin to be able to draw any conclusions as to whether it, too, protected against melanoma, she said at the annual meeting of the Society of Investigative Dermatology.

The study included one measure of consistency: At 3 years of follow-up, 60% of women who reported taking aspirin regularly at baseline were still doing so, as were 35% of those who had been on nonaspirin NSAIDs at enrollment.

Audience members posed this question: If aspirin’s presumed chemoprevention mechanism involves the inhibition of cyclooxygenase-2, why didn’t users of nonaspirin NSAIDs enjoy a similar benefit? Ms. Gamba offered two possible theories. One is that users of nonaspirin NSAIDs took the medication less frequently, in contrast to aspirin users who generally took the drug on a daily basis.

The other possibility, she continued, is that aspirin curbs tumorigenesis through cyclo-oxygenase-independent mechanisms – perhaps by promoting apoptotic genes and/or inhibiting tumor-promoting genes.

All cases of melanoma in the Women’s Health Initiative were pathologically confirmed. Ms. Gamba and her investigators are now going back and examining the pathology reports to learn what specific types of melanoma were involved. They are also reanalyzing their aspirin/NSAID usage data, this time restricting the analysis to cases of in situ melanoma.

The Women’s Health Initiative Observational Study was sponsored by the National Institutes of Health. Ms. Gamba reported having no relevant financial conflicts.

RALEIGH, N.C. – Postmenopausal women who used aspirin regularly had a significantly reduced risk of developing melanoma during long-term prospective follow-up, according to a Women’s Health Initiative observational study analysis.

The magnitude of this risk reduction grew with greater duration of aspirin use, reported Christina A. Gamba, a medical student at Stanford (Calif.) University.

©jimdeli/Fotolia.com

During 12 years of prospective follow-up, women who at the time of study enrollment reported they had been taking aspirin regularly for less than a year had roughly an 11% reduction in the likelihood of developing incident melanoma, compared with aspirin nonusers. Those who had been using aspirin regularly for 1-4 years at enrollment went on to have a 20% risk reduction. And women on aspirin for 5 years or longer at enrollment were 30% less likely to develop melanoma than nonusers.

These relative risk figures were fully adjusted for age, education, income, skin type, melanoma risk factors, physical activity, vitamin D intake, smoking status, body mass index, sunburn history, time spent outdoors, sunscreen use, and medical indications for aspirin use, such as cardiovascular disease, she noted.

The findings suggest a possible chemopreventive effect for aspirin against the development of melanoma. As such, these data are consistent with other studies that have linked NSAIDs with decreased risks of breast, colorectal, and gastric cancer. The specific mechanism of benefit is thought to involve inhibition of cyclo-oxygenase-2, which is proinflammatory.

Ms. Gamba explained that her Women’s Health Initiative observational study analysis included 59,806 postmenopausal white women for whom complete pertinent data were available. During nearly 12 years of follow-up, 548 incident melanomas occurred among the study population: 255 were invasive; the rest were in situ.

At enrollment, 25% of women reported using aspirin regularly; their melanoma incidence during follow-up was 0.76%. Fifteen percent of subjects used nonaspirin NSAIDs; their melanoma incidence was 0.97%, which was identical to the rate in the 60% of women who were nonusers of any NSAIDs. Regular users of acetaminophen, a drug that relieves pain but doesn’t inhibit cyclo-oxygenase-2, had the same melanoma incidence as nonusers of aspirin and other NSAIDs.

Three-quarters of the aspirin users were on regular- or extrastrength formulations. There were too few women on low-dose aspirin to be able to draw any conclusions as to whether it, too, protected against melanoma, she said at the annual meeting of the Society of Investigative Dermatology.

The study included one measure of consistency: At 3 years of follow-up, 60% of women who reported taking aspirin regularly at baseline were still doing so, as were 35% of those who had been on nonaspirin NSAIDs at enrollment.

Audience members posed this question: If aspirin’s presumed chemoprevention mechanism involves the inhibition of cyclooxygenase-2, why didn’t users of nonaspirin NSAIDs enjoy a similar benefit? Ms. Gamba offered two possible theories. One is that users of nonaspirin NSAIDs took the medication less frequently, in contrast to aspirin users who generally took the drug on a daily basis.

The other possibility, she continued, is that aspirin curbs tumorigenesis through cyclo-oxygenase-independent mechanisms – perhaps by promoting apoptotic genes and/or inhibiting tumor-promoting genes.

All cases of melanoma in the Women’s Health Initiative were pathologically confirmed. Ms. Gamba and her investigators are now going back and examining the pathology reports to learn what specific types of melanoma were involved. They are also reanalyzing their aspirin/NSAID usage data, this time restricting the analysis to cases of in situ melanoma.

The Women’s Health Initiative Observational Study was sponsored by the National Institutes of Health. Ms. Gamba reported having no relevant financial conflicts.

RALEIGH, N.C. – Postmenopausal women who used aspirin regularly had a significantly reduced risk of developing melanoma during long-term prospective follow-up, according to a Women’s Health Initiative observational study analysis.

The magnitude of this risk reduction grew with greater duration of aspirin use, reported Christina A. Gamba, a medical student at Stanford (Calif.) University.

©jimdeli/Fotolia.com

During 12 years of prospective follow-up, women who at the time of study enrollment reported they had been taking aspirin regularly for less than a year had roughly an 11% reduction in the likelihood of developing incident melanoma, compared with aspirin nonusers. Those who had been using aspirin regularly for 1-4 years at enrollment went on to have a 20% risk reduction. And women on aspirin for 5 years or longer at enrollment were 30% less likely to develop melanoma than nonusers.

These relative risk figures were fully adjusted for age, education, income, skin type, melanoma risk factors, physical activity, vitamin D intake, smoking status, body mass index, sunburn history, time spent outdoors, sunscreen use, and medical indications for aspirin use, such as cardiovascular disease, she noted.

The findings suggest a possible chemopreventive effect for aspirin against the development of melanoma. As such, these data are consistent with other studies that have linked NSAIDs with decreased risks of breast, colorectal, and gastric cancer. The specific mechanism of benefit is thought to involve inhibition of cyclo-oxygenase-2, which is proinflammatory.

Ms. Gamba explained that her Women’s Health Initiative observational study analysis included 59,806 postmenopausal white women for whom complete pertinent data were available. During nearly 12 years of follow-up, 548 incident melanomas occurred among the study population: 255 were invasive; the rest were in situ.

At enrollment, 25% of women reported using aspirin regularly; their melanoma incidence during follow-up was 0.76%. Fifteen percent of subjects used nonaspirin NSAIDs; their melanoma incidence was 0.97%, which was identical to the rate in the 60% of women who were nonusers of any NSAIDs. Regular users of acetaminophen, a drug that relieves pain but doesn’t inhibit cyclo-oxygenase-2, had the same melanoma incidence as nonusers of aspirin and other NSAIDs.

Three-quarters of the aspirin users were on regular- or extrastrength formulations. There were too few women on low-dose aspirin to be able to draw any conclusions as to whether it, too, protected against melanoma, she said at the annual meeting of the Society of Investigative Dermatology.

The study included one measure of consistency: At 3 years of follow-up, 60% of women who reported taking aspirin regularly at baseline were still doing so, as were 35% of those who had been on nonaspirin NSAIDs at enrollment.

Audience members posed this question: If aspirin’s presumed chemoprevention mechanism involves the inhibition of cyclooxygenase-2, why didn’t users of nonaspirin NSAIDs enjoy a similar benefit? Ms. Gamba offered two possible theories. One is that users of nonaspirin NSAIDs took the medication less frequently, in contrast to aspirin users who generally took the drug on a daily basis.

The other possibility, she continued, is that aspirin curbs tumorigenesis through cyclo-oxygenase-independent mechanisms – perhaps by promoting apoptotic genes and/or inhibiting tumor-promoting genes.

All cases of melanoma in the Women’s Health Initiative were pathologically confirmed. Ms. Gamba and her investigators are now going back and examining the pathology reports to learn what specific types of melanoma were involved. They are also reanalyzing their aspirin/NSAID usage data, this time restricting the analysis to cases of in situ melanoma.

The Women’s Health Initiative Observational Study was sponsored by the National Institutes of Health. Ms. Gamba reported having no relevant financial conflicts.

NEW ORLEANS – Residents in obstetrics and gynecology appear to have sizeable deficiencies in statistical literacy, results of a national survey suggests.

A survey completed by 4,713 ob.gyn. residents in 2011 included two questions aimed at assessing their statistical knowledge. The residents’ performance in this area, overall, "was not good," according to Britta L. Anderson, Ph.D. who works in the research department of the American College of Obstetricians and Gynecologists, Washington.

Indeed, on a multiple-choice question asking residents to identify the positive predictive value of a positive screening mammogram, a mere 26% picked the correct answer.

The other question was true/false. It asked whether the P value is the probability that the null hypothesis is correct. Only 42% of ob.gyn. residents correctly responded ‘no.’

These were not trick questions. A patient’s ability to make informed medical decisions depends upon her physician’s ability to effectively communicate numerical information. And based upon the high wrong-answer rates to the two survey questions on statistics, most ob.gyns.-in-training are on shaky ground in this area, according to Dr. Anderson. She noted that statistical literacy is going to be increasingly important to clinicians as evidence-based medicine moves to the fore.

The survey also asked ob.gyn. residents if they thought their statistical literacy training was adequate, and how they obtained it.

In all, 81% of survey respondents were women, 25% of whom deemed their statistical literacy training inadequate. In contrast, only 18% of male ob.gyn. residents characterized their training in this area as inadequate.

As to where they received their training in statistical literacy, 42% of residents indicated it came solely through participation in journal club, 12% said their training came entirely through course work, 22% indicated their training was solely informal, and 15% said they had received no training at all in statistical literacy. The remaining residents said their familiarity with statistics came from various combinations of journal club, course work, and informal sources.

Dr. Anderson reported having no financial conflicts.

NEW ORLEANS – Residents in obstetrics and gynecology appear to have sizeable deficiencies in statistical literacy, results of a national survey suggests.

A survey completed by 4,713 ob.gyn. residents in 2011 included two questions aimed at assessing their statistical knowledge. The residents’ performance in this area, overall, "was not good," according to Britta L. Anderson, Ph.D. who works in the research department of the American College of Obstetricians and Gynecologists, Washington.

Indeed, on a multiple-choice question asking residents to identify the positive predictive value of a positive screening mammogram, a mere 26% picked the correct answer.

The other question was true/false. It asked whether the P value is the probability that the null hypothesis is correct. Only 42% of ob.gyn. residents correctly responded ‘no.’

These were not trick questions. A patient’s ability to make informed medical decisions depends upon her physician’s ability to effectively communicate numerical information. And based upon the high wrong-answer rates to the two survey questions on statistics, most ob.gyns.-in-training are on shaky ground in this area, according to Dr. Anderson. She noted that statistical literacy is going to be increasingly important to clinicians as evidence-based medicine moves to the fore.

The survey also asked ob.gyn. residents if they thought their statistical literacy training was adequate, and how they obtained it.

In all, 81% of survey respondents were women, 25% of whom deemed their statistical literacy training inadequate. In contrast, only 18% of male ob.gyn. residents characterized their training in this area as inadequate.

As to where they received their training in statistical literacy, 42% of residents indicated it came solely through participation in journal club, 12% said their training came entirely through course work, 22% indicated their training was solely informal, and 15% said they had received no training at all in statistical literacy. The remaining residents said their familiarity with statistics came from various combinations of journal club, course work, and informal sources.

Dr. Anderson reported having no financial conflicts.

NEW ORLEANS – Residents in obstetrics and gynecology appear to have sizeable deficiencies in statistical literacy, results of a national survey suggests.

A survey completed by 4,713 ob.gyn. residents in 2011 included two questions aimed at assessing their statistical knowledge. The residents’ performance in this area, overall, "was not good," according to Britta L. Anderson, Ph.D. who works in the research department of the American College of Obstetricians and Gynecologists, Washington.

Indeed, on a multiple-choice question asking residents to identify the positive predictive value of a positive screening mammogram, a mere 26% picked the correct answer.

The other question was true/false. It asked whether the P value is the probability that the null hypothesis is correct. Only 42% of ob.gyn. residents correctly responded ‘no.’

These were not trick questions. A patient’s ability to make informed medical decisions depends upon her physician’s ability to effectively communicate numerical information. And based upon the high wrong-answer rates to the two survey questions on statistics, most ob.gyns.-in-training are on shaky ground in this area, according to Dr. Anderson. She noted that statistical literacy is going to be increasingly important to clinicians as evidence-based medicine moves to the fore.

The survey also asked ob.gyn. residents if they thought their statistical literacy training was adequate, and how they obtained it.

In all, 81% of survey respondents were women, 25% of whom deemed their statistical literacy training inadequate. In contrast, only 18% of male ob.gyn. residents characterized their training in this area as inadequate.

As to where they received their training in statistical literacy, 42% of residents indicated it came solely through participation in journal club, 12% said their training came entirely through course work, 22% indicated their training was solely informal, and 15% said they had received no training at all in statistical literacy. The remaining residents said their familiarity with statistics came from various combinations of journal club, course work, and informal sources.

Dr. Anderson reported having no financial conflicts.