Denise Napoli

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Mycophenolate mofetil was associated with stabilization or improvement of predicted forced vital capacity in patients with connective tissue disease-associated interstitial lung disease. Moreover, the drug was safe and well tolerated in this population over a median 2.5 years of use, according to a study published online in the Journal of Rheumatology.

Dr. Aryeh Fischer of the autoimmune and interstitial lung disease program at National Jewish Health in Denver and colleagues looked at the medical records of all patients who received mycophenolate mofetil (MMF) and were treated by an interstitial lung disease specialist at his facility between January 2008 and January 2011.

Dr. Aryeh Fischer

In total, 125 of these patients had connective tissue disease–associated interstitial lung disease (CTD-ILD), plus 6 months of follow-up data (J. Rheumatol. 1 Mar. 2013 [doi:10.3899/jrheum.121043]).

Patients’ mean age was 60.4 years; 42% were female and 83% were white.

A total of 44 of these patients had systemic sclerosis, 32 had polymyositis/dermatomyositis, 19 had lung-dominant connective tissue disease, 18 had rheumatoid arthritis, 5 had Sjögren disease, 4 had systemic lupus erythematosus, and 3 had mixed connective tissue disease.

Most subjects took 3,000 mg/day (65%) of MMF, with none exceeding that dosage and only four subjects taking less than 2,000 mg/day.

Overall, the authors reported that, over a median duration of MMF use of 897 days (2.5 years), only 13 subjects discontinued the drug, citing gastrointestinal intolerance, ILD progression, hepatic transaminase elevation, recurrent infections, and cytopenias.

Even among those who discontinued the drug, however, the median duration of use was still more than 2 years, at 763 days.

Dr. Fischer and his associates then looked at changes in pulmonary physiology. Over the 156 weeks prior to MMF initiation, a mixed-effects model of the entire cohort showed no significant changes in either estimated percentage of predicted forced vital capacity for sex, ethnicity, age, and height (FVC%) or the estimated percentage of predicted diffusing capacity for sex, ethnicity, age, and height (DLCO%).

At 52 weeks, however, there was a mean increase in FVC% of 4.9% (P = .01) and of DLCO% of 6.3% (P = .02), they reported. At 104 weeks after initiation of MMF, the change in FVC% had increased to 6.1% (P = .0008), and at 156 weeks, it had improved 7.3% from baseline (P = .004).

Similarly, by 104 weeks, the DLCO% had increased by 7.1% (P = .01); at 156 weeks, there was a mean 7.8% change from baseline (P = .05).

Patients taking MMF were able to taper prednisone doses once they initiated the drug, Dr. Fischer and his associates wrote.

Indeed, according to the researchers, model estimates for mean daily prednisone doses for the entire cohort at 52 and 26 weeks before MMF initiation were 14 and 7 mg, respectively. At MMF initiation, the mean dose was 20 mg/day.

In contrast, "estimated prednisone dose at 26 and 52 weeks after MMF initiation was 12 and 5 mg, respectively (P less than .0001 for each, compared to 20 mg at MMF initiation)," they calculated.

Dr. Fischer and his associates conceded several limitations to their study, including its retrospective design.

"From our data, one cannot know whether treatment with other immunosuppressive agents would yield similar results or even whether MMF definitively caused the observed changes in FVC% and DLCO%," they wrote.

"However, it is telling that MMF was well tolerated and efficacious and allowed for corticosteroid tapering," they added. "Prospective studies of MMF are indicated to further define the role of MMF in the treatment of CTD-ILD."

In an e-mail, Dr. Fischer stated that he had no industry disclosures relevant to the current study. He added that he and several coinvestigators are also involved with the Scleroderma Lung Study II, which is investigating mycophenolate mofetil versus oral cyclophosphamide in scleroderma interstitial lung disease and has no industry sponsorship. The present study was partially funded by a grant to one of the investigators from the National Institutes of Health.

Mycophenolate mofetil was associated with stabilization or improvement of predicted forced vital capacity in patients with connective tissue disease-associated interstitial lung disease. Moreover, the drug was safe and well tolerated in this population over a median 2.5 years of use, according to a study published online in the Journal of Rheumatology.

Dr. Aryeh Fischer of the autoimmune and interstitial lung disease program at National Jewish Health in Denver and colleagues looked at the medical records of all patients who received mycophenolate mofetil (MMF) and were treated by an interstitial lung disease specialist at his facility between January 2008 and January 2011.

Dr. Aryeh Fischer

In total, 125 of these patients had connective tissue disease–associated interstitial lung disease (CTD-ILD), plus 6 months of follow-up data (J. Rheumatol. 1 Mar. 2013 [doi:10.3899/jrheum.121043]).

Patients’ mean age was 60.4 years; 42% were female and 83% were white.

A total of 44 of these patients had systemic sclerosis, 32 had polymyositis/dermatomyositis, 19 had lung-dominant connective tissue disease, 18 had rheumatoid arthritis, 5 had Sjögren disease, 4 had systemic lupus erythematosus, and 3 had mixed connective tissue disease.

Most subjects took 3,000 mg/day (65%) of MMF, with none exceeding that dosage and only four subjects taking less than 2,000 mg/day.

Overall, the authors reported that, over a median duration of MMF use of 897 days (2.5 years), only 13 subjects discontinued the drug, citing gastrointestinal intolerance, ILD progression, hepatic transaminase elevation, recurrent infections, and cytopenias.

Even among those who discontinued the drug, however, the median duration of use was still more than 2 years, at 763 days.

Dr. Fischer and his associates then looked at changes in pulmonary physiology. Over the 156 weeks prior to MMF initiation, a mixed-effects model of the entire cohort showed no significant changes in either estimated percentage of predicted forced vital capacity for sex, ethnicity, age, and height (FVC%) or the estimated percentage of predicted diffusing capacity for sex, ethnicity, age, and height (DLCO%).

At 52 weeks, however, there was a mean increase in FVC% of 4.9% (P = .01) and of DLCO% of 6.3% (P = .02), they reported. At 104 weeks after initiation of MMF, the change in FVC% had increased to 6.1% (P = .0008), and at 156 weeks, it had improved 7.3% from baseline (P = .004).

Similarly, by 104 weeks, the DLCO% had increased by 7.1% (P = .01); at 156 weeks, there was a mean 7.8% change from baseline (P = .05).

Patients taking MMF were able to taper prednisone doses once they initiated the drug, Dr. Fischer and his associates wrote.

Indeed, according to the researchers, model estimates for mean daily prednisone doses for the entire cohort at 52 and 26 weeks before MMF initiation were 14 and 7 mg, respectively. At MMF initiation, the mean dose was 20 mg/day.

In contrast, "estimated prednisone dose at 26 and 52 weeks after MMF initiation was 12 and 5 mg, respectively (P less than .0001 for each, compared to 20 mg at MMF initiation)," they calculated.

Dr. Fischer and his associates conceded several limitations to their study, including its retrospective design.

"From our data, one cannot know whether treatment with other immunosuppressive agents would yield similar results or even whether MMF definitively caused the observed changes in FVC% and DLCO%," they wrote.

"However, it is telling that MMF was well tolerated and efficacious and allowed for corticosteroid tapering," they added. "Prospective studies of MMF are indicated to further define the role of MMF in the treatment of CTD-ILD."

In an e-mail, Dr. Fischer stated that he had no industry disclosures relevant to the current study. He added that he and several coinvestigators are also involved with the Scleroderma Lung Study II, which is investigating mycophenolate mofetil versus oral cyclophosphamide in scleroderma interstitial lung disease and has no industry sponsorship. The present study was partially funded by a grant to one of the investigators from the National Institutes of Health.

Mycophenolate mofetil was associated with stabilization or improvement of predicted forced vital capacity in patients with connective tissue disease-associated interstitial lung disease. Moreover, the drug was safe and well tolerated in this population over a median 2.5 years of use, according to a study published online in the Journal of Rheumatology.

Dr. Aryeh Fischer of the autoimmune and interstitial lung disease program at National Jewish Health in Denver and colleagues looked at the medical records of all patients who received mycophenolate mofetil (MMF) and were treated by an interstitial lung disease specialist at his facility between January 2008 and January 2011.

Dr. Aryeh Fischer

In total, 125 of these patients had connective tissue disease–associated interstitial lung disease (CTD-ILD), plus 6 months of follow-up data (J. Rheumatol. 1 Mar. 2013 [doi:10.3899/jrheum.121043]).

Patients’ mean age was 60.4 years; 42% were female and 83% were white.

A total of 44 of these patients had systemic sclerosis, 32 had polymyositis/dermatomyositis, 19 had lung-dominant connective tissue disease, 18 had rheumatoid arthritis, 5 had Sjögren disease, 4 had systemic lupus erythematosus, and 3 had mixed connective tissue disease.

Most subjects took 3,000 mg/day (65%) of MMF, with none exceeding that dosage and only four subjects taking less than 2,000 mg/day.

Overall, the authors reported that, over a median duration of MMF use of 897 days (2.5 years), only 13 subjects discontinued the drug, citing gastrointestinal intolerance, ILD progression, hepatic transaminase elevation, recurrent infections, and cytopenias.

Even among those who discontinued the drug, however, the median duration of use was still more than 2 years, at 763 days.

Dr. Fischer and his associates then looked at changes in pulmonary physiology. Over the 156 weeks prior to MMF initiation, a mixed-effects model of the entire cohort showed no significant changes in either estimated percentage of predicted forced vital capacity for sex, ethnicity, age, and height (FVC%) or the estimated percentage of predicted diffusing capacity for sex, ethnicity, age, and height (DLCO%).

At 52 weeks, however, there was a mean increase in FVC% of 4.9% (P = .01) and of DLCO% of 6.3% (P = .02), they reported. At 104 weeks after initiation of MMF, the change in FVC% had increased to 6.1% (P = .0008), and at 156 weeks, it had improved 7.3% from baseline (P = .004).

Similarly, by 104 weeks, the DLCO% had increased by 7.1% (P = .01); at 156 weeks, there was a mean 7.8% change from baseline (P = .05).

Patients taking MMF were able to taper prednisone doses once they initiated the drug, Dr. Fischer and his associates wrote.

Indeed, according to the researchers, model estimates for mean daily prednisone doses for the entire cohort at 52 and 26 weeks before MMF initiation were 14 and 7 mg, respectively. At MMF initiation, the mean dose was 20 mg/day.

In contrast, "estimated prednisone dose at 26 and 52 weeks after MMF initiation was 12 and 5 mg, respectively (P less than .0001 for each, compared to 20 mg at MMF initiation)," they calculated.

Dr. Fischer and his associates conceded several limitations to their study, including its retrospective design.

"From our data, one cannot know whether treatment with other immunosuppressive agents would yield similar results or even whether MMF definitively caused the observed changes in FVC% and DLCO%," they wrote.

"However, it is telling that MMF was well tolerated and efficacious and allowed for corticosteroid tapering," they added. "Prospective studies of MMF are indicated to further define the role of MMF in the treatment of CTD-ILD."

In an e-mail, Dr. Fischer stated that he had no industry disclosures relevant to the current study. He added that he and several coinvestigators are also involved with the Scleroderma Lung Study II, which is investigating mycophenolate mofetil versus oral cyclophosphamide in scleroderma interstitial lung disease and has no industry sponsorship. The present study was partially funded by a grant to one of the investigators from the National Institutes of Health.

Global Assessment of Functioning scores are not sensitive to variations in social cognition among patients with schizophrenia, a major part of "real world outcomes" for this population, a study has shown.

Indeed, "although the GAF scale is reported to be a valid measure of function and, as such, a useful tool for clinicians to assess patients’ progress in rehabilitation, it is a less sensitive tool for establishing and monitoring improvements in function associated with social aspects of cognition," wrote Deirdre A. Robertson in an article published online in Schizophrenia Research (2013 [http://dx.doi.org/10.1016/j.schres.2013.01.016]).

According to Ms. Robertson, a PhD candidate at Trinity College Dublin, and her colleagues, although the GAF is widely used, "it is unclear if the GAF scale is a reliable tool for assessing the functional difficulties associated with more subtle impairments in social cognition" in schizophrenia, once investigators control for the outward presentation of positive and negative symptoms.

To test this hypothesis, Ms. Robertson enrolled 216 patients from the Resource for Psychosis Genomics, Ireland, initiative with schizophrenia or schizoaffective diagnoses recruited from sites across Ireland.

Social cognition was measured using two "theory of mind" tasks. The first was the reading the mind in the eyes test, in which subjects rate 36 photographs of eyes portraying different expressions and correctly identify the thought or feeling as one of four descriptors printed around each photograph.

The second was the hinting task, in which participants listen to 10 vignettes describing social interactions and infer the intent behind the hint after each vignette.

Patients also were scored according to a neurocognition composite score sensitive to deficits typically seen in schizophrenia – intelligence quotient, episodic memory, working memory, and attentional control.

Finally, the researchers used linear regression analyses to assess the degree of variance in global functioning explained by symptom severity, medication, neurocognition as represented on the composite score, and social cognition.

First, the authors found that scores on the GAF scale were significantly positively correlated with the hinting task, but not with the eyes task, so that the latter was excluded from further analysis.

Then, the authors performed a regression analysis with symptom severity entered on the first step, followed by neurocognitive and hinting task performance on the second step and GAF scores entered as the dependent variable.

"After the 25.2% of variation in GAF scores explained by symptom severity, neurocognitive performance explained an additional 4.7% of variation, while the hinting task failed to explain any further variation," they wrote.

According to the researchers, one limitation of their study was the use of only one social cognitive domain, theory of mind. Indeed, "it is possible that the GAF scale may have been more sensitive to social cognition deficits in emotion perception/recognition or social knowledge," they wrote, which would have been better perceived on some other domain.

However, the investigators chose to focus solely on theory of mind for two reasons: A 2011 meta-analysis [(Neurosci. Biobehav. Rev. 2011;35:573-88)] reported that theory of mind was the social cognitive domain that explained the largest amount of variance in functioning, and "a previous study from our group demonstrated that theory of mind mediated the relationship between basic neuropsychological function and functional outcome using another measure of functional outcome, the Independent Living Scale."

They concluded that, given their findings, "it is likely that as our understanding of social cognition increases and as remediation program[s] become more frequently incorporated into treatment plans for schizophrenia, a new scale will be needed for clinical use which can more sensitively monitor progress in these domains than the largely symptomatically based GAF scale."

Individual researchers were supported by the Wellcome Trust, Science Foundation Ireland, and Ireland’s Health Research Board. The authors stated they had no conflicts of interest or other funding.

Global Assessment of Functioning scores are not sensitive to variations in social cognition among patients with schizophrenia, a major part of "real world outcomes" for this population, a study has shown.

Indeed, "although the GAF scale is reported to be a valid measure of function and, as such, a useful tool for clinicians to assess patients’ progress in rehabilitation, it is a less sensitive tool for establishing and monitoring improvements in function associated with social aspects of cognition," wrote Deirdre A. Robertson in an article published online in Schizophrenia Research (2013 [http://dx.doi.org/10.1016/j.schres.2013.01.016]).

According to Ms. Robertson, a PhD candidate at Trinity College Dublin, and her colleagues, although the GAF is widely used, "it is unclear if the GAF scale is a reliable tool for assessing the functional difficulties associated with more subtle impairments in social cognition" in schizophrenia, once investigators control for the outward presentation of positive and negative symptoms.

To test this hypothesis, Ms. Robertson enrolled 216 patients from the Resource for Psychosis Genomics, Ireland, initiative with schizophrenia or schizoaffective diagnoses recruited from sites across Ireland.

Social cognition was measured using two "theory of mind" tasks. The first was the reading the mind in the eyes test, in which subjects rate 36 photographs of eyes portraying different expressions and correctly identify the thought or feeling as one of four descriptors printed around each photograph.

The second was the hinting task, in which participants listen to 10 vignettes describing social interactions and infer the intent behind the hint after each vignette.

Patients also were scored according to a neurocognition composite score sensitive to deficits typically seen in schizophrenia – intelligence quotient, episodic memory, working memory, and attentional control.

Finally, the researchers used linear regression analyses to assess the degree of variance in global functioning explained by symptom severity, medication, neurocognition as represented on the composite score, and social cognition.

First, the authors found that scores on the GAF scale were significantly positively correlated with the hinting task, but not with the eyes task, so that the latter was excluded from further analysis.

Then, the authors performed a regression analysis with symptom severity entered on the first step, followed by neurocognitive and hinting task performance on the second step and GAF scores entered as the dependent variable.

"After the 25.2% of variation in GAF scores explained by symptom severity, neurocognitive performance explained an additional 4.7% of variation, while the hinting task failed to explain any further variation," they wrote.

According to the researchers, one limitation of their study was the use of only one social cognitive domain, theory of mind. Indeed, "it is possible that the GAF scale may have been more sensitive to social cognition deficits in emotion perception/recognition or social knowledge," they wrote, which would have been better perceived on some other domain.

However, the investigators chose to focus solely on theory of mind for two reasons: A 2011 meta-analysis [(Neurosci. Biobehav. Rev. 2011;35:573-88)] reported that theory of mind was the social cognitive domain that explained the largest amount of variance in functioning, and "a previous study from our group demonstrated that theory of mind mediated the relationship between basic neuropsychological function and functional outcome using another measure of functional outcome, the Independent Living Scale."

They concluded that, given their findings, "it is likely that as our understanding of social cognition increases and as remediation program[s] become more frequently incorporated into treatment plans for schizophrenia, a new scale will be needed for clinical use which can more sensitively monitor progress in these domains than the largely symptomatically based GAF scale."

Individual researchers were supported by the Wellcome Trust, Science Foundation Ireland, and Ireland’s Health Research Board. The authors stated they had no conflicts of interest or other funding.

Global Assessment of Functioning scores are not sensitive to variations in social cognition among patients with schizophrenia, a major part of "real world outcomes" for this population, a study has shown.

Indeed, "although the GAF scale is reported to be a valid measure of function and, as such, a useful tool for clinicians to assess patients’ progress in rehabilitation, it is a less sensitive tool for establishing and monitoring improvements in function associated with social aspects of cognition," wrote Deirdre A. Robertson in an article published online in Schizophrenia Research (2013 [http://dx.doi.org/10.1016/j.schres.2013.01.016]).

According to Ms. Robertson, a PhD candidate at Trinity College Dublin, and her colleagues, although the GAF is widely used, "it is unclear if the GAF scale is a reliable tool for assessing the functional difficulties associated with more subtle impairments in social cognition" in schizophrenia, once investigators control for the outward presentation of positive and negative symptoms.

To test this hypothesis, Ms. Robertson enrolled 216 patients from the Resource for Psychosis Genomics, Ireland, initiative with schizophrenia or schizoaffective diagnoses recruited from sites across Ireland.

Social cognition was measured using two "theory of mind" tasks. The first was the reading the mind in the eyes test, in which subjects rate 36 photographs of eyes portraying different expressions and correctly identify the thought or feeling as one of four descriptors printed around each photograph.

The second was the hinting task, in which participants listen to 10 vignettes describing social interactions and infer the intent behind the hint after each vignette.

Patients also were scored according to a neurocognition composite score sensitive to deficits typically seen in schizophrenia – intelligence quotient, episodic memory, working memory, and attentional control.

Finally, the researchers used linear regression analyses to assess the degree of variance in global functioning explained by symptom severity, medication, neurocognition as represented on the composite score, and social cognition.

First, the authors found that scores on the GAF scale were significantly positively correlated with the hinting task, but not with the eyes task, so that the latter was excluded from further analysis.

Then, the authors performed a regression analysis with symptom severity entered on the first step, followed by neurocognitive and hinting task performance on the second step and GAF scores entered as the dependent variable.

"After the 25.2% of variation in GAF scores explained by symptom severity, neurocognitive performance explained an additional 4.7% of variation, while the hinting task failed to explain any further variation," they wrote.

According to the researchers, one limitation of their study was the use of only one social cognitive domain, theory of mind. Indeed, "it is possible that the GAF scale may have been more sensitive to social cognition deficits in emotion perception/recognition or social knowledge," they wrote, which would have been better perceived on some other domain.

However, the investigators chose to focus solely on theory of mind for two reasons: A 2011 meta-analysis [(Neurosci. Biobehav. Rev. 2011;35:573-88)] reported that theory of mind was the social cognitive domain that explained the largest amount of variance in functioning, and "a previous study from our group demonstrated that theory of mind mediated the relationship between basic neuropsychological function and functional outcome using another measure of functional outcome, the Independent Living Scale."

They concluded that, given their findings, "it is likely that as our understanding of social cognition increases and as remediation program[s] become more frequently incorporated into treatment plans for schizophrenia, a new scale will be needed for clinical use which can more sensitively monitor progress in these domains than the largely symptomatically based GAF scale."

Individual researchers were supported by the Wellcome Trust, Science Foundation Ireland, and Ireland’s Health Research Board. The authors stated they had no conflicts of interest or other funding.

Clinical depression is present in 58% of patients at ultrahigh risk for psychosis, and 42% meet the criteria for social phobia, a study has shown.

Moreover, women with an at-risk mental state for psychosis showed significantly more depression than men, according to a study published online in Psychiatry Research (2013 [http://dx.doi.org/10.1016/j.psychres.2013.01.012]).

The finding means that "screening a help-seeking population with depression and anxiety may be effective in detecting patients at [ultrahigh risk] for developing psychosis," particularly in women, wrote the authors.

The study, led by Judith Rietdijk, Ph.D., of the VU University Amsterdam, and her colleagues, looked at patients at ultrahigh risk of psychosis, defined as those belonging to at least one of the following categories: having a schizotypal personality disorder or a first-degree relative with psychosis; experiencing attenuated positive symptoms, such as ideas of reference, odd beliefs, magical thinking, or unusual perceptual experiences; or experiencing a brief psychotic episode of less than or equal to 1 week that resolves without antipsychotic medication.

All patients had enrolled in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) psychosis prevention study, a longitudinal, randomized controlled trial that compared treatment as usual to an add-on cognitive-behavioral therapy targeting psychosis risk symptoms.

Patients in the EDIE-NL study were help seeking, meaning they were from the general population who entered secondary mental health care services, or were patients referred to a specialized academic center offering tertiary care.

The current analysis included 201 patients from that study, with a mean age of 22.7 years. Just over half (51%) were female.

Overall, 117 (58.2%; 72, female) of these 201 patients met the Beck Depression Inventory–II (BDI-II) criteria for clinical depression, and 85 patients (42.3%; 50, female) met the criteria for social phobia, as measured on the Social Interaction Anxiety Scale (SIAS).

A separate analysis of gender found that while 45.5% of men met clinical depression criteria, that figure was 70.6% among ultrahigh-risk women (P less than .001).

Moreover, while only 35.4% of the men demonstrated social anxiety, 49.0% of the women met the SIAS criteria (P less than .05).

Dr. Rietdijk and her colleagues also assessed subclinical psychotic symptoms, as measured by the Comprehensive Assessment of At-Risk Mental State (CAARMS), which uses a semistructured interview to determine the presence, severity, frequency, and distress associated with, and the type of, at-risk mental state symptoms (such as unusual thought, nonbizarre ideas, perceptual abnormalities, and disorganized speech).

Using regression analysis, the investigators found that a higher total score on anxiety symptoms was associated with a higher score on the BDI-II (P = .000), as well as a higher score on the subclinical positive symptoms component of the CAARMS (P = .048).

The investigators also found a gender difference in anxiety symptoms: Among males, only age predicted higher positive symptom scores (P = .010), while among females, anxiety predicted positive symptoms on the CAARMS (P = .038).

"Having an at-risk mental state is often accompanied by depression and social anxiety," the authors concluded, although "anxiety and not depression is associated with the level of subclinical psychotic symptoms, particularly in female patients."

The researchers disclosed that their study was supported by the Netherlands Health Research Council. No individual conflicts of interest were disclosed in relation to this study.

Clinical depression is present in 58% of patients at ultrahigh risk for psychosis, and 42% meet the criteria for social phobia, a study has shown.

Moreover, women with an at-risk mental state for psychosis showed significantly more depression than men, according to a study published online in Psychiatry Research (2013 [http://dx.doi.org/10.1016/j.psychres.2013.01.012]).

The finding means that "screening a help-seeking population with depression and anxiety may be effective in detecting patients at [ultrahigh risk] for developing psychosis," particularly in women, wrote the authors.

The study, led by Judith Rietdijk, Ph.D., of the VU University Amsterdam, and her colleagues, looked at patients at ultrahigh risk of psychosis, defined as those belonging to at least one of the following categories: having a schizotypal personality disorder or a first-degree relative with psychosis; experiencing attenuated positive symptoms, such as ideas of reference, odd beliefs, magical thinking, or unusual perceptual experiences; or experiencing a brief psychotic episode of less than or equal to 1 week that resolves without antipsychotic medication.

All patients had enrolled in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) psychosis prevention study, a longitudinal, randomized controlled trial that compared treatment as usual to an add-on cognitive-behavioral therapy targeting psychosis risk symptoms.

Patients in the EDIE-NL study were help seeking, meaning they were from the general population who entered secondary mental health care services, or were patients referred to a specialized academic center offering tertiary care.

The current analysis included 201 patients from that study, with a mean age of 22.7 years. Just over half (51%) were female.

Overall, 117 (58.2%; 72, female) of these 201 patients met the Beck Depression Inventory–II (BDI-II) criteria for clinical depression, and 85 patients (42.3%; 50, female) met the criteria for social phobia, as measured on the Social Interaction Anxiety Scale (SIAS).

A separate analysis of gender found that while 45.5% of men met clinical depression criteria, that figure was 70.6% among ultrahigh-risk women (P less than .001).

Moreover, while only 35.4% of the men demonstrated social anxiety, 49.0% of the women met the SIAS criteria (P less than .05).

Dr. Rietdijk and her colleagues also assessed subclinical psychotic symptoms, as measured by the Comprehensive Assessment of At-Risk Mental State (CAARMS), which uses a semistructured interview to determine the presence, severity, frequency, and distress associated with, and the type of, at-risk mental state symptoms (such as unusual thought, nonbizarre ideas, perceptual abnormalities, and disorganized speech).

Using regression analysis, the investigators found that a higher total score on anxiety symptoms was associated with a higher score on the BDI-II (P = .000), as well as a higher score on the subclinical positive symptoms component of the CAARMS (P = .048).

The investigators also found a gender difference in anxiety symptoms: Among males, only age predicted higher positive symptom scores (P = .010), while among females, anxiety predicted positive symptoms on the CAARMS (P = .038).

"Having an at-risk mental state is often accompanied by depression and social anxiety," the authors concluded, although "anxiety and not depression is associated with the level of subclinical psychotic symptoms, particularly in female patients."

The researchers disclosed that their study was supported by the Netherlands Health Research Council. No individual conflicts of interest were disclosed in relation to this study.

Clinical depression is present in 58% of patients at ultrahigh risk for psychosis, and 42% meet the criteria for social phobia, a study has shown.

Moreover, women with an at-risk mental state for psychosis showed significantly more depression than men, according to a study published online in Psychiatry Research (2013 [http://dx.doi.org/10.1016/j.psychres.2013.01.012]).

The finding means that "screening a help-seeking population with depression and anxiety may be effective in detecting patients at [ultrahigh risk] for developing psychosis," particularly in women, wrote the authors.

The study, led by Judith Rietdijk, Ph.D., of the VU University Amsterdam, and her colleagues, looked at patients at ultrahigh risk of psychosis, defined as those belonging to at least one of the following categories: having a schizotypal personality disorder or a first-degree relative with psychosis; experiencing attenuated positive symptoms, such as ideas of reference, odd beliefs, magical thinking, or unusual perceptual experiences; or experiencing a brief psychotic episode of less than or equal to 1 week that resolves without antipsychotic medication.

All patients had enrolled in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) psychosis prevention study, a longitudinal, randomized controlled trial that compared treatment as usual to an add-on cognitive-behavioral therapy targeting psychosis risk symptoms.

Patients in the EDIE-NL study were help seeking, meaning they were from the general population who entered secondary mental health care services, or were patients referred to a specialized academic center offering tertiary care.

The current analysis included 201 patients from that study, with a mean age of 22.7 years. Just over half (51%) were female.

Overall, 117 (58.2%; 72, female) of these 201 patients met the Beck Depression Inventory–II (BDI-II) criteria for clinical depression, and 85 patients (42.3%; 50, female) met the criteria for social phobia, as measured on the Social Interaction Anxiety Scale (SIAS).

A separate analysis of gender found that while 45.5% of men met clinical depression criteria, that figure was 70.6% among ultrahigh-risk women (P less than .001).

Moreover, while only 35.4% of the men demonstrated social anxiety, 49.0% of the women met the SIAS criteria (P less than .05).

Dr. Rietdijk and her colleagues also assessed subclinical psychotic symptoms, as measured by the Comprehensive Assessment of At-Risk Mental State (CAARMS), which uses a semistructured interview to determine the presence, severity, frequency, and distress associated with, and the type of, at-risk mental state symptoms (such as unusual thought, nonbizarre ideas, perceptual abnormalities, and disorganized speech).

Using regression analysis, the investigators found that a higher total score on anxiety symptoms was associated with a higher score on the BDI-II (P = .000), as well as a higher score on the subclinical positive symptoms component of the CAARMS (P = .048).

The investigators also found a gender difference in anxiety symptoms: Among males, only age predicted higher positive symptom scores (P = .010), while among females, anxiety predicted positive symptoms on the CAARMS (P = .038).

"Having an at-risk mental state is often accompanied by depression and social anxiety," the authors concluded, although "anxiety and not depression is associated with the level of subclinical psychotic symptoms, particularly in female patients."

The researchers disclosed that their study was supported by the Netherlands Health Research Council. No individual conflicts of interest were disclosed in relation to this study.

Adolescents experiencing negative symptoms prior to first psychotic episode were more likely to have declining social support prior to hospitalization, compared with adolescents who exhibited manic prodromal symptoms.

Indeed, "these results provide initial information on the identification of adolescents at highest risk for experiencing a decline in social support, who therefore may particularly benefit from focused intervention," J. E. DeVylder and R.E, Gearing reported in the journal Psychiatry Research.

Mr. DeVylder, a doctoral candidate at the Columbia University School of Social Work, New York, and Dr. Gearing, also of Columbia, looked at archival data from hospital records of inpatient psychiatric units in Ontario, Canada.

Patients were included if they were younger than 18 years of age at the time of hospital admission, hospitalized for a first episode of a primary psychotic disorder (nonaffective or affective), and discharged between Jan. 1, 1999 and Oct. 31, 2003. About one-third of the participants were born in a foreign country.

Nonfamilial social support was judged to be either declining, stable, or improving during the period prior to hospitalization, based on clinician judgment of peer relationships as well as social support and peer relations information from the patients, hospital staff, and collateral contacts, the authors wrote (Psychiatry Res. 2013 Feb. 28 [doi:10.1016/j.psychres.2013.02.004]).

"Only declining and stable were included in this study as no respondents endorsed an increased number of peer relationships," they added.

A total of 84 patients completed mail-in surveys and had all available information on record relating to social networks prior to hospitalization. Among these, the mean age was 14.7 years, 42.9% were female, and the mean duration of untreated psychosis was 19.7 weeks.

A total of 38 patients were deemed to have stable social networks, while the remaining 46 reported declining networks prior to hospitalization.

The authors reported that patients with declining social support had a significantly longer duration of untreated psychosis (25.4 weeks), compared with patients who had stable support systems (12.6 weeks; P less than .05).

Mr. DeVylder and Dr. Gearing also found that patients who reported declining social support were more likely to experience primarily negative symptoms during this prodromal period and less likely to experience manic symptoms.

"No association was found between gender and social support in this study, in contrast to prior findings [Psychol. Med. 2012;42;769-80] in a larger sample predominantly of adults (mean age 32 years) that males have more severe social disability at first episode of psychosis," the investigators added.

Nor was the presence of depression prior to hospitalization associated with social networks.

The study was hampered by its retrospective design, since it did not "allow us to examine specifically whether the decline in social support occurred following psychosis onset or during the prodromal phase, which has been associated with social impairment, or to determine causality in the associations between symptom profile and social support," the researchers conceded.

Nevertheless, "future studies should further examine the trajectory of change in the early course of psychosis with regards to social support as well as other clinical symptoms, either with adolescents at clinical high risk for psychosis or those in the early stages of overt symptoms."

Mr. DeVylder and Dr. Gearing disclosed no conflicts of interest and no outside funding.

Adolescents experiencing negative symptoms prior to first psychotic episode were more likely to have declining social support prior to hospitalization, compared with adolescents who exhibited manic prodromal symptoms.

Indeed, "these results provide initial information on the identification of adolescents at highest risk for experiencing a decline in social support, who therefore may particularly benefit from focused intervention," J. E. DeVylder and R.E, Gearing reported in the journal Psychiatry Research.

Mr. DeVylder, a doctoral candidate at the Columbia University School of Social Work, New York, and Dr. Gearing, also of Columbia, looked at archival data from hospital records of inpatient psychiatric units in Ontario, Canada.

Patients were included if they were younger than 18 years of age at the time of hospital admission, hospitalized for a first episode of a primary psychotic disorder (nonaffective or affective), and discharged between Jan. 1, 1999 and Oct. 31, 2003. About one-third of the participants were born in a foreign country.

Nonfamilial social support was judged to be either declining, stable, or improving during the period prior to hospitalization, based on clinician judgment of peer relationships as well as social support and peer relations information from the patients, hospital staff, and collateral contacts, the authors wrote (Psychiatry Res. 2013 Feb. 28 [doi:10.1016/j.psychres.2013.02.004]).

"Only declining and stable were included in this study as no respondents endorsed an increased number of peer relationships," they added.

A total of 84 patients completed mail-in surveys and had all available information on record relating to social networks prior to hospitalization. Among these, the mean age was 14.7 years, 42.9% were female, and the mean duration of untreated psychosis was 19.7 weeks.

A total of 38 patients were deemed to have stable social networks, while the remaining 46 reported declining networks prior to hospitalization.

The authors reported that patients with declining social support had a significantly longer duration of untreated psychosis (25.4 weeks), compared with patients who had stable support systems (12.6 weeks; P less than .05).

Mr. DeVylder and Dr. Gearing also found that patients who reported declining social support were more likely to experience primarily negative symptoms during this prodromal period and less likely to experience manic symptoms.

"No association was found between gender and social support in this study, in contrast to prior findings [Psychol. Med. 2012;42;769-80] in a larger sample predominantly of adults (mean age 32 years) that males have more severe social disability at first episode of psychosis," the investigators added.

Nor was the presence of depression prior to hospitalization associated with social networks.

The study was hampered by its retrospective design, since it did not "allow us to examine specifically whether the decline in social support occurred following psychosis onset or during the prodromal phase, which has been associated with social impairment, or to determine causality in the associations between symptom profile and social support," the researchers conceded.

Nevertheless, "future studies should further examine the trajectory of change in the early course of psychosis with regards to social support as well as other clinical symptoms, either with adolescents at clinical high risk for psychosis or those in the early stages of overt symptoms."

Mr. DeVylder and Dr. Gearing disclosed no conflicts of interest and no outside funding.

Adolescents experiencing negative symptoms prior to first psychotic episode were more likely to have declining social support prior to hospitalization, compared with adolescents who exhibited manic prodromal symptoms.

Indeed, "these results provide initial information on the identification of adolescents at highest risk for experiencing a decline in social support, who therefore may particularly benefit from focused intervention," J. E. DeVylder and R.E, Gearing reported in the journal Psychiatry Research.

Mr. DeVylder, a doctoral candidate at the Columbia University School of Social Work, New York, and Dr. Gearing, also of Columbia, looked at archival data from hospital records of inpatient psychiatric units in Ontario, Canada.

Patients were included if they were younger than 18 years of age at the time of hospital admission, hospitalized for a first episode of a primary psychotic disorder (nonaffective or affective), and discharged between Jan. 1, 1999 and Oct. 31, 2003. About one-third of the participants were born in a foreign country.

Nonfamilial social support was judged to be either declining, stable, or improving during the period prior to hospitalization, based on clinician judgment of peer relationships as well as social support and peer relations information from the patients, hospital staff, and collateral contacts, the authors wrote (Psychiatry Res. 2013 Feb. 28 [doi:10.1016/j.psychres.2013.02.004]).

"Only declining and stable were included in this study as no respondents endorsed an increased number of peer relationships," they added.

A total of 84 patients completed mail-in surveys and had all available information on record relating to social networks prior to hospitalization. Among these, the mean age was 14.7 years, 42.9% were female, and the mean duration of untreated psychosis was 19.7 weeks.

A total of 38 patients were deemed to have stable social networks, while the remaining 46 reported declining networks prior to hospitalization.

The authors reported that patients with declining social support had a significantly longer duration of untreated psychosis (25.4 weeks), compared with patients who had stable support systems (12.6 weeks; P less than .05).

Mr. DeVylder and Dr. Gearing also found that patients who reported declining social support were more likely to experience primarily negative symptoms during this prodromal period and less likely to experience manic symptoms.

"No association was found between gender and social support in this study, in contrast to prior findings [Psychol. Med. 2012;42;769-80] in a larger sample predominantly of adults (mean age 32 years) that males have more severe social disability at first episode of psychosis," the investigators added.

Nor was the presence of depression prior to hospitalization associated with social networks.

The study was hampered by its retrospective design, since it did not "allow us to examine specifically whether the decline in social support occurred following psychosis onset or during the prodromal phase, which has been associated with social impairment, or to determine causality in the associations between symptom profile and social support," the researchers conceded.

Nevertheless, "future studies should further examine the trajectory of change in the early course of psychosis with regards to social support as well as other clinical symptoms, either with adolescents at clinical high risk for psychosis or those in the early stages of overt symptoms."

Mr. DeVylder and Dr. Gearing disclosed no conflicts of interest and no outside funding.

Changes in serum alpha-fetoprotein levels over time correlated with the development of hepatocellular carcinoma in hepatitis C patients, wrote Dr. Elliot Lee and his colleagues in the April 1 issue of Clinical Gastroenterology and Hepatology.*

"If confirmed in future studies, these findings could be used to develop individualized risk assessments for clinical use, which could then influence the frequency and type of further testing" in this population, added the researchers (doi:10.1016/j.cgh.2012.11.029).

In what he called "the first large study to demonstrate that patterns of AFP [alpha-fetoprotein] over time are independently associated with HCC [hepatocellular carcinoma] development," Dr. Lee of the University of Michigan, Ann Arbor, looked at patients enrolled in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial, in which hepatitis C patients who were nonresponders to prior antiviral therapy were randomized to receive maintenance pegylated interferon or placebo.

According to the trial protocol, patients were screened every 3 months for the first 3.5 years, then every 6 months thereafter on a voluntary basis, with levels of serum alpha-fetoprotein measured at each visit.

Patients who developed hepatocellular carcinoma were matched to controls without HCC in a 1:3 ratio according to the length of follow-up "in order to exclude bias caused by subjects with longer follow-up time having higher cumulative probability of HCC development, as well as more AFP values available," wrote the authors.

Overall, among 967 subjects with hepatitis C, 82 developed HCC during the study period, with a median of 18 (range, 5-22) AFP tests performed.

Dr. Lee then analyzed the association between the development of HCC and three AFP patterns.

First, the researchers assessed the rate of rise, defined as the patient’s final alpha-fetoprotein level (before study conclusion or HCC development, whichever came first) minus the AFP baseline value (on study entry), all over the follow-up duration divided by 90 days.

He found that this metric was associated with an odds ratio for developing HCC of 1.178 (P less than .001) in a simple logistic regression analysis that accounted for baseline risk factors only, with an area under the receiver-operating characteristic (AUROC) of 0.69.

Next, Dr. Lee calculated the standard deviation of AFP, defined as the standard deviation of all AFP values recorded within each patient.

In the same simple logistic regression, the standard deviation calculation was associated with an odds ratio of 1.026 for HCC per unit increase in standard deviation (P less than .001) and an AUROC of 0.76.

Third, Dr. Lee looked at the most recent AFP value on record. In this case, the odds ratio for developing HCC was 1.012 (also with P less than .001) and an AUROC of 0.76.

Finally, the researchers incorporated both standard deviation and rate of rise of AFP along with baseline age, platelet count, and smoking history to create a "history" model, which had an AUROC of 0.81 – an even better predictor than the models that looked only at one of those factors.

In an attempt to explain their findings, the researchers wrote, "it is intuitively evident why the rate of rise of AFP might be associated with risk of HCC development, but what might explain the association with standard deviation?"

They added, "The biologic basis is unknown, but we theorize that fluctuations in AFP may reflect cycles of damage and regeneration within the liver, and that growth factors involved in regeneration could stimulate hepatocarcinogenesis."

The authors acknowledged that the study had several limitations. "From a practical perspective, these metrics will only be useful once a patient has been followed for at least 2 years in order for the patterns to emerge," they wrote.

Additionally, "this study included only patients with hepatitis C; it is unknown whether these associations would be present among patients with other chronic liver diseases."

The authors said they had no relevant financial disclosures. They disclosed grant support from the National Science Foundation Graduate Research Fellowship.

*Correction, 3/25/2013: An earlier version of this story misstated the name of Clinical Gastroenterology and Hepatology.

Changes in serum alpha-fetoprotein levels over time correlated with the development of hepatocellular carcinoma in hepatitis C patients, wrote Dr. Elliot Lee and his colleagues in the April 1 issue of Clinical Gastroenterology and Hepatology.*

"If confirmed in future studies, these findings could be used to develop individualized risk assessments for clinical use, which could then influence the frequency and type of further testing" in this population, added the researchers (doi:10.1016/j.cgh.2012.11.029).

In what he called "the first large study to demonstrate that patterns of AFP [alpha-fetoprotein] over time are independently associated with HCC [hepatocellular carcinoma] development," Dr. Lee of the University of Michigan, Ann Arbor, looked at patients enrolled in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial, in which hepatitis C patients who were nonresponders to prior antiviral therapy were randomized to receive maintenance pegylated interferon or placebo.

According to the trial protocol, patients were screened every 3 months for the first 3.5 years, then every 6 months thereafter on a voluntary basis, with levels of serum alpha-fetoprotein measured at each visit.

Patients who developed hepatocellular carcinoma were matched to controls without HCC in a 1:3 ratio according to the length of follow-up "in order to exclude bias caused by subjects with longer follow-up time having higher cumulative probability of HCC development, as well as more AFP values available," wrote the authors.

Overall, among 967 subjects with hepatitis C, 82 developed HCC during the study period, with a median of 18 (range, 5-22) AFP tests performed.

Dr. Lee then analyzed the association between the development of HCC and three AFP patterns.

First, the researchers assessed the rate of rise, defined as the patient’s final alpha-fetoprotein level (before study conclusion or HCC development, whichever came first) minus the AFP baseline value (on study entry), all over the follow-up duration divided by 90 days.

He found that this metric was associated with an odds ratio for developing HCC of 1.178 (P less than .001) in a simple logistic regression analysis that accounted for baseline risk factors only, with an area under the receiver-operating characteristic (AUROC) of 0.69.

Next, Dr. Lee calculated the standard deviation of AFP, defined as the standard deviation of all AFP values recorded within each patient.

In the same simple logistic regression, the standard deviation calculation was associated with an odds ratio of 1.026 for HCC per unit increase in standard deviation (P less than .001) and an AUROC of 0.76.

Third, Dr. Lee looked at the most recent AFP value on record. In this case, the odds ratio for developing HCC was 1.012 (also with P less than .001) and an AUROC of 0.76.

Finally, the researchers incorporated both standard deviation and rate of rise of AFP along with baseline age, platelet count, and smoking history to create a "history" model, which had an AUROC of 0.81 – an even better predictor than the models that looked only at one of those factors.

In an attempt to explain their findings, the researchers wrote, "it is intuitively evident why the rate of rise of AFP might be associated with risk of HCC development, but what might explain the association with standard deviation?"

They added, "The biologic basis is unknown, but we theorize that fluctuations in AFP may reflect cycles of damage and regeneration within the liver, and that growth factors involved in regeneration could stimulate hepatocarcinogenesis."

The authors acknowledged that the study had several limitations. "From a practical perspective, these metrics will only be useful once a patient has been followed for at least 2 years in order for the patterns to emerge," they wrote.

Additionally, "this study included only patients with hepatitis C; it is unknown whether these associations would be present among patients with other chronic liver diseases."

The authors said they had no relevant financial disclosures. They disclosed grant support from the National Science Foundation Graduate Research Fellowship.

*Correction, 3/25/2013: An earlier version of this story misstated the name of Clinical Gastroenterology and Hepatology.

Changes in serum alpha-fetoprotein levels over time correlated with the development of hepatocellular carcinoma in hepatitis C patients, wrote Dr. Elliot Lee and his colleagues in the April 1 issue of Clinical Gastroenterology and Hepatology.*

"If confirmed in future studies, these findings could be used to develop individualized risk assessments for clinical use, which could then influence the frequency and type of further testing" in this population, added the researchers (doi:10.1016/j.cgh.2012.11.029).

In what he called "the first large study to demonstrate that patterns of AFP [alpha-fetoprotein] over time are independently associated with HCC [hepatocellular carcinoma] development," Dr. Lee of the University of Michigan, Ann Arbor, looked at patients enrolled in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial, in which hepatitis C patients who were nonresponders to prior antiviral therapy were randomized to receive maintenance pegylated interferon or placebo.

According to the trial protocol, patients were screened every 3 months for the first 3.5 years, then every 6 months thereafter on a voluntary basis, with levels of serum alpha-fetoprotein measured at each visit.

Patients who developed hepatocellular carcinoma were matched to controls without HCC in a 1:3 ratio according to the length of follow-up "in order to exclude bias caused by subjects with longer follow-up time having higher cumulative probability of HCC development, as well as more AFP values available," wrote the authors.

Overall, among 967 subjects with hepatitis C, 82 developed HCC during the study period, with a median of 18 (range, 5-22) AFP tests performed.

Dr. Lee then analyzed the association between the development of HCC and three AFP patterns.

First, the researchers assessed the rate of rise, defined as the patient’s final alpha-fetoprotein level (before study conclusion or HCC development, whichever came first) minus the AFP baseline value (on study entry), all over the follow-up duration divided by 90 days.

He found that this metric was associated with an odds ratio for developing HCC of 1.178 (P less than .001) in a simple logistic regression analysis that accounted for baseline risk factors only, with an area under the receiver-operating characteristic (AUROC) of 0.69.

Next, Dr. Lee calculated the standard deviation of AFP, defined as the standard deviation of all AFP values recorded within each patient.

In the same simple logistic regression, the standard deviation calculation was associated with an odds ratio of 1.026 for HCC per unit increase in standard deviation (P less than .001) and an AUROC of 0.76.

Third, Dr. Lee looked at the most recent AFP value on record. In this case, the odds ratio for developing HCC was 1.012 (also with P less than .001) and an AUROC of 0.76.

Finally, the researchers incorporated both standard deviation and rate of rise of AFP along with baseline age, platelet count, and smoking history to create a "history" model, which had an AUROC of 0.81 – an even better predictor than the models that looked only at one of those factors.

In an attempt to explain their findings, the researchers wrote, "it is intuitively evident why the rate of rise of AFP might be associated with risk of HCC development, but what might explain the association with standard deviation?"

They added, "The biologic basis is unknown, but we theorize that fluctuations in AFP may reflect cycles of damage and regeneration within the liver, and that growth factors involved in regeneration could stimulate hepatocarcinogenesis."

The authors acknowledged that the study had several limitations. "From a practical perspective, these metrics will only be useful once a patient has been followed for at least 2 years in order for the patterns to emerge," they wrote.

Additionally, "this study included only patients with hepatitis C; it is unknown whether these associations would be present among patients with other chronic liver diseases."

The authors said they had no relevant financial disclosures. They disclosed grant support from the National Science Foundation Graduate Research Fellowship.

*Correction, 3/25/2013: An earlier version of this story misstated the name of Clinical Gastroenterology and Hepatology.

When analyzed as a dynamic factor over time, use of the ventilator bundle was not associated with the prevention of ventilator-associated pneumonia in a study of over 600 patients.

The finding raises doubts about the widespread use of the bundle among intensive care units and calls into question efforts to make ventilator-associated pneumonias a "never event," said lead author Dr. Martin A Croce and his associates.

"While quality improvement initiatives are extremely important in the care of critically ill and injured patients, any potential penalty for institutions that actively participate in such initiatives is unwarranted," they wrote.

Their study, appearing in the February issue of the Journal of Trauma and Acute Care Surgery, involved 630 patients at six level 1 trauma centers over a 16-month period (J. Trauma Acute Care Surg. 2013;74:354-62).

All trauma patients who were admitted to an intensive care unit and received mechanical ventilation for at least 48 hours were eligible for study inclusion (90% with blunt trauma). They were followed daily in the ICU until the development of ventilator-associated pneumonia (VAP), ICU discharge, or death.

Dr. Croce, chief of the trauma division at the University of Tennessee Health Science Center, Memphis, and colleagues assessed compliance among these patients with the Institute for Healthcare Improvement (IHI) ventilator bundle, which is a set of core measures to be assessed daily and designed to improve the outcomes of mechanical ventilation.

The four core measures assessed in this study were presence of stress ulcer prophylaxis, deep vein thrombosis prophylaxis, elevation of the head of the bed, and a daily sedation vacation with assessment of weaning.

"Oral chlorhexidine was not part of the bundle since it was added by the IHI after the study protocol was already approved," the authors wrote.

Overall, 36% of patients developed VAP (96% diagnosed with bronchoalveolar lavage), and the overall mortality was 15%.

Sixteen patients were censored from the final analysis since they developed VAP late – that is, after 16 days in the study – and the authors assumed that the efficacy of the ventilator bundle would be greatest early in an ICU stay. In the end, a total of 210 patients were available for analysis.

The investigators then looked at the impact of the ventilator bundle on VAP in two ways: by individual patient and by patient-days.

To assess individual patient compliance, the authors summed each patient’s bundle compliance score and then divided by the number of patients.

"Although this method is commonly used to calculate compliance, this method may not accurately measure bundle or component compliance because patients with either short or long stays are weighted equally," Dr. Croce and his associates said.

"Thus, equal weight is given to less severely injured patients with perfect or near-perfect compliance as is given to more severely injured patients with contraindications to some bundle components," they added.

Indeed, in this analysis, overall patient compliance with the bundle was significantly linked to a decrease in VAP.

"To avoid this bias toward short stays, compliance was also calculated by patient-days," they noted. In this method, they counted each day’s compliance as a unique event.

"Bundle compliance is a dynamic, time-dependent process during which an individual patient’s status may change from noncompliant to compliant ... depending on the patient’s condition," Dr. Croce and his associates wrote. For example, DVT prophylaxis may be held in advance of surgery and restarted again later.

In this analysis, ventilator bundle compliance was associated with neither the development nor the prevention of VAP, with a hazard ratio for bundle compliance of 1.26 (95% confidence interval, 0.845-1.877.

In fact, in this analysis, the only variable associated with VAP was male sex (hazard ratio, 1.75; 95% CI, 1.233-2.483).

"It is important that [the Centers for Medicare and Medicaid Services] and third-party payers realize that in trauma patients, VAP is closely associated with uncontrollable risk factors such as sex and injury severity and its prevention is not associated with the four components of the IHI ventilator bundle," they said.

Dr. Croce and his coinvestigators stated that the study was funded by the National Trauma Institute and the U.S. Army. They disclosed no relevant conflicts of interest.

When analyzed as a dynamic factor over time, use of the ventilator bundle was not associated with the prevention of ventilator-associated pneumonia in a study of over 600 patients.

The finding raises doubts about the widespread use of the bundle among intensive care units and calls into question efforts to make ventilator-associated pneumonias a "never event," said lead author Dr. Martin A Croce and his associates.

"While quality improvement initiatives are extremely important in the care of critically ill and injured patients, any potential penalty for institutions that actively participate in such initiatives is unwarranted," they wrote.

Their study, appearing in the February issue of the Journal of Trauma and Acute Care Surgery, involved 630 patients at six level 1 trauma centers over a 16-month period (J. Trauma Acute Care Surg. 2013;74:354-62).

All trauma patients who were admitted to an intensive care unit and received mechanical ventilation for at least 48 hours were eligible for study inclusion (90% with blunt trauma). They were followed daily in the ICU until the development of ventilator-associated pneumonia (VAP), ICU discharge, or death.

Dr. Croce, chief of the trauma division at the University of Tennessee Health Science Center, Memphis, and colleagues assessed compliance among these patients with the Institute for Healthcare Improvement (IHI) ventilator bundle, which is a set of core measures to be assessed daily and designed to improve the outcomes of mechanical ventilation.

The four core measures assessed in this study were presence of stress ulcer prophylaxis, deep vein thrombosis prophylaxis, elevation of the head of the bed, and a daily sedation vacation with assessment of weaning.

"Oral chlorhexidine was not part of the bundle since it was added by the IHI after the study protocol was already approved," the authors wrote.

Overall, 36% of patients developed VAP (96% diagnosed with bronchoalveolar lavage), and the overall mortality was 15%.

Sixteen patients were censored from the final analysis since they developed VAP late – that is, after 16 days in the study – and the authors assumed that the efficacy of the ventilator bundle would be greatest early in an ICU stay. In the end, a total of 210 patients were available for analysis.

The investigators then looked at the impact of the ventilator bundle on VAP in two ways: by individual patient and by patient-days.

To assess individual patient compliance, the authors summed each patient’s bundle compliance score and then divided by the number of patients.

"Although this method is commonly used to calculate compliance, this method may not accurately measure bundle or component compliance because patients with either short or long stays are weighted equally," Dr. Croce and his associates said.

"Thus, equal weight is given to less severely injured patients with perfect or near-perfect compliance as is given to more severely injured patients with contraindications to some bundle components," they added.

Indeed, in this analysis, overall patient compliance with the bundle was significantly linked to a decrease in VAP.

"To avoid this bias toward short stays, compliance was also calculated by patient-days," they noted. In this method, they counted each day’s compliance as a unique event.

"Bundle compliance is a dynamic, time-dependent process during which an individual patient’s status may change from noncompliant to compliant ... depending on the patient’s condition," Dr. Croce and his associates wrote. For example, DVT prophylaxis may be held in advance of surgery and restarted again later.

In this analysis, ventilator bundle compliance was associated with neither the development nor the prevention of VAP, with a hazard ratio for bundle compliance of 1.26 (95% confidence interval, 0.845-1.877.

In fact, in this analysis, the only variable associated with VAP was male sex (hazard ratio, 1.75; 95% CI, 1.233-2.483).

"It is important that [the Centers for Medicare and Medicaid Services] and third-party payers realize that in trauma patients, VAP is closely associated with uncontrollable risk factors such as sex and injury severity and its prevention is not associated with the four components of the IHI ventilator bundle," they said.

Dr. Croce and his coinvestigators stated that the study was funded by the National Trauma Institute and the U.S. Army. They disclosed no relevant conflicts of interest.

When analyzed as a dynamic factor over time, use of the ventilator bundle was not associated with the prevention of ventilator-associated pneumonia in a study of over 600 patients.

The finding raises doubts about the widespread use of the bundle among intensive care units and calls into question efforts to make ventilator-associated pneumonias a "never event," said lead author Dr. Martin A Croce and his associates.

"While quality improvement initiatives are extremely important in the care of critically ill and injured patients, any potential penalty for institutions that actively participate in such initiatives is unwarranted," they wrote.

Their study, appearing in the February issue of the Journal of Trauma and Acute Care Surgery, involved 630 patients at six level 1 trauma centers over a 16-month period (J. Trauma Acute Care Surg. 2013;74:354-62).

All trauma patients who were admitted to an intensive care unit and received mechanical ventilation for at least 48 hours were eligible for study inclusion (90% with blunt trauma). They were followed daily in the ICU until the development of ventilator-associated pneumonia (VAP), ICU discharge, or death.

Dr. Croce, chief of the trauma division at the University of Tennessee Health Science Center, Memphis, and colleagues assessed compliance among these patients with the Institute for Healthcare Improvement (IHI) ventilator bundle, which is a set of core measures to be assessed daily and designed to improve the outcomes of mechanical ventilation.

The four core measures assessed in this study were presence of stress ulcer prophylaxis, deep vein thrombosis prophylaxis, elevation of the head of the bed, and a daily sedation vacation with assessment of weaning.

"Oral chlorhexidine was not part of the bundle since it was added by the IHI after the study protocol was already approved," the authors wrote.

Overall, 36% of patients developed VAP (96% diagnosed with bronchoalveolar lavage), and the overall mortality was 15%.

Sixteen patients were censored from the final analysis since they developed VAP late – that is, after 16 days in the study – and the authors assumed that the efficacy of the ventilator bundle would be greatest early in an ICU stay. In the end, a total of 210 patients were available for analysis.

The investigators then looked at the impact of the ventilator bundle on VAP in two ways: by individual patient and by patient-days.

To assess individual patient compliance, the authors summed each patient’s bundle compliance score and then divided by the number of patients.

"Although this method is commonly used to calculate compliance, this method may not accurately measure bundle or component compliance because patients with either short or long stays are weighted equally," Dr. Croce and his associates said.

"Thus, equal weight is given to less severely injured patients with perfect or near-perfect compliance as is given to more severely injured patients with contraindications to some bundle components," they added.

Indeed, in this analysis, overall patient compliance with the bundle was significantly linked to a decrease in VAP.

"To avoid this bias toward short stays, compliance was also calculated by patient-days," they noted. In this method, they counted each day’s compliance as a unique event.

"Bundle compliance is a dynamic, time-dependent process during which an individual patient’s status may change from noncompliant to compliant ... depending on the patient’s condition," Dr. Croce and his associates wrote. For example, DVT prophylaxis may be held in advance of surgery and restarted again later.

In this analysis, ventilator bundle compliance was associated with neither the development nor the prevention of VAP, with a hazard ratio for bundle compliance of 1.26 (95% confidence interval, 0.845-1.877.

In fact, in this analysis, the only variable associated with VAP was male sex (hazard ratio, 1.75; 95% CI, 1.233-2.483).

"It is important that [the Centers for Medicare and Medicaid Services] and third-party payers realize that in trauma patients, VAP is closely associated with uncontrollable risk factors such as sex and injury severity and its prevention is not associated with the four components of the IHI ventilator bundle," they said.

Dr. Croce and his coinvestigators stated that the study was funded by the National Trauma Institute and the U.S. Army. They disclosed no relevant conflicts of interest.

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.