Denise Napoli

Therapy with a novel nonnucleoside polymerase inhibitor, in combination with a protease inhibitor and ribavirin, achieved a 100% virologic response rate at 29 days among patients with hepatitis C genotype 1, Dr. Stefan Zeuzem and colleagues reported in the December issue of Gastroenterology.

Moreover, this novel alternative to the standard peginterferon alfa regimen was safe, with no serious adverse events, and was highly tolerable, the investigators said.

"This indicates that HCV [hepatitis C virus] can be eradicated in chronically infected patients with a PegIFN-free DAA [direct-acting antiviral agent] combination regimen," the authors wrote.

Dr. Zeuzem, of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and colleagues studied 34 adult patients (mean age 51 years) who were naive to interferon, PegIFN, ribavirin, or any DAA for acute or chronic hepatitis C infection.

All patients had plasma HCV RNA levels of at least 100,000 IU/mL at screening and did not have cirrhosis.

Patients with hepatitis B virus, human immunodeficiency virus, previous or ongoing rash or photosensitivity, decompensated liver disease, or hyperbilirubinemia greater than 1.5 times the upper limit of normal were excluded.

Participants were randomized in a 1:1 fashion to receive a thrice-daily 400-mg or 600-mg dose of BI 207127, "an orally bioavailable, reversible, thumb pocket 1 nonnucleoside inhibitor (NNI) of the HCV NS5B polymerase with potent and specific antiviral activity in vitro," according to the authors (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.08.051]).

"This indicates that HCV can be eradicated in chronically infected patients with a PegIFN-free DAA combination regimen."

All participants also received BI 201335, "a second-generation HCV NS3/4A protease inhibitor with highly potent in vitro activity against GT-1a/1b subtypes," wrote the authors, at a dose of 120 mg per day, as well as daily weight-dosed ribavirin, all taken with food, for 4 weeks.

"Drug-resistance studies in cell culture demonstrate that BI 201335 and BI 207127 have different resistance profiles, and previous observations using NS3/4A protease inhibitors and NS5B thumb pocket 1 NNI compounds demonstrate that 2-drug combinations profoundly reduce the selection of drug-resistant variants," explained Dr. Zeuzem.

The researchers found that in the cohort taking the larger, 600-mg doses of the polymerase inhibitor BI 207127, virologic response rates (defined as plasma HCV RNA levels of less than 25 IU/mL) were 18%, 82%, 100%, and 100% at days 8, 15, 22, and 29, respectively.

Slightly less impressive results were seen in the 400-mg group, with rates of 27%, 47%, 67%, and 73% at days 8, 15, 22, and 29 respectively.

Also in the 400-mg cohort, "higher response rates were observed in genotype 1b infected patients, compared with genotype 1a infected patients," wrote the authors, whereas results in the 600 mg group were not contingent on sub-genotypes.

"Most patients in the 600 mg TID [three times a day] dose group even had undetectable HCV RNA at days 22 and 29 (53% and 71%, respectively), while these rates did not exceed 20% in the 400 mg TID dose group," added the investigators.

Looking at safety and tolerability, Dr. Zeuzem and colleagues noted that most patients in both dosing cohorts complained of mild diarrhea, nausea, and vomiting.

Additionally, at the 600-mg dose, 42% developed mild rashes or photosensitivities, they said, and four patients developed "transient and very mild paresthesias of very different localizations."

"However, there were no severe AEs [adverse events], serious AEs or AE-related premature treatment discontinuations within the 4-week study period."

The "crucial next step," according to the investigators, will be achievement of longer-term SVR on the novel peginterferon-free regimen.

"Moreover, eliminating not only PegIFN but also RBV [ribavirin] from future HCV treatment would undoubtedly improve tolerability and would potentially allow for the treatment of patients with RBV contraindications," they added.

Indeed, at the time of this study’s publication, a phase 2b study was ongoing.

Dr. Zeuzem, along with several of his coinvestigators, disclosed financial and consulting relationships with multiple pharmaceutical companies, including the makers of the novel drugs used in this study, Boehringer Ingelheim. Boehringer Ingelheim also funded editorial assistance provided for this article.

Therapy with a novel nonnucleoside polymerase inhibitor, in combination with a protease inhibitor and ribavirin, achieved a 100% virologic response rate at 29 days among patients with hepatitis C genotype 1, Dr. Stefan Zeuzem and colleagues reported in the December issue of Gastroenterology.

Moreover, this novel alternative to the standard peginterferon alfa regimen was safe, with no serious adverse events, and was highly tolerable, the investigators said.

"This indicates that HCV [hepatitis C virus] can be eradicated in chronically infected patients with a PegIFN-free DAA [direct-acting antiviral agent] combination regimen," the authors wrote.

Dr. Zeuzem, of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and colleagues studied 34 adult patients (mean age 51 years) who were naive to interferon, PegIFN, ribavirin, or any DAA for acute or chronic hepatitis C infection.

All patients had plasma HCV RNA levels of at least 100,000 IU/mL at screening and did not have cirrhosis.

Patients with hepatitis B virus, human immunodeficiency virus, previous or ongoing rash or photosensitivity, decompensated liver disease, or hyperbilirubinemia greater than 1.5 times the upper limit of normal were excluded.

Participants were randomized in a 1:1 fashion to receive a thrice-daily 400-mg or 600-mg dose of BI 207127, "an orally bioavailable, reversible, thumb pocket 1 nonnucleoside inhibitor (NNI) of the HCV NS5B polymerase with potent and specific antiviral activity in vitro," according to the authors (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.08.051]).

"This indicates that HCV can be eradicated in chronically infected patients with a PegIFN-free DAA combination regimen."

All participants also received BI 201335, "a second-generation HCV NS3/4A protease inhibitor with highly potent in vitro activity against GT-1a/1b subtypes," wrote the authors, at a dose of 120 mg per day, as well as daily weight-dosed ribavirin, all taken with food, for 4 weeks.

"Drug-resistance studies in cell culture demonstrate that BI 201335 and BI 207127 have different resistance profiles, and previous observations using NS3/4A protease inhibitors and NS5B thumb pocket 1 NNI compounds demonstrate that 2-drug combinations profoundly reduce the selection of drug-resistant variants," explained Dr. Zeuzem.

The researchers found that in the cohort taking the larger, 600-mg doses of the polymerase inhibitor BI 207127, virologic response rates (defined as plasma HCV RNA levels of less than 25 IU/mL) were 18%, 82%, 100%, and 100% at days 8, 15, 22, and 29, respectively.

Slightly less impressive results were seen in the 400-mg group, with rates of 27%, 47%, 67%, and 73% at days 8, 15, 22, and 29 respectively.

Also in the 400-mg cohort, "higher response rates were observed in genotype 1b infected patients, compared with genotype 1a infected patients," wrote the authors, whereas results in the 600 mg group were not contingent on sub-genotypes.

"Most patients in the 600 mg TID [three times a day] dose group even had undetectable HCV RNA at days 22 and 29 (53% and 71%, respectively), while these rates did not exceed 20% in the 400 mg TID dose group," added the investigators.

Looking at safety and tolerability, Dr. Zeuzem and colleagues noted that most patients in both dosing cohorts complained of mild diarrhea, nausea, and vomiting.

Additionally, at the 600-mg dose, 42% developed mild rashes or photosensitivities, they said, and four patients developed "transient and very mild paresthesias of very different localizations."

"However, there were no severe AEs [adverse events], serious AEs or AE-related premature treatment discontinuations within the 4-week study period."

The "crucial next step," according to the investigators, will be achievement of longer-term SVR on the novel peginterferon-free regimen.

"Moreover, eliminating not only PegIFN but also RBV [ribavirin] from future HCV treatment would undoubtedly improve tolerability and would potentially allow for the treatment of patients with RBV contraindications," they added.

Indeed, at the time of this study’s publication, a phase 2b study was ongoing.

Dr. Zeuzem, along with several of his coinvestigators, disclosed financial and consulting relationships with multiple pharmaceutical companies, including the makers of the novel drugs used in this study, Boehringer Ingelheim. Boehringer Ingelheim also funded editorial assistance provided for this article.

Therapy with a novel nonnucleoside polymerase inhibitor, in combination with a protease inhibitor and ribavirin, achieved a 100% virologic response rate at 29 days among patients with hepatitis C genotype 1, Dr. Stefan Zeuzem and colleagues reported in the December issue of Gastroenterology.

Moreover, this novel alternative to the standard peginterferon alfa regimen was safe, with no serious adverse events, and was highly tolerable, the investigators said.

"This indicates that HCV [hepatitis C virus] can be eradicated in chronically infected patients with a PegIFN-free DAA [direct-acting antiviral agent] combination regimen," the authors wrote.

Dr. Zeuzem, of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and colleagues studied 34 adult patients (mean age 51 years) who were naive to interferon, PegIFN, ribavirin, or any DAA for acute or chronic hepatitis C infection.

All patients had plasma HCV RNA levels of at least 100,000 IU/mL at screening and did not have cirrhosis.

Patients with hepatitis B virus, human immunodeficiency virus, previous or ongoing rash or photosensitivity, decompensated liver disease, or hyperbilirubinemia greater than 1.5 times the upper limit of normal were excluded.

Participants were randomized in a 1:1 fashion to receive a thrice-daily 400-mg or 600-mg dose of BI 207127, "an orally bioavailable, reversible, thumb pocket 1 nonnucleoside inhibitor (NNI) of the HCV NS5B polymerase with potent and specific antiviral activity in vitro," according to the authors (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.08.051]).

"This indicates that HCV can be eradicated in chronically infected patients with a PegIFN-free DAA combination regimen."

All participants also received BI 201335, "a second-generation HCV NS3/4A protease inhibitor with highly potent in vitro activity against GT-1a/1b subtypes," wrote the authors, at a dose of 120 mg per day, as well as daily weight-dosed ribavirin, all taken with food, for 4 weeks.

"Drug-resistance studies in cell culture demonstrate that BI 201335 and BI 207127 have different resistance profiles, and previous observations using NS3/4A protease inhibitors and NS5B thumb pocket 1 NNI compounds demonstrate that 2-drug combinations profoundly reduce the selection of drug-resistant variants," explained Dr. Zeuzem.

The researchers found that in the cohort taking the larger, 600-mg doses of the polymerase inhibitor BI 207127, virologic response rates (defined as plasma HCV RNA levels of less than 25 IU/mL) were 18%, 82%, 100%, and 100% at days 8, 15, 22, and 29, respectively.

Slightly less impressive results were seen in the 400-mg group, with rates of 27%, 47%, 67%, and 73% at days 8, 15, 22, and 29 respectively.

Also in the 400-mg cohort, "higher response rates were observed in genotype 1b infected patients, compared with genotype 1a infected patients," wrote the authors, whereas results in the 600 mg group were not contingent on sub-genotypes.

"Most patients in the 600 mg TID [three times a day] dose group even had undetectable HCV RNA at days 22 and 29 (53% and 71%, respectively), while these rates did not exceed 20% in the 400 mg TID dose group," added the investigators.

Looking at safety and tolerability, Dr. Zeuzem and colleagues noted that most patients in both dosing cohorts complained of mild diarrhea, nausea, and vomiting.

Additionally, at the 600-mg dose, 42% developed mild rashes or photosensitivities, they said, and four patients developed "transient and very mild paresthesias of very different localizations."

"However, there were no severe AEs [adverse events], serious AEs or AE-related premature treatment discontinuations within the 4-week study period."

The "crucial next step," according to the investigators, will be achievement of longer-term SVR on the novel peginterferon-free regimen.

"Moreover, eliminating not only PegIFN but also RBV [ribavirin] from future HCV treatment would undoubtedly improve tolerability and would potentially allow for the treatment of patients with RBV contraindications," they added.

Indeed, at the time of this study’s publication, a phase 2b study was ongoing.

Dr. Zeuzem, along with several of his coinvestigators, disclosed financial and consulting relationships with multiple pharmaceutical companies, including the makers of the novel drugs used in this study, Boehringer Ingelheim. Boehringer Ingelheim also funded editorial assistance provided for this article.

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.

During unsedated colonoscopy, fewer patients receiving water infusion for cecal intubation requested pain medication, compared with patients receiving air insufflation, reported Dr. Jürgen Pohl and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

Dr. Pohl of the University of Mainz (Germany) and colleagues studied 116 consecutive outpatients presenting for screening, surveillance, or diagnostic colonoscopy who elected not to receive preprocedure sedation.

Patients were subsequently randomized to receive either standard air insufflation of the colon when needed, or water infusion, whereby warm water (37° C) was used exclusively to distend the colon and the air supply was turned off until the cecum was reached.

"If sufficient visualization of colonic lumen could not be achieved with water infusion within 5 minutes, and the endoscopist judged it risky to advance the colonoscope further, the water pump was switched off and the procedure was completed with air," wrote the authors (Clin. Gastroenterol. Hepatol. 2011 July 11 [doi:10.1016/j.cgh.2011.06.031]). These cases were recorded as failures.

Throughout the procedure, patient discomfort and desire for sedation and/or analgesia were assessed in both groups at intervals of 2-3 minutes on a scale of 0-10, with higher numbers signifying worse pain.

Overall, 104 of 116 colonoscopies (89.7%) were completed to the cecum. "During colonoscope insertion in the water group, significantly fewer patients requested sedation (8.6% vs. 34.5% in the air group; P = .003)," they wrote.

The water group’s average maximum pain scores were lower, too (2.8 vs. 4.2 in the air group; P = .02), and less sedation and/or analgesia was administered to the water cohort (P = .02).

However, the authors also pointed out that the rate of complete cecal intubation was significantly lower among water-infusion patients, compared with the air group (82.8% vs. 96.5%, respectively; P = .03), with 10 procedures considered failures in the water group.

These 10 failures, explained Dr. Pohl, occurred when "residual stool [that was] mixed with infused water impaired visibility to an extent that made safe advancement impossible in difficult segments." The procedures were subsequently completed after suction and air insufflation, he added.

There were no significant differences with regard to the proportion of patients requiring abdominal compression or a position change during insertion of the endoscope. "Nor were any significant differences observed between the two groups with regard to recovery times," added Dr. Pohl and colleagues.

The researchers postulated that the success rate of water infusion "might be improved if moderate insufflation of air were to be applied as needed to enhance visualization in case of difficult areas and/or impaired viewing due to suspended residual fecal matter."

They added, "However, longer procedure times with water infusion colonoscopy remain a major problem, given the absolute necessity of time efficiency in a demanding reimbursement environment."

The authors disclosed that this study was supported by Fujinon Inc., maker of colonoscopes and other devices. They declared no individual conflicts.

During unsedated colonoscopy, fewer patients receiving water infusion for cecal intubation requested pain medication, compared with patients receiving air insufflation, reported Dr. Jürgen Pohl and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

Dr. Pohl of the University of Mainz (Germany) and colleagues studied 116 consecutive outpatients presenting for screening, surveillance, or diagnostic colonoscopy who elected not to receive preprocedure sedation.

Patients were subsequently randomized to receive either standard air insufflation of the colon when needed, or water infusion, whereby warm water (37° C) was used exclusively to distend the colon and the air supply was turned off until the cecum was reached.

"If sufficient visualization of colonic lumen could not be achieved with water infusion within 5 minutes, and the endoscopist judged it risky to advance the colonoscope further, the water pump was switched off and the procedure was completed with air," wrote the authors (Clin. Gastroenterol. Hepatol. 2011 July 11 [doi:10.1016/j.cgh.2011.06.031]). These cases were recorded as failures.

Throughout the procedure, patient discomfort and desire for sedation and/or analgesia were assessed in both groups at intervals of 2-3 minutes on a scale of 0-10, with higher numbers signifying worse pain.

Overall, 104 of 116 colonoscopies (89.7%) were completed to the cecum. "During colonoscope insertion in the water group, significantly fewer patients requested sedation (8.6% vs. 34.5% in the air group; P = .003)," they wrote.

The water group’s average maximum pain scores were lower, too (2.8 vs. 4.2 in the air group; P = .02), and less sedation and/or analgesia was administered to the water cohort (P = .02).

However, the authors also pointed out that the rate of complete cecal intubation was significantly lower among water-infusion patients, compared with the air group (82.8% vs. 96.5%, respectively; P = .03), with 10 procedures considered failures in the water group.

These 10 failures, explained Dr. Pohl, occurred when "residual stool [that was] mixed with infused water impaired visibility to an extent that made safe advancement impossible in difficult segments." The procedures were subsequently completed after suction and air insufflation, he added.

There were no significant differences with regard to the proportion of patients requiring abdominal compression or a position change during insertion of the endoscope. "Nor were any significant differences observed between the two groups with regard to recovery times," added Dr. Pohl and colleagues.

The researchers postulated that the success rate of water infusion "might be improved if moderate insufflation of air were to be applied as needed to enhance visualization in case of difficult areas and/or impaired viewing due to suspended residual fecal matter."

They added, "However, longer procedure times with water infusion colonoscopy remain a major problem, given the absolute necessity of time efficiency in a demanding reimbursement environment."

The authors disclosed that this study was supported by Fujinon Inc., maker of colonoscopes and other devices. They declared no individual conflicts.

During unsedated colonoscopy, fewer patients receiving water infusion for cecal intubation requested pain medication, compared with patients receiving air insufflation, reported Dr. Jürgen Pohl and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

Dr. Pohl of the University of Mainz (Germany) and colleagues studied 116 consecutive outpatients presenting for screening, surveillance, or diagnostic colonoscopy who elected not to receive preprocedure sedation.

Patients were subsequently randomized to receive either standard air insufflation of the colon when needed, or water infusion, whereby warm water (37° C) was used exclusively to distend the colon and the air supply was turned off until the cecum was reached.

"If sufficient visualization of colonic lumen could not be achieved with water infusion within 5 minutes, and the endoscopist judged it risky to advance the colonoscope further, the water pump was switched off and the procedure was completed with air," wrote the authors (Clin. Gastroenterol. Hepatol. 2011 July 11 [doi:10.1016/j.cgh.2011.06.031]). These cases were recorded as failures.

Throughout the procedure, patient discomfort and desire for sedation and/or analgesia were assessed in both groups at intervals of 2-3 minutes on a scale of 0-10, with higher numbers signifying worse pain.

Overall, 104 of 116 colonoscopies (89.7%) were completed to the cecum. "During colonoscope insertion in the water group, significantly fewer patients requested sedation (8.6% vs. 34.5% in the air group; P = .003)," they wrote.

The water group’s average maximum pain scores were lower, too (2.8 vs. 4.2 in the air group; P = .02), and less sedation and/or analgesia was administered to the water cohort (P = .02).

However, the authors also pointed out that the rate of complete cecal intubation was significantly lower among water-infusion patients, compared with the air group (82.8% vs. 96.5%, respectively; P = .03), with 10 procedures considered failures in the water group.

These 10 failures, explained Dr. Pohl, occurred when "residual stool [that was] mixed with infused water impaired visibility to an extent that made safe advancement impossible in difficult segments." The procedures were subsequently completed after suction and air insufflation, he added.

There were no significant differences with regard to the proportion of patients requiring abdominal compression or a position change during insertion of the endoscope. "Nor were any significant differences observed between the two groups with regard to recovery times," added Dr. Pohl and colleagues.

The researchers postulated that the success rate of water infusion "might be improved if moderate insufflation of air were to be applied as needed to enhance visualization in case of difficult areas and/or impaired viewing due to suspended residual fecal matter."

They added, "However, longer procedure times with water infusion colonoscopy remain a major problem, given the absolute necessity of time efficiency in a demanding reimbursement environment."

The authors disclosed that this study was supported by Fujinon Inc., maker of colonoscopes and other devices. They declared no individual conflicts.

One in six newly diagnosed pediatric systemic lupus erythematosus patients were found to have low bone mineral density, a study has shown.

The single-cohort study of 80 children and adolescents with newly diagnosed SLE also found that steroid exposure was not significantly linked to decreased BMD.

The findings suggest that "the detrimental effect of systemic inflammation on BMD is more important than short term exposure to corticosteroids even at high dose," noted Dr. Siok Hoon Lily Lim and colleagues (Ann. Rheum. Dis. 2011;70:1991-4).

Dr. Lim of the department of pediatrics, division of rheumatology, at the University of Toronto, included patients in the study if they were between 5 and 18 years of age. All were seen at the Hospital for Sick Kids, also in Toronto, between December 2001 and December 2007. The patients underwent a dual-energy x-ray absorptiometry (DXA) scan within 3 months of SLE diagnosis.

Low lumbar spine (LS) BMD was defined as a z score of less than or equal to –2.0, in line with recommendations from the International Society of Clinical Densitometry and the American Academy of Pediatrics. In addition, a hip BMD of less than 80% was defined as low.

Overall, the median age at SLE diagnosis was 14.2 years (range, 5.0-17.7 years). The mean lumbar spine BMD z score for the cohort was –0.4 (range, –3.3 to 3.2); mean body mass index was 19.8 kg/m².

The researchers found that at the time of the DXA scan, 12 patients (15%) had overall low BMD, defined as low lumbar spine BMD with or without low hip BMD.

One-third (26 patients) were also found to have "abnormal" BMD, defined as a lumbar spine BMD less than or equal to –1.0, with or without low hip BMD.

Meanwhile, in terms of steroid use, 22 patients were steroid naive at the time of the DXA scan, noted the researchers. "There was no difference in LS (P = 0.63) or hip (P = 0.89) BMD, irrespective of exposure to steroids," among the cohort.

"Steroid-exposed patients were not more likely to have low (LS/hip) BMD (P = 0.23)," the investigators added. The only factors that were significantly linked to low lumbar spine BMD were a low BMI (P less than 0.0001) and low corrected serum calcium (P = 0.0036).

For every standard deviation decrease in the BMI z score, the odds of having low BMD further increased by 65% (odds ratio, 0.35), Dr Lim and colleagues reported.

They said that the study was limited by a lack of information regarding patients’ genetic risk factors for low BMD. They were also unable to account for premorbid activity levels, including weight-bearing activity, which is thought to impact bone mass accrual, although this effect would likely be less pronounced in patients with lower-limb arthritis, they noted.

Nevertheless, "we recommend that all newly diagnosed patients with [pediatric] SLE should have a baseline BMD, especially in patients with risk factors identified in this study," including a low BMI, concluded the researchers. "Longitudinal follow-up of this cohort of patients will clarify their future outcomes."

The investigators reported having no relevant financial disclosures.

One in six newly diagnosed pediatric systemic lupus erythematosus patients were found to have low bone mineral density, a study has shown.

The single-cohort study of 80 children and adolescents with newly diagnosed SLE also found that steroid exposure was not significantly linked to decreased BMD.

The findings suggest that "the detrimental effect of systemic inflammation on BMD is more important than short term exposure to corticosteroids even at high dose," noted Dr. Siok Hoon Lily Lim and colleagues (Ann. Rheum. Dis. 2011;70:1991-4).

Dr. Lim of the department of pediatrics, division of rheumatology, at the University of Toronto, included patients in the study if they were between 5 and 18 years of age. All were seen at the Hospital for Sick Kids, also in Toronto, between December 2001 and December 2007. The patients underwent a dual-energy x-ray absorptiometry (DXA) scan within 3 months of SLE diagnosis.

Low lumbar spine (LS) BMD was defined as a z score of less than or equal to –2.0, in line with recommendations from the International Society of Clinical Densitometry and the American Academy of Pediatrics. In addition, a hip BMD of less than 80% was defined as low.

Overall, the median age at SLE diagnosis was 14.2 years (range, 5.0-17.7 years). The mean lumbar spine BMD z score for the cohort was –0.4 (range, –3.3 to 3.2); mean body mass index was 19.8 kg/m².

The researchers found that at the time of the DXA scan, 12 patients (15%) had overall low BMD, defined as low lumbar spine BMD with or without low hip BMD.

One-third (26 patients) were also found to have "abnormal" BMD, defined as a lumbar spine BMD less than or equal to –1.0, with or without low hip BMD.

Meanwhile, in terms of steroid use, 22 patients were steroid naive at the time of the DXA scan, noted the researchers. "There was no difference in LS (P = 0.63) or hip (P = 0.89) BMD, irrespective of exposure to steroids," among the cohort.

"Steroid-exposed patients were not more likely to have low (LS/hip) BMD (P = 0.23)," the investigators added. The only factors that were significantly linked to low lumbar spine BMD were a low BMI (P less than 0.0001) and low corrected serum calcium (P = 0.0036).

For every standard deviation decrease in the BMI z score, the odds of having low BMD further increased by 65% (odds ratio, 0.35), Dr Lim and colleagues reported.

They said that the study was limited by a lack of information regarding patients’ genetic risk factors for low BMD. They were also unable to account for premorbid activity levels, including weight-bearing activity, which is thought to impact bone mass accrual, although this effect would likely be less pronounced in patients with lower-limb arthritis, they noted.

Nevertheless, "we recommend that all newly diagnosed patients with [pediatric] SLE should have a baseline BMD, especially in patients with risk factors identified in this study," including a low BMI, concluded the researchers. "Longitudinal follow-up of this cohort of patients will clarify their future outcomes."

The investigators reported having no relevant financial disclosures.

One in six newly diagnosed pediatric systemic lupus erythematosus patients were found to have low bone mineral density, a study has shown.

The single-cohort study of 80 children and adolescents with newly diagnosed SLE also found that steroid exposure was not significantly linked to decreased BMD.

The findings suggest that "the detrimental effect of systemic inflammation on BMD is more important than short term exposure to corticosteroids even at high dose," noted Dr. Siok Hoon Lily Lim and colleagues (Ann. Rheum. Dis. 2011;70:1991-4).

Dr. Lim of the department of pediatrics, division of rheumatology, at the University of Toronto, included patients in the study if they were between 5 and 18 years of age. All were seen at the Hospital for Sick Kids, also in Toronto, between December 2001 and December 2007. The patients underwent a dual-energy x-ray absorptiometry (DXA) scan within 3 months of SLE diagnosis.

Low lumbar spine (LS) BMD was defined as a z score of less than or equal to –2.0, in line with recommendations from the International Society of Clinical Densitometry and the American Academy of Pediatrics. In addition, a hip BMD of less than 80% was defined as low.

Overall, the median age at SLE diagnosis was 14.2 years (range, 5.0-17.7 years). The mean lumbar spine BMD z score for the cohort was –0.4 (range, –3.3 to 3.2); mean body mass index was 19.8 kg/m².

The researchers found that at the time of the DXA scan, 12 patients (15%) had overall low BMD, defined as low lumbar spine BMD with or without low hip BMD.

One-third (26 patients) were also found to have "abnormal" BMD, defined as a lumbar spine BMD less than or equal to –1.0, with or without low hip BMD.

Meanwhile, in terms of steroid use, 22 patients were steroid naive at the time of the DXA scan, noted the researchers. "There was no difference in LS (P = 0.63) or hip (P = 0.89) BMD, irrespective of exposure to steroids," among the cohort.

"Steroid-exposed patients were not more likely to have low (LS/hip) BMD (P = 0.23)," the investigators added. The only factors that were significantly linked to low lumbar spine BMD were a low BMI (P less than 0.0001) and low corrected serum calcium (P = 0.0036).

For every standard deviation decrease in the BMI z score, the odds of having low BMD further increased by 65% (odds ratio, 0.35), Dr Lim and colleagues reported.

They said that the study was limited by a lack of information regarding patients’ genetic risk factors for low BMD. They were also unable to account for premorbid activity levels, including weight-bearing activity, which is thought to impact bone mass accrual, although this effect would likely be less pronounced in patients with lower-limb arthritis, they noted.

Nevertheless, "we recommend that all newly diagnosed patients with [pediatric] SLE should have a baseline BMD, especially in patients with risk factors identified in this study," including a low BMI, concluded the researchers. "Longitudinal follow-up of this cohort of patients will clarify their future outcomes."

The investigators reported having no relevant financial disclosures.

Disability in rheumatoid arthritis has declined an average of 1.7% per year since the advent of disease-modifying antirheumatic drugs, especially methotrexate.

The finding justifies "continued emphasis on early and consistent [disease-modifying antirheumatic drugs (DMARDs)] use and the incorporation of biologicals into our therapeutic repertoire," wrote Dr. Eswar Krishnan in Annals of the Rheumatic Diseases, published online Sept. 27 (doi:10.1136/annrheumdis-2011-200354).

Dr. Krishnan of the division of rheumatology and immunology at Stanford (Calif.) University and his colleagues looked at 4,651 adult patients from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), a national longitudinal database. Most (76%) were female, and nearly all (88%) were white.

All patients were mailed a health assessment questionnaire (HAQ) at 6-month intervals, beginning in 1983 through 2006, which assessed disability on a scale of 0-3, with 3 being the worst, in eight areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. An average overall score was obtained for each patient by summing all scores and dividing by 8.

Overall, a mean of 13 semiannual assessments were completed during the study period per patient.

Dr. Krishnan found that the average HAQ-disability score improved from 1.3 in the 1980s, to 1.2 in the 1990s, to 1.1 or lower in the 2000s.

The authors then divided up the study period into three defined eras. The first, from 1982 to 1990, represented the "NSAID-based" era, when nonsteroidal anti-inflammatory drug treatment was the primary therapy for RA. The second era, from 1991 to 2000, they called the "methotrexate/DMARD" era, when these agents dominated treatments.

The final period, from 2001 to 2006, was deemed the "methotrexate and biologic DMARD period," when combination therapy with biologic and nonbiologic agents became the norm.

When thus divided and plotted on a graph using least-squares regression, wrote the authors, the trend lines showed that disability remained relatively constant over the NSAID-based era (prior to 1990), then declined significantly (P = .001) in the nonbiologic (methotrexate) era (1992-1997) and in the biologic and nonbiologic era (P less than .01).

Moreover, wrote the authors, "the composition of our cohort changed over time in a way that can [be] expected to increase disability over time," including an increasing average age (57.2 years in 1983, vs. 64.3 years in 2006) and disease duration (a mean of 14.4 years at cohort inception to 24.1 years in 200).

"Thus, the estimated declines in RA disability in the biological era are likely to be an underestimate of the true declines," they added.

"Our finding supports the prevailing notion that ‘tight inflammation control’ is a desirable therapeutic strategy," they concluded.

Dr. Krishnan postulated that changing drug therapies were not the only contributors to decreasing disability over time.

For one, smoking prevalence declined from a high of 27.9% to just 5% among the study participants between 1992 and 2006, reported the authors.

"Another relevant trend has been the setting of more stringent targets for RA treatment success, such as ‘remission’ or ‘low disease activity,’ which perhaps leads to an earlier escalation to more aggressive treatment regimes," they added.

Finally, the authors pointed out that an "ongoing national secular decline in disability" may have resulted in a decrease of comorbid heart disease, chronic obstructive pulmonary disease, and stroke, conditions that could exacerbate disability in this population.

The authors disclosed that Centocor Ortho-Biotech, a maker of biologic RA drugs, funded the study. They disclosed no additional individual competing interests.

Disability in rheumatoid arthritis has declined an average of 1.7% per year since the advent of disease-modifying antirheumatic drugs, especially methotrexate.

The finding justifies "continued emphasis on early and consistent [disease-modifying antirheumatic drugs (DMARDs)] use and the incorporation of biologicals into our therapeutic repertoire," wrote Dr. Eswar Krishnan in Annals of the Rheumatic Diseases, published online Sept. 27 (doi:10.1136/annrheumdis-2011-200354).

Dr. Krishnan of the division of rheumatology and immunology at Stanford (Calif.) University and his colleagues looked at 4,651 adult patients from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), a national longitudinal database. Most (76%) were female, and nearly all (88%) were white.

All patients were mailed a health assessment questionnaire (HAQ) at 6-month intervals, beginning in 1983 through 2006, which assessed disability on a scale of 0-3, with 3 being the worst, in eight areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. An average overall score was obtained for each patient by summing all scores and dividing by 8.

Overall, a mean of 13 semiannual assessments were completed during the study period per patient.

Dr. Krishnan found that the average HAQ-disability score improved from 1.3 in the 1980s, to 1.2 in the 1990s, to 1.1 or lower in the 2000s.

The authors then divided up the study period into three defined eras. The first, from 1982 to 1990, represented the "NSAID-based" era, when nonsteroidal anti-inflammatory drug treatment was the primary therapy for RA. The second era, from 1991 to 2000, they called the "methotrexate/DMARD" era, when these agents dominated treatments.

The final period, from 2001 to 2006, was deemed the "methotrexate and biologic DMARD period," when combination therapy with biologic and nonbiologic agents became the norm.

When thus divided and plotted on a graph using least-squares regression, wrote the authors, the trend lines showed that disability remained relatively constant over the NSAID-based era (prior to 1990), then declined significantly (P = .001) in the nonbiologic (methotrexate) era (1992-1997) and in the biologic and nonbiologic era (P less than .01).

Moreover, wrote the authors, "the composition of our cohort changed over time in a way that can [be] expected to increase disability over time," including an increasing average age (57.2 years in 1983, vs. 64.3 years in 2006) and disease duration (a mean of 14.4 years at cohort inception to 24.1 years in 200).

"Thus, the estimated declines in RA disability in the biological era are likely to be an underestimate of the true declines," they added.

"Our finding supports the prevailing notion that ‘tight inflammation control’ is a desirable therapeutic strategy," they concluded.

Dr. Krishnan postulated that changing drug therapies were not the only contributors to decreasing disability over time.

For one, smoking prevalence declined from a high of 27.9% to just 5% among the study participants between 1992 and 2006, reported the authors.

"Another relevant trend has been the setting of more stringent targets for RA treatment success, such as ‘remission’ or ‘low disease activity,’ which perhaps leads to an earlier escalation to more aggressive treatment regimes," they added.

Finally, the authors pointed out that an "ongoing national secular decline in disability" may have resulted in a decrease of comorbid heart disease, chronic obstructive pulmonary disease, and stroke, conditions that could exacerbate disability in this population.

The authors disclosed that Centocor Ortho-Biotech, a maker of biologic RA drugs, funded the study. They disclosed no additional individual competing interests.

Disability in rheumatoid arthritis has declined an average of 1.7% per year since the advent of disease-modifying antirheumatic drugs, especially methotrexate.

The finding justifies "continued emphasis on early and consistent [disease-modifying antirheumatic drugs (DMARDs)] use and the incorporation of biologicals into our therapeutic repertoire," wrote Dr. Eswar Krishnan in Annals of the Rheumatic Diseases, published online Sept. 27 (doi:10.1136/annrheumdis-2011-200354).

Dr. Krishnan of the division of rheumatology and immunology at Stanford (Calif.) University and his colleagues looked at 4,651 adult patients from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), a national longitudinal database. Most (76%) were female, and nearly all (88%) were white.

All patients were mailed a health assessment questionnaire (HAQ) at 6-month intervals, beginning in 1983 through 2006, which assessed disability on a scale of 0-3, with 3 being the worst, in eight areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. An average overall score was obtained for each patient by summing all scores and dividing by 8.

Overall, a mean of 13 semiannual assessments were completed during the study period per patient.

Dr. Krishnan found that the average HAQ-disability score improved from 1.3 in the 1980s, to 1.2 in the 1990s, to 1.1 or lower in the 2000s.

The authors then divided up the study period into three defined eras. The first, from 1982 to 1990, represented the "NSAID-based" era, when nonsteroidal anti-inflammatory drug treatment was the primary therapy for RA. The second era, from 1991 to 2000, they called the "methotrexate/DMARD" era, when these agents dominated treatments.

The final period, from 2001 to 2006, was deemed the "methotrexate and biologic DMARD period," when combination therapy with biologic and nonbiologic agents became the norm.

When thus divided and plotted on a graph using least-squares regression, wrote the authors, the trend lines showed that disability remained relatively constant over the NSAID-based era (prior to 1990), then declined significantly (P = .001) in the nonbiologic (methotrexate) era (1992-1997) and in the biologic and nonbiologic era (P less than .01).

Moreover, wrote the authors, "the composition of our cohort changed over time in a way that can [be] expected to increase disability over time," including an increasing average age (57.2 years in 1983, vs. 64.3 years in 2006) and disease duration (a mean of 14.4 years at cohort inception to 24.1 years in 200).

"Thus, the estimated declines in RA disability in the biological era are likely to be an underestimate of the true declines," they added.

"Our finding supports the prevailing notion that ‘tight inflammation control’ is a desirable therapeutic strategy," they concluded.

Dr. Krishnan postulated that changing drug therapies were not the only contributors to decreasing disability over time.

For one, smoking prevalence declined from a high of 27.9% to just 5% among the study participants between 1992 and 2006, reported the authors.

"Another relevant trend has been the setting of more stringent targets for RA treatment success, such as ‘remission’ or ‘low disease activity,’ which perhaps leads to an earlier escalation to more aggressive treatment regimes," they added.

Finally, the authors pointed out that an "ongoing national secular decline in disability" may have resulted in a decrease of comorbid heart disease, chronic obstructive pulmonary disease, and stroke, conditions that could exacerbate disability in this population.

The authors disclosed that Centocor Ortho-Biotech, a maker of biologic RA drugs, funded the study. They disclosed no additional individual competing interests.

Use of disease-modifying antirheumatic drugs like methotrexate, sulfasalazine, and leflunomide may improve the outcome of severe psoriatic arthritis if they are given earlier in the course of the disease.

That is one of the recommendations from a new set of guidelines on the treatment of psoriatic arthritis (PsA), issued by a European League Against Rheumatism (EULAR) task force and published online Sept. 27 in Annals of the Rheumatic Diseases.

According to Dr. Laure Gossec, lead author of the report, the recommendations from 28 rheumatologists, 2 patients, an infectious disease specialist, a dermatologist, a physiotherapist, and 2 rheumatology fellows are meant to offer some guidance for what is often a "clinically heterogeneous" disease with few available high-quality studies.

"The treatment of psoriatic arthritis has changed dramatically over recent years, despite the lack of sufficient knowledge on etiology and detailed pathogenesis," wrote Dr. Gossec of Paris Descartes University and colleagues (Ann. Rheum. Dis. 2011 [doi:10.1136/annrheumdis-2011-200350]).

And although the new guidelines "reflect the current state of evidence and thought in the area of PsA management, ... several of the recommendations are strongly based on expert opinion, which in turn is based on clinical practice that has emerged in certain institutions, rather than available evidence," wrote the authors. "This is due to the paucity of data in the field of PsA."

The first recommendation, agreed upon unanimously by the task force, is that "in the vast majority of PsA patients, NSAIDs [nonsteroidal anti-inflammatory drugs] should be used as first-line treatment, although the data regarding the usefulness of NSAIDs in PsA are limited."

The task force conceded that in the setting of cardiovascular or gastrointestinal disease, these drugs, including cyclooxygenase-2 inhibitors – which data suggest are as effective as nonselective NSAIDs for PsA – may not be appropriate.

A second recommendation concerned the "early" use of disease-modifying antirheumatic drugs (DMARDs), specifically within 1 year of diagnosis for patients with active disease (i.e., one or more inflamed/tender joints) whose symptoms are unrelieved by NSAIDs.

However, "regarding the choice of a DMARD, here again there are few data and almost no head-to-head comparisons," wrote the authors.

Nevertheless, "the experts recommended methotrexate as the first-choice DMARD ... based in particular on broad therapeutic dose ranges, different application forms [oral or subcutaneous preparations], and available data in PsA and in other inflammatory diseases."

"In the vast majority of PsA patients, NSAIDs should be used as first-line treatment."

"Transaminase enzymes should be carefully monitored in patients with PsA who receive treatment with methotrexate or leflunomide," especially in the setting of comorbid alcohol abuse, diabetes, or statin therapy, they added.

The authors also weighed in on the use of steroids, especially in localized disease. "Intra-articular steroids are efficacious for mono/oligoarthritis or single joint flares in otherwise well-controlled polyarthritis," they wrote. Systemic steroid use, however, should be undertaken with caution, in light of case reports of skin flares that occur at the time of tapering. And when doses are being tapered, "attention should be paid to the potential worsening of skin disease (rebound)," they added.

Finally, the group addressed the use of tumor necrosis factor inhibitors, which can be considered in the event of "treatment failure," defined as an inability to reach target low disease activity after 3-6 months of treatment. In a very few patients, TNF inhibitors may be considered as a first-line treatment in DMARD-naive patients with very active disease. This recommendation is based entirely on expert opinion; there are no data to support it.

"TNF inhibitors (adalimumab, etanercept, golimumab, and infliximab) have demonstrated efficacy in PsA, both for skin and joint involvement, as well as in preventing radiographic damage," wrote the authors.

They added: "This information may be taken into consideration for the choice of TNF inhibitors in patients with clinically significant skin involvement."

The development of the recommendations was sponsored by EULAR. Several of the authors of this article disclosed financial relationships to numerous pharmaceutical companies and the makers of drugs used in PsA treatment.

Use of disease-modifying antirheumatic drugs like methotrexate, sulfasalazine, and leflunomide may improve the outcome of severe psoriatic arthritis if they are given earlier in the course of the disease.

That is one of the recommendations from a new set of guidelines on the treatment of psoriatic arthritis (PsA), issued by a European League Against Rheumatism (EULAR) task force and published online Sept. 27 in Annals of the Rheumatic Diseases.

According to Dr. Laure Gossec, lead author of the report, the recommendations from 28 rheumatologists, 2 patients, an infectious disease specialist, a dermatologist, a physiotherapist, and 2 rheumatology fellows are meant to offer some guidance for what is often a "clinically heterogeneous" disease with few available high-quality studies.

"The treatment of psoriatic arthritis has changed dramatically over recent years, despite the lack of sufficient knowledge on etiology and detailed pathogenesis," wrote Dr. Gossec of Paris Descartes University and colleagues (Ann. Rheum. Dis. 2011 [doi:10.1136/annrheumdis-2011-200350]).

And although the new guidelines "reflect the current state of evidence and thought in the area of PsA management, ... several of the recommendations are strongly based on expert opinion, which in turn is based on clinical practice that has emerged in certain institutions, rather than available evidence," wrote the authors. "This is due to the paucity of data in the field of PsA."

The first recommendation, agreed upon unanimously by the task force, is that "in the vast majority of PsA patients, NSAIDs [nonsteroidal anti-inflammatory drugs] should be used as first-line treatment, although the data regarding the usefulness of NSAIDs in PsA are limited."

The task force conceded that in the setting of cardiovascular or gastrointestinal disease, these drugs, including cyclooxygenase-2 inhibitors – which data suggest are as effective as nonselective NSAIDs for PsA – may not be appropriate.

A second recommendation concerned the "early" use of disease-modifying antirheumatic drugs (DMARDs), specifically within 1 year of diagnosis for patients with active disease (i.e., one or more inflamed/tender joints) whose symptoms are unrelieved by NSAIDs.

However, "regarding the choice of a DMARD, here again there are few data and almost no head-to-head comparisons," wrote the authors.

Nevertheless, "the experts recommended methotrexate as the first-choice DMARD ... based in particular on broad therapeutic dose ranges, different application forms [oral or subcutaneous preparations], and available data in PsA and in other inflammatory diseases."

"In the vast majority of PsA patients, NSAIDs should be used as first-line treatment."

"Transaminase enzymes should be carefully monitored in patients with PsA who receive treatment with methotrexate or leflunomide," especially in the setting of comorbid alcohol abuse, diabetes, or statin therapy, they added.

The authors also weighed in on the use of steroids, especially in localized disease. "Intra-articular steroids are efficacious for mono/oligoarthritis or single joint flares in otherwise well-controlled polyarthritis," they wrote. Systemic steroid use, however, should be undertaken with caution, in light of case reports of skin flares that occur at the time of tapering. And when doses are being tapered, "attention should be paid to the potential worsening of skin disease (rebound)," they added.

Finally, the group addressed the use of tumor necrosis factor inhibitors, which can be considered in the event of "treatment failure," defined as an inability to reach target low disease activity after 3-6 months of treatment. In a very few patients, TNF inhibitors may be considered as a first-line treatment in DMARD-naive patients with very active disease. This recommendation is based entirely on expert opinion; there are no data to support it.

"TNF inhibitors (adalimumab, etanercept, golimumab, and infliximab) have demonstrated efficacy in PsA, both for skin and joint involvement, as well as in preventing radiographic damage," wrote the authors.

They added: "This information may be taken into consideration for the choice of TNF inhibitors in patients with clinically significant skin involvement."

The development of the recommendations was sponsored by EULAR. Several of the authors of this article disclosed financial relationships to numerous pharmaceutical companies and the makers of drugs used in PsA treatment.

Use of disease-modifying antirheumatic drugs like methotrexate, sulfasalazine, and leflunomide may improve the outcome of severe psoriatic arthritis if they are given earlier in the course of the disease.

That is one of the recommendations from a new set of guidelines on the treatment of psoriatic arthritis (PsA), issued by a European League Against Rheumatism (EULAR) task force and published online Sept. 27 in Annals of the Rheumatic Diseases.

According to Dr. Laure Gossec, lead author of the report, the recommendations from 28 rheumatologists, 2 patients, an infectious disease specialist, a dermatologist, a physiotherapist, and 2 rheumatology fellows are meant to offer some guidance for what is often a "clinically heterogeneous" disease with few available high-quality studies.

"The treatment of psoriatic arthritis has changed dramatically over recent years, despite the lack of sufficient knowledge on etiology and detailed pathogenesis," wrote Dr. Gossec of Paris Descartes University and colleagues (Ann. Rheum. Dis. 2011 [doi:10.1136/annrheumdis-2011-200350]).

And although the new guidelines "reflect the current state of evidence and thought in the area of PsA management, ... several of the recommendations are strongly based on expert opinion, which in turn is based on clinical practice that has emerged in certain institutions, rather than available evidence," wrote the authors. "This is due to the paucity of data in the field of PsA."

The first recommendation, agreed upon unanimously by the task force, is that "in the vast majority of PsA patients, NSAIDs [nonsteroidal anti-inflammatory drugs] should be used as first-line treatment, although the data regarding the usefulness of NSAIDs in PsA are limited."

The task force conceded that in the setting of cardiovascular or gastrointestinal disease, these drugs, including cyclooxygenase-2 inhibitors – which data suggest are as effective as nonselective NSAIDs for PsA – may not be appropriate.

A second recommendation concerned the "early" use of disease-modifying antirheumatic drugs (DMARDs), specifically within 1 year of diagnosis for patients with active disease (i.e., one or more inflamed/tender joints) whose symptoms are unrelieved by NSAIDs.

However, "regarding the choice of a DMARD, here again there are few data and almost no head-to-head comparisons," wrote the authors.

Nevertheless, "the experts recommended methotrexate as the first-choice DMARD ... based in particular on broad therapeutic dose ranges, different application forms [oral or subcutaneous preparations], and available data in PsA and in other inflammatory diseases."

"In the vast majority of PsA patients, NSAIDs should be used as first-line treatment."

"Transaminase enzymes should be carefully monitored in patients with PsA who receive treatment with methotrexate or leflunomide," especially in the setting of comorbid alcohol abuse, diabetes, or statin therapy, they added.

The authors also weighed in on the use of steroids, especially in localized disease. "Intra-articular steroids are efficacious for mono/oligoarthritis or single joint flares in otherwise well-controlled polyarthritis," they wrote. Systemic steroid use, however, should be undertaken with caution, in light of case reports of skin flares that occur at the time of tapering. And when doses are being tapered, "attention should be paid to the potential worsening of skin disease (rebound)," they added.

Finally, the group addressed the use of tumor necrosis factor inhibitors, which can be considered in the event of "treatment failure," defined as an inability to reach target low disease activity after 3-6 months of treatment. In a very few patients, TNF inhibitors may be considered as a first-line treatment in DMARD-naive patients with very active disease. This recommendation is based entirely on expert opinion; there are no data to support it.

"TNF inhibitors (adalimumab, etanercept, golimumab, and infliximab) have demonstrated efficacy in PsA, both for skin and joint involvement, as well as in preventing radiographic damage," wrote the authors.

They added: "This information may be taken into consideration for the choice of TNF inhibitors in patients with clinically significant skin involvement."

The development of the recommendations was sponsored by EULAR. Several of the authors of this article disclosed financial relationships to numerous pharmaceutical companies and the makers of drugs used in PsA treatment.

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, wrote Dr. Melena D. Bellin and colleagues.

“This procedure should be considered in children with [chronic pancreatitis] when medical and endoscopic modalities have failed” and may be a better alternative to the current surgical standard of care – partial resection and drainage, the authors said.

Dr. Bellin of the endocrinology division in the department of pediatrics at the University of Minnesota, Minneapolis, and her associates studied 19 consecutive children aged 5–18 years who underwent total pancreatectomy with islet autotransplant into the portal vein during 2006–2009 at her institution (Clin. Gastroenterol. Hepatol. 2011 September [doi:10.1016/j.cgh.2011.04.024].

According to the authors, only three centers around the world have completed more than 50 of these procedures, with the bulk of the experience occurring in the adult population.

All patients had a diagnosis of chronic pancreatitis (CP), and had previously failed medical treatment, endoscopic treatment or both.

With their parents' help, patients completed the Medical Outcomes Study 36-item short form (SF-36) questionnaire at 1 week before and at 3, 6, and 12 months after surgery, and then annually. The scores range between 0 and 100 and are divided into eight subscales which in turn make up a Physical Component Summary (PCS) and a Mental Component Summary (MCS) score, with higher numbers signifying better health.

At baseline, all 13 patients required daily or intermittent narcotics. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. “Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34,” Dr. Bellin and her associates wrote. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50. Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance. Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely, “2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose.”

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin dependent and have variable HbA_1c levels, perhaps necessitating a “shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures,” they recommended.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, wrote Dr. Melena D. Bellin and colleagues.

“This procedure should be considered in children with [chronic pancreatitis] when medical and endoscopic modalities have failed” and may be a better alternative to the current surgical standard of care – partial resection and drainage, the authors said.

Dr. Bellin of the endocrinology division in the department of pediatrics at the University of Minnesota, Minneapolis, and her associates studied 19 consecutive children aged 5–18 years who underwent total pancreatectomy with islet autotransplant into the portal vein during 2006–2009 at her institution (Clin. Gastroenterol. Hepatol. 2011 September [doi:10.1016/j.cgh.2011.04.024].

According to the authors, only three centers around the world have completed more than 50 of these procedures, with the bulk of the experience occurring in the adult population.

All patients had a diagnosis of chronic pancreatitis (CP), and had previously failed medical treatment, endoscopic treatment or both.

With their parents' help, patients completed the Medical Outcomes Study 36-item short form (SF-36) questionnaire at 1 week before and at 3, 6, and 12 months after surgery, and then annually. The scores range between 0 and 100 and are divided into eight subscales which in turn make up a Physical Component Summary (PCS) and a Mental Component Summary (MCS) score, with higher numbers signifying better health.

At baseline, all 13 patients required daily or intermittent narcotics. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. “Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34,” Dr. Bellin and her associates wrote. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50. Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance. Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely, “2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose.”

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin dependent and have variable HbA_1c levels, perhaps necessitating a “shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures,” they recommended.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, wrote Dr. Melena D. Bellin and colleagues.

“This procedure should be considered in children with [chronic pancreatitis] when medical and endoscopic modalities have failed” and may be a better alternative to the current surgical standard of care – partial resection and drainage, the authors said.

Dr. Bellin of the endocrinology division in the department of pediatrics at the University of Minnesota, Minneapolis, and her associates studied 19 consecutive children aged 5–18 years who underwent total pancreatectomy with islet autotransplant into the portal vein during 2006–2009 at her institution (Clin. Gastroenterol. Hepatol. 2011 September [doi:10.1016/j.cgh.2011.04.024].

According to the authors, only three centers around the world have completed more than 50 of these procedures, with the bulk of the experience occurring in the adult population.

All patients had a diagnosis of chronic pancreatitis (CP), and had previously failed medical treatment, endoscopic treatment or both.

With their parents' help, patients completed the Medical Outcomes Study 36-item short form (SF-36) questionnaire at 1 week before and at 3, 6, and 12 months after surgery, and then annually. The scores range between 0 and 100 and are divided into eight subscales which in turn make up a Physical Component Summary (PCS) and a Mental Component Summary (MCS) score, with higher numbers signifying better health.

At baseline, all 13 patients required daily or intermittent narcotics. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. “Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34,” Dr. Bellin and her associates wrote. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50. Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance. Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely, “2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose.”

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin dependent and have variable HbA_1c levels, perhaps necessitating a “shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures,” they recommended.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.