Denise Napoli

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Digital rectal examination had a highly positive predictive value for diagnosing dyssynergia in patients with chronic functional constipation, wrote Dr. Satish S.C. Rao and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

In what they called the first study to examine the use of digital rectal exam (DRE) in identifying dyssynergia, the authors looked at 209 patients (191 men) referred to a specialized defecation disorders clinic who fulfilled Rome III criteria for functional constipation (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.06.031]).

The Rome III criteria, developed in 2006, define functional constipation as involving at least two of the following symptoms occurring with 25% of defecations: straining, lumpy or hard stools, feeling of incomplete defecation, feeling of blockage, or use of manual maneuvers. Having fewer than three defecations per week is also a symptom.

The criteria also stipulate that for functional constipation to be present, loose stools must be rare without laxative use, and irritable bowel syndrome must be ruled out.

Patients who met these criteria underwent both a DRE and anorectal manometry, with the latter considered the gold standard for the diagnosis of dyssynergia. The same experienced examiner performed all of the digital exams in the study.

Overall, 183 of the patients received a diagnosis of dyssynergia based on manometry. Of these, 134 (73%) also had "features of dyssynergia" according to digital exam. Four patients who had no dyssynergia on manometry were misidentified as dyssynergic on digital exam.

That translated to an overall sensitivity of DRE for dyssynergia diagnosis of 75% and a specificity of 87%, with a positive predictive value of 97%.

Dr. Rao, of the University of Iowa, Iowa City, and his colleagues, also found "good" agreement for normal resting anal sphincter tone between DRE and manometry (87 and 101, respectively, or 86%) and "fair" agreement for increased resting sphincter tone (12 and 28, or 43%). There was low agreement between the two modalities for decreased resting sphincter tone (12 and 80, or 15%).

Despite the value of DRE shown in this study – including its low cost and ease of use – the authors commented that previous studies have shown that medical students are not being trained to use the technique.

"It is imperative that serious efforts are made by faculty mentors during medical school and residency training to improve and facilitate the acquisition of this clinical skill," wrote the authors. "This is particularly relevant as sophisticated tests such as anorectal manometry and balloon expulsion test, although useful and diagnostic, are not widely available."

The authors pointed out several limitations, including the fact that anorectal manometry "may be falsely positive for dyssynergia in 15% of asymptomatic subjects," according to one study cited by the authors.

In addition, "even when performed meticulously, several subjects had low resting and low squeeze sphincter pressure on [anorectal manometry], but were felt to have normal resting sphincter tone and normal squeeze tone during digital rectal examination," they wrote. "This may be due to an apprehension or fear of DRE on the part of a subject that may have temporarily and falsely increased resting tone."

The authors reported having no conflicts of interest related to this study. Dr. Rao disclosed support from the National Institutes of Health. Another researcher was supported by Chulalongkorn University, Bangkok.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were found on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, wrote Dr. Mitchal A. Schreiner and his colleagues in the November issue of Gastroenterology.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be "especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia."

In what they called the "first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy," the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All patients were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a "sawtooth appearance in the colonic crypts." Proximal lesions were defined as those located proximal to the descending colon. The researchers also assessed "large" ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, "which would have implications for surveillance," wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later. "The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR 3.14; 95% CI 1.59-6.20), but not advanced neoplasia (OR 2.09; 95% CI 0.44-9.87)," they wrote.

However, "the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses."

The authors pointed out several limitations of the study. For one, "the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability," although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, "since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic."

Dr. Schreiner and his colleagues wrote that they had no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Major Finding: Among patients with MD, the median age at death was significantly higher for white males than it was for black males (33 years vs. 23 years).

Data Source: The 1986-2005 National Center for Health Statistics' Multiple Cause Mortality Files.

Disclosures: Lead investigator Dr. Kenneson reported research grants from the CDC; a coinvestigator reported receiving advisory fees and research support from several pharmaceutical companies and MD-related support from foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study's 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., and her colleagues.

With her associates, Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, looked at records from the National Center for Health Statistics' Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.”

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors noted that “while the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

Major Finding: Among patients with MD, the median age at death was significantly higher for white males than it was for black males (33 years vs. 23 years).

Data Source: The 1986-2005 National Center for Health Statistics' Multiple Cause Mortality Files.

Disclosures: Lead investigator Dr. Kenneson reported research grants from the CDC; a coinvestigator reported receiving advisory fees and research support from several pharmaceutical companies and MD-related support from foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study's 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., and her colleagues.

With her associates, Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, looked at records from the National Center for Health Statistics' Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.”

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors noted that “while the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

Major Finding: Among patients with MD, the median age at death was significantly higher for white males than it was for black males (33 years vs. 23 years).

Data Source: The 1986-2005 National Center for Health Statistics' Multiple Cause Mortality Files.

Disclosures: Lead investigator Dr. Kenneson reported research grants from the CDC; a coinvestigator reported receiving advisory fees and research support from several pharmaceutical companies and MD-related support from foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study's 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., and her colleagues.

With her associates, Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, looked at records from the National Center for Health Statistics' Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.”

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors noted that “while the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

Acts Against Painful Diseases

Before House of Representatives members went home to campaign this fall, they passed two bills that would advance national efforts against degenerative joint diseases. Led by Rep. Anna Eshoo (D-Calif.), the House passed the Arthritis Prevention, Control, and Cure Act (H.R. 1210), which would expand public health initiatives that address arthritis and focus federal research and training support on pediatric rheumatology. On the same day, the Scleroderma Research and Awareness Act (H.R. 2408), introduced by Rep. Lois Capps (D-Calif.) and Rep. Vern Ehlers (R-Mich.), also passed the House. The bill would direct the National Institutes of Health to conduct research on scleroderma and related conditions including pulmonary hypertension, gastroparesis, Raynaud's phenomenon, and Sjögren's syndrome. The relevant advocacy organizations praised the sponsors and applauded the bills' goals. In its statement, the Arthritis Foundation called on the Senate to pass its version of the arthritis act (S. 984) before the end of the year. Scleroderma Foundation board chair Joseph P. Camerino, Ph.D., said, “With the passage of this landmark legislation, the scleroderma community has even greater hope that a cure will be found.”

Grants Fund Lupus Research

The Lupus Foundation of America has made six new grants for studies into what it considers neglected areas of lupus research: pediatric lupus, reproductive health issues in lupus, lupus nephritis, and neuropsychiatric lupus. “The research funded this year tackles some of the most complex and challenging areas of lupus research,” said Sandra C. Raymond, president and CEO of the Washington, D.C.–based foundation. “These areas of research have suffered from a lack of resources, and in some cases have seen little advancement.” With the new grants, Dr. Bruce C. Richardson of the University of Michigan in Ann Arbor will study the genetics of male lupus; Dr. Richard K. Burt of Northwestern University in Chicago will look at hematopoietic stem cell transplantation in lupus; Dr. Richard J. Quigg of the University of Chicago will study complement manipulation in lupus nephritis; Dr. Martin G. Pomper of Johns Hopkins University in Baltimore will assess imaging microglial activation in neuropsychiatric lupus; Dr. Michelle A. Petri of Johns Hopkins will study the use of levothyroxine in pregnant systemic lupus erythematosus (SLE) patients; and Dr. Kathleen M. O'Neil of the University of Oklahoma in Oklahoma City will look at the effect of puberty on SLE.

World Arthritis Day Celebrated

If you were feeling blue on Oct. 12, maybe it was the glow of the official color of World Arthritis Day. The event, spearheaded by the European League Against Rheumatism (EULAR) and the Arthritis Foundation, included bathing landmarks such as Niagara Falls in blue light. The purpose of World Arthritis Day is to “raise awareness of arthritis in all its forms among the medical community, people with arthritis, and the general public; to influence public policy by making decision makers aware of the burden of arthritis and the steps which can be taken to ease it; to ensure all people with arthritis and their caregivers are aware of the vast support network available to them,” according to the EULAR Web site on the commemoration (

www.worldarthritisday.org

Nursing Expansion Called For

Nurses' roles and responsibilities should change significantly to meet the increased demand for care created by health care reform, according to an Institute of Medicine report that immediately drew criticism from the American Medical Association. The report urged the removal of regulatory and institutional obstacles to nurses who take on additional patient-care duties. To handle these new responsibilities, nurses should receive higher levels of training through an improved education system, including a new residency program and additional opportunities for lifelong learning, the IOM report said. The AMA took issue with the report's call to expand nurses' scope of practice, saying that nurse practitioners don't have nearly the amount of training and clinical experience that doctors do. “With a shortage of both nurses and physicians, increasing the responsibility of nurses is not the answer to the physician shortage,” said AMA board member Rebecca J. Patchin in a statement.

First EHR-Certifying Bodies Named

A nonprofit organization that is dedicated to health information technology and a software-testing lab have been chosen as the first two bodies to officially test and certify electronic health record systems for the federal government. The Certification Commission for Health Information Technology and the Drummond Group can immediately begin certifying EHR systems as being HHS compliant, the Department of Health and Human Services said in an announcement. Now that HHS has named the certifying organizations, vendors can start applying for certification of the EHR systems and physicians soon should be able to purchase certified products, the HHS said.

Acts Against Painful Diseases

Before House of Representatives members went home to campaign this fall, they passed two bills that would advance national efforts against degenerative joint diseases. Led by Rep. Anna Eshoo (D-Calif.), the House passed the Arthritis Prevention, Control, and Cure Act (H.R. 1210), which would expand public health initiatives that address arthritis and focus federal research and training support on pediatric rheumatology. On the same day, the Scleroderma Research and Awareness Act (H.R. 2408), introduced by Rep. Lois Capps (D-Calif.) and Rep. Vern Ehlers (R-Mich.), also passed the House. The bill would direct the National Institutes of Health to conduct research on scleroderma and related conditions including pulmonary hypertension, gastroparesis, Raynaud's phenomenon, and Sjögren's syndrome. The relevant advocacy organizations praised the sponsors and applauded the bills' goals. In its statement, the Arthritis Foundation called on the Senate to pass its version of the arthritis act (S. 984) before the end of the year. Scleroderma Foundation board chair Joseph P. Camerino, Ph.D., said, “With the passage of this landmark legislation, the scleroderma community has even greater hope that a cure will be found.”

Grants Fund Lupus Research

The Lupus Foundation of America has made six new grants for studies into what it considers neglected areas of lupus research: pediatric lupus, reproductive health issues in lupus, lupus nephritis, and neuropsychiatric lupus. “The research funded this year tackles some of the most complex and challenging areas of lupus research,” said Sandra C. Raymond, president and CEO of the Washington, D.C.–based foundation. “These areas of research have suffered from a lack of resources, and in some cases have seen little advancement.” With the new grants, Dr. Bruce C. Richardson of the University of Michigan in Ann Arbor will study the genetics of male lupus; Dr. Richard K. Burt of Northwestern University in Chicago will look at hematopoietic stem cell transplantation in lupus; Dr. Richard J. Quigg of the University of Chicago will study complement manipulation in lupus nephritis; Dr. Martin G. Pomper of Johns Hopkins University in Baltimore will assess imaging microglial activation in neuropsychiatric lupus; Dr. Michelle A. Petri of Johns Hopkins will study the use of levothyroxine in pregnant systemic lupus erythematosus (SLE) patients; and Dr. Kathleen M. O'Neil of the University of Oklahoma in Oklahoma City will look at the effect of puberty on SLE.

World Arthritis Day Celebrated

If you were feeling blue on Oct. 12, maybe it was the glow of the official color of World Arthritis Day. The event, spearheaded by the European League Against Rheumatism (EULAR) and the Arthritis Foundation, included bathing landmarks such as Niagara Falls in blue light. The purpose of World Arthritis Day is to “raise awareness of arthritis in all its forms among the medical community, people with arthritis, and the general public; to influence public policy by making decision makers aware of the burden of arthritis and the steps which can be taken to ease it; to ensure all people with arthritis and their caregivers are aware of the vast support network available to them,” according to the EULAR Web site on the commemoration (

www.worldarthritisday.org

Nursing Expansion Called For

Nurses' roles and responsibilities should change significantly to meet the increased demand for care created by health care reform, according to an Institute of Medicine report that immediately drew criticism from the American Medical Association. The report urged the removal of regulatory and institutional obstacles to nurses who take on additional patient-care duties. To handle these new responsibilities, nurses should receive higher levels of training through an improved education system, including a new residency program and additional opportunities for lifelong learning, the IOM report said. The AMA took issue with the report's call to expand nurses' scope of practice, saying that nurse practitioners don't have nearly the amount of training and clinical experience that doctors do. “With a shortage of both nurses and physicians, increasing the responsibility of nurses is not the answer to the physician shortage,” said AMA board member Rebecca J. Patchin in a statement.

First EHR-Certifying Bodies Named

A nonprofit organization that is dedicated to health information technology and a software-testing lab have been chosen as the first two bodies to officially test and certify electronic health record systems for the federal government. The Certification Commission for Health Information Technology and the Drummond Group can immediately begin certifying EHR systems as being HHS compliant, the Department of Health and Human Services said in an announcement. Now that HHS has named the certifying organizations, vendors can start applying for certification of the EHR systems and physicians soon should be able to purchase certified products, the HHS said.

Acts Against Painful Diseases

Before House of Representatives members went home to campaign this fall, they passed two bills that would advance national efforts against degenerative joint diseases. Led by Rep. Anna Eshoo (D-Calif.), the House passed the Arthritis Prevention, Control, and Cure Act (H.R. 1210), which would expand public health initiatives that address arthritis and focus federal research and training support on pediatric rheumatology. On the same day, the Scleroderma Research and Awareness Act (H.R. 2408), introduced by Rep. Lois Capps (D-Calif.) and Rep. Vern Ehlers (R-Mich.), also passed the House. The bill would direct the National Institutes of Health to conduct research on scleroderma and related conditions including pulmonary hypertension, gastroparesis, Raynaud's phenomenon, and Sjögren's syndrome. The relevant advocacy organizations praised the sponsors and applauded the bills' goals. In its statement, the Arthritis Foundation called on the Senate to pass its version of the arthritis act (S. 984) before the end of the year. Scleroderma Foundation board chair Joseph P. Camerino, Ph.D., said, “With the passage of this landmark legislation, the scleroderma community has even greater hope that a cure will be found.”

Grants Fund Lupus Research

The Lupus Foundation of America has made six new grants for studies into what it considers neglected areas of lupus research: pediatric lupus, reproductive health issues in lupus, lupus nephritis, and neuropsychiatric lupus. “The research funded this year tackles some of the most complex and challenging areas of lupus research,” said Sandra C. Raymond, president and CEO of the Washington, D.C.–based foundation. “These areas of research have suffered from a lack of resources, and in some cases have seen little advancement.” With the new grants, Dr. Bruce C. Richardson of the University of Michigan in Ann Arbor will study the genetics of male lupus; Dr. Richard K. Burt of Northwestern University in Chicago will look at hematopoietic stem cell transplantation in lupus; Dr. Richard J. Quigg of the University of Chicago will study complement manipulation in lupus nephritis; Dr. Martin G. Pomper of Johns Hopkins University in Baltimore will assess imaging microglial activation in neuropsychiatric lupus; Dr. Michelle A. Petri of Johns Hopkins will study the use of levothyroxine in pregnant systemic lupus erythematosus (SLE) patients; and Dr. Kathleen M. O'Neil of the University of Oklahoma in Oklahoma City will look at the effect of puberty on SLE.

World Arthritis Day Celebrated

If you were feeling blue on Oct. 12, maybe it was the glow of the official color of World Arthritis Day. The event, spearheaded by the European League Against Rheumatism (EULAR) and the Arthritis Foundation, included bathing landmarks such as Niagara Falls in blue light. The purpose of World Arthritis Day is to “raise awareness of arthritis in all its forms among the medical community, people with arthritis, and the general public; to influence public policy by making decision makers aware of the burden of arthritis and the steps which can be taken to ease it; to ensure all people with arthritis and their caregivers are aware of the vast support network available to them,” according to the EULAR Web site on the commemoration (

www.worldarthritisday.org

Nursing Expansion Called For

Nurses' roles and responsibilities should change significantly to meet the increased demand for care created by health care reform, according to an Institute of Medicine report that immediately drew criticism from the American Medical Association. The report urged the removal of regulatory and institutional obstacles to nurses who take on additional patient-care duties. To handle these new responsibilities, nurses should receive higher levels of training through an improved education system, including a new residency program and additional opportunities for lifelong learning, the IOM report said. The AMA took issue with the report's call to expand nurses' scope of practice, saying that nurse practitioners don't have nearly the amount of training and clinical experience that doctors do. “With a shortage of both nurses and physicians, increasing the responsibility of nurses is not the answer to the physician shortage,” said AMA board member Rebecca J. Patchin in a statement.

First EHR-Certifying Bodies Named

A nonprofit organization that is dedicated to health information technology and a software-testing lab have been chosen as the first two bodies to officially test and certify electronic health record systems for the federal government. The Certification Commission for Health Information Technology and the Drummond Group can immediately begin certifying EHR systems as being HHS compliant, the Department of Health and Human Services said in an announcement. Now that HHS has named the certifying organizations, vendors can start applying for certification of the EHR systems and physicians soon should be able to purchase certified products, the HHS said.

The presence of large, serrated polyps was associated with a greater risk of colorectal cancer than any other factor, including age, sex, size of adenomas, and number of adenomas, reported Dr. Sakiko Hiraoka and colleagues.

Moreover, the cancers in patients with large serrated polyps were more than twice as likely to be proximal as opposed to distal, the authors reported (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.07.011]).

Dr. Hiraoka of the department of gastroenterology and hepatology at Okayama (Japan) University, and colleagues performed a database study including 10,199 patients who had their first colonoscopy at Dr. Hiraoka's institution or at 1 of 14 affiliated hospitals between June 2005 and May 2008.

Patients had to have no prior history of resection, no prior diagnosis of inflammatory bowel disease, and no familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer.

The mean age was 58.9 years, with 51.5% being male. Overall, 8.6% of the 10,199 patients were having a standard screening colonoscopy, while 41.5% underwent colonoscopy secondary to a positive fecal occult blood test. Another 20.6% had the colonoscopy because of abdominal symptoms, 13.2% due to rectal bleeding, and 2.4% because of anemia or another reason.

In the cohort, there were a total of 1,573 patients (15.4%) with advanced neoplasia, including 708 (6.9%) with colorectal cancer and 140 (1.4%) with large serrated polyps (10 mm or greater).

Dr. Hiraoka and colleagues found that out of several known risk factors for colorectal cancer, the presence of large serrated polyps carried the greatest risk, with an odds ratio of 3.34 (P less than .0001).

The next-highest risk among the variables studied was age of 65 years or older (OR, 2.63; P less than .0001).

Having four or more adenomas on colonoscopy carried an OR of 1.65 (P less than .01), and having an adenoma greater than 10 mm carried an OR of 1.56 (P less than .001). Male gender did not carry any significant increased risk in this analysis.

The authors then looked at the predictors of advanced neoplasia and cancer according to location.

Dr. Hiraoka and colleagues found that large serrated polyps were more than twice as likely to develop into proximal colon cancer than into distal colorectal cancer (OR for proximal cancer, 4.79; P less than .0001; OR for distal colorectal cancer, 2.23; P less than .01).

The correlation between serrated polyps and proximal cancer may be a manifestation of common molecular backgrounds between them, including BRAF mutation, according to the authors.

However, it does not follow that large serrated polyps necessarily progress into colorectal cancers themselves. “In fact, CRCs which develop in [hyperplastic polyposis syndrome] patients are largely microsatellite stable rather than [microsatellite instability-high] MSI-H, suggesting that serrated polyps do not always progress into MSI-H cancer,” they commented.

The authors noted that one advantage of their study was the “relatively large” proportion of patients with colorectal neoplasia.

However, they noted that their study did not involve correlating neoplasia with the specific type of serrated polyp, which was a limitation.

The presence of large, serrated polyps was associated with a greater risk of colorectal cancer than any other factor, including age, sex, size of adenomas, and number of adenomas, reported Dr. Sakiko Hiraoka and colleagues.

Moreover, the cancers in patients with large serrated polyps were more than twice as likely to be proximal as opposed to distal, the authors reported (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.07.011]).

Dr. Hiraoka of the department of gastroenterology and hepatology at Okayama (Japan) University, and colleagues performed a database study including 10,199 patients who had their first colonoscopy at Dr. Hiraoka's institution or at 1 of 14 affiliated hospitals between June 2005 and May 2008.

Patients had to have no prior history of resection, no prior diagnosis of inflammatory bowel disease, and no familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer.

The mean age was 58.9 years, with 51.5% being male. Overall, 8.6% of the 10,199 patients were having a standard screening colonoscopy, while 41.5% underwent colonoscopy secondary to a positive fecal occult blood test. Another 20.6% had the colonoscopy because of abdominal symptoms, 13.2% due to rectal bleeding, and 2.4% because of anemia or another reason.

In the cohort, there were a total of 1,573 patients (15.4%) with advanced neoplasia, including 708 (6.9%) with colorectal cancer and 140 (1.4%) with large serrated polyps (10 mm or greater).

Dr. Hiraoka and colleagues found that out of several known risk factors for colorectal cancer, the presence of large serrated polyps carried the greatest risk, with an odds ratio of 3.34 (P less than .0001).

The next-highest risk among the variables studied was age of 65 years or older (OR, 2.63; P less than .0001).

Having four or more adenomas on colonoscopy carried an OR of 1.65 (P less than .01), and having an adenoma greater than 10 mm carried an OR of 1.56 (P less than .001). Male gender did not carry any significant increased risk in this analysis.

The authors then looked at the predictors of advanced neoplasia and cancer according to location.

Dr. Hiraoka and colleagues found that large serrated polyps were more than twice as likely to develop into proximal colon cancer than into distal colorectal cancer (OR for proximal cancer, 4.79; P less than .0001; OR for distal colorectal cancer, 2.23; P less than .01).

The correlation between serrated polyps and proximal cancer may be a manifestation of common molecular backgrounds between them, including BRAF mutation, according to the authors.

However, it does not follow that large serrated polyps necessarily progress into colorectal cancers themselves. “In fact, CRCs which develop in [hyperplastic polyposis syndrome] patients are largely microsatellite stable rather than [microsatellite instability-high] MSI-H, suggesting that serrated polyps do not always progress into MSI-H cancer,” they commented.

The authors noted that one advantage of their study was the “relatively large” proportion of patients with colorectal neoplasia.

However, they noted that their study did not involve correlating neoplasia with the specific type of serrated polyp, which was a limitation.

The presence of large, serrated polyps was associated with a greater risk of colorectal cancer than any other factor, including age, sex, size of adenomas, and number of adenomas, reported Dr. Sakiko Hiraoka and colleagues.

Moreover, the cancers in patients with large serrated polyps were more than twice as likely to be proximal as opposed to distal, the authors reported (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.07.011]).

Dr. Hiraoka of the department of gastroenterology and hepatology at Okayama (Japan) University, and colleagues performed a database study including 10,199 patients who had their first colonoscopy at Dr. Hiraoka's institution or at 1 of 14 affiliated hospitals between June 2005 and May 2008.

Patients had to have no prior history of resection, no prior diagnosis of inflammatory bowel disease, and no familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer.

The mean age was 58.9 years, with 51.5% being male. Overall, 8.6% of the 10,199 patients were having a standard screening colonoscopy, while 41.5% underwent colonoscopy secondary to a positive fecal occult blood test. Another 20.6% had the colonoscopy because of abdominal symptoms, 13.2% due to rectal bleeding, and 2.4% because of anemia or another reason.

In the cohort, there were a total of 1,573 patients (15.4%) with advanced neoplasia, including 708 (6.9%) with colorectal cancer and 140 (1.4%) with large serrated polyps (10 mm or greater).

Dr. Hiraoka and colleagues found that out of several known risk factors for colorectal cancer, the presence of large serrated polyps carried the greatest risk, with an odds ratio of 3.34 (P less than .0001).

The next-highest risk among the variables studied was age of 65 years or older (OR, 2.63; P less than .0001).

Having four or more adenomas on colonoscopy carried an OR of 1.65 (P less than .01), and having an adenoma greater than 10 mm carried an OR of 1.56 (P less than .001). Male gender did not carry any significant increased risk in this analysis.

The authors then looked at the predictors of advanced neoplasia and cancer according to location.

Dr. Hiraoka and colleagues found that large serrated polyps were more than twice as likely to develop into proximal colon cancer than into distal colorectal cancer (OR for proximal cancer, 4.79; P less than .0001; OR for distal colorectal cancer, 2.23; P less than .01).

The correlation between serrated polyps and proximal cancer may be a manifestation of common molecular backgrounds between them, including BRAF mutation, according to the authors.

However, it does not follow that large serrated polyps necessarily progress into colorectal cancers themselves. “In fact, CRCs which develop in [hyperplastic polyposis syndrome] patients are largely microsatellite stable rather than [microsatellite instability-high] MSI-H, suggesting that serrated polyps do not always progress into MSI-H cancer,” they commented.

The authors noted that one advantage of their study was the “relatively large” proportion of patients with colorectal neoplasia.

However, they noted that their study did not involve correlating neoplasia with the specific type of serrated polyp, which was a limitation.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug's maker, Rigel Pharmaceuticals.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

All patients met the American College of Rheumatology's 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/wk), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, 31% of the twice-daily R788 group achieved remission (defined by a Disease Activity Score–28 less than 2.6) by 6 months, compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

Three authors, including Dr. Weinblatt, disclosed financial relationships to multiple pharmaceutical makers, including Rigel; the remaining three are employees of Rigel.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug's maker, Rigel Pharmaceuticals.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

All patients met the American College of Rheumatology's 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/wk), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, 31% of the twice-daily R788 group achieved remission (defined by a Disease Activity Score–28 less than 2.6) by 6 months, compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

Three authors, including Dr. Weinblatt, disclosed financial relationships to multiple pharmaceutical makers, including Rigel; the remaining three are employees of Rigel.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug's maker, Rigel Pharmaceuticals.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

All patients met the American College of Rheumatology's 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/wk), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, 31% of the twice-daily R788 group achieved remission (defined by a Disease Activity Score–28 less than 2.6) by 6 months, compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

Three authors, including Dr. Weinblatt, disclosed financial relationships to multiple pharmaceutical makers, including Rigel; the remaining three are employees of Rigel.

Major Finding: Having nondysplastic serrated polyps located proximal to the descending colon carried an odds ratio of 1.90 for having synchronous advanced dysplasia, compared with patients without the lesions; having large nondysplastic serrated polyps tripled the risk.

Data Source: A study of 3,121 asymptomatic patients (96% male) aged 50-75 years who received a screening colonoscopy at 1 of 13 VA medical centers.

Disclosures: The authors disclosed no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were discovered on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, reported Dr. Mitchal A. Schreiner and his colleagues.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be “especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia.”

In what they called the “first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy,” the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All of the patients in the study were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a “sawtooth appearance in the colonic crypts.” Proximal lesions were defined as those that were located proximal to the descending colon. The researchers also assessed “large” ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, “which would have implications for surveillance,” wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR, 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later.

“The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR, 3.14; 95% CI, 1.59-6.20), but not advanced neoplasia (OR, 2.09; 95% CI, 0.44-9.87),” they wrote.

However, “the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses,” they noted.

The authors pointed out several limitations of the study. For one, “the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability,” although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, “since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic,” Dr. Schreiner and his associates said.

Major Finding: Having nondysplastic serrated polyps located proximal to the descending colon carried an odds ratio of 1.90 for having synchronous advanced dysplasia, compared with patients without the lesions; having large nondysplastic serrated polyps tripled the risk.

Data Source: A study of 3,121 asymptomatic patients (96% male) aged 50-75 years who received a screening colonoscopy at 1 of 13 VA medical centers.

Disclosures: The authors disclosed no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were discovered on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, reported Dr. Mitchal A. Schreiner and his colleagues.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be “especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia.”

In what they called the “first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy,” the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All of the patients in the study were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a “sawtooth appearance in the colonic crypts.” Proximal lesions were defined as those that were located proximal to the descending colon. The researchers also assessed “large” ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, “which would have implications for surveillance,” wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR, 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later.

“The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR, 3.14; 95% CI, 1.59-6.20), but not advanced neoplasia (OR, 2.09; 95% CI, 0.44-9.87),” they wrote.

However, “the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses,” they noted.

The authors pointed out several limitations of the study. For one, “the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability,” although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, “since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic,” Dr. Schreiner and his associates said.

Major Finding: Having nondysplastic serrated polyps located proximal to the descending colon carried an odds ratio of 1.90 for having synchronous advanced dysplasia, compared with patients without the lesions; having large nondysplastic serrated polyps tripled the risk.

Data Source: A study of 3,121 asymptomatic patients (96% male) aged 50-75 years who received a screening colonoscopy at 1 of 13 VA medical centers.

Disclosures: The authors disclosed no conflicts of interest related to this study, which was supported by the Department of Veterans Affairs.

Patients with proximal, nondysplastic serrated polyps that were discovered on baseline screening colonoscopy were nearly twice as likely to have synchronous advanced neoplasia as were patients without those lesions, reported Dr. Mitchal A. Schreiner and his colleagues.

The risk of finding an adenoma during surveillance also increases in such patients, added Dr. Schreiner of the Portland (Ore.) VA Medical Center (Gastroenterology 2010 November [doi:10.1053/j.gastro.2010.06.074]).

The finding means that when nondysplastic serrated polyps (ND-SPs) are noted, endoscopists must be “especially vigilant and perform high-quality baseline screening exams to ensure detection of patients with advanced neoplasia.”

In what they called the “first large study to examine the outcomes of surveillance colonoscopy in patients with proximal ND-SPs at baseline screening colonoscopy,” the researchers looked at 3,121 asymptomatic patients (96% male) who underwent a screening colonoscopy at 1 of 13 Veterans Affairs medical centers between February 1994 and January 1997. All of the patients in the study were between 50 and 75 years old.

Serrated polyps were defined as any polyp with a “sawtooth appearance in the colonic crypts.” Proximal lesions were defined as those that were located proximal to the descending colon. The researchers also assessed “large” ND-SPs, meaning those greater than 10 mm.

Overall, 801 patients (25.7% of the total cohort) had one or more ND-SPs, including 248 patients with one or more proximal ND-SPs (7.9%). A total of 44 patients (1.4% of the total cohort) had at least one large ND-SP, of which 57% were in the proximal colon.

Among the proximal ND-SP patients, 17.3% were found to have synchronous advanced neoplasia (defined as invasive cancer, adenomas with high-grade dysplasia or villous histology, or tubular adenoma greater than 10 mm). The prevalence among patients with no proximal ND-SPs was 10%. After adjustment for age, that translated into a significant 1.90 odds ratio among the proximal ND-SP patients.

Proximal ND-SP patients also showed an increased likelihood of having three or more synchronous small tubular adenomas (less than 10 mm) on baseline colonoscopy, “which would have implications for surveillance,” wrote the authors. Overall, 10.7% of patients with the proximal ND-SPs had them, compared with 5.3% of patients with no proximal ND-SPs (OR, 2.19).

With regard to large ND-SPs, the 44 patients with these lesions had a particularly striking prevalence of synchronous advanced neoplasia, at 27.3%, compared with 10.3% of those without these lesions, for an age-adjusted OR of 3.37.

Dr. Schreiner and his colleagues also found that having ND-SPs at screening predicted neoplasia on follow-up colonoscopies up to 5.5 years later.

“The presence of a proximal ND-SP on index colonoscopy is associated with an increased risk of any adenoma during surveillance (OR, 3.14; 95% CI, 1.59-6.20), but not advanced neoplasia (OR, 2.09; 95% CI, 0.44-9.87),” they wrote.

However, “the number of subjects in our cohort with a large ND-SP on baseline colonoscopy who had surveillance colonoscopy within 5.5 years (n = 31) was insufficient to perform risk analyses,” they noted.

The authors pointed out several limitations of the study. For one, “the pathologic criteria for the diagnosis of serrated polyps are subject to interobserver variability,” although this study did classify polyps on the basis of input from three separate reviewers.

Additionally, “since the criteria for SSA [sessile serrated adenomas] were developed after our study, we could not perform an analysis which distinguished HP [hyperplastic polyps] and SSA, which are both nondysplastic,” Dr. Schreiner and his associates said.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study.

The Interferon-Free Regimen for the Management of HCV (INFORM-1) study was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 10

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 15 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients were randomized into seven groups to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment and 14 received placebo.

In patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” the authors wrote.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

Median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” they said.

At 14 days – the study's completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

Roche developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune.

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New Treatment Brings Hope, Questions

In an editorial accompanying the article, Dr. David L. Thomas wrote that “we are on the eve of a new era in hepatitis C virus treatment.”

Indeed, he added, for the first 2 decades after the virus was discovered, “only ribavirin and interferon-alfa–related compounds were approved for HCV treatment, and nearly a decade has passed since the last substantive upgrade.”

However, he pointed out some “important limitations” to early-phase trials such as this. For example, although the study met its safety objectives, “the goal of HCV treatment is to eradicate infection,” an end point achieved when HCV RNA cannot be detected in blood at the end of treatment and 6 months later.

Because patients in the study rolled over to pegylated interferon-alfa and ribavirin after completion of study drug treatment, “the study will never tell us about the ultimate efficacy of the combined use of the two direct-acting agents.”

Moreover, “long-term risk of viral resistance with a two-drug direct-acting regimen cannot be confidently assessed, because drug use was directly observed in a clinical trial unit, and only limited resistance testing was presented.”

Even if a treatment with 100% efficacy is ultimately developed, “what is unclear at this stage is whether HCV testing and treatment will penetrate to the prisons, drug-treatment centres, and other venues where many HCV infected individuals are found and unknowingly harbour the virus,” he wrote.

DAVID L. THOMAS, M.D., is professor at Johns Hopkins University in Baltimore. This editorial was published online in the Lancet (2010 Oct. 15 [doi:10.1016/50140-6736(10)61497-3]). He has received drugs for phase IV studies with Merck & Co. and Gilead Sciences Inc., and has received an honorarium from Merck and payment for development of educational materials from companies who in turn receive support from drug companies.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study.

The Interferon-Free Regimen for the Management of HCV (INFORM-1) study was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 10

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 15 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients were randomized into seven groups to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment and 14 received placebo.

In patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” the authors wrote.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

Median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” they said.

At 14 days – the study's completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

Roche developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune.

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New Treatment Brings Hope, Questions

In an editorial accompanying the article, Dr. David L. Thomas wrote that “we are on the eve of a new era in hepatitis C virus treatment.”

Indeed, he added, for the first 2 decades after the virus was discovered, “only ribavirin and interferon-alfa–related compounds were approved for HCV treatment, and nearly a decade has passed since the last substantive upgrade.”

However, he pointed out some “important limitations” to early-phase trials such as this. For example, although the study met its safety objectives, “the goal of HCV treatment is to eradicate infection,” an end point achieved when HCV RNA cannot be detected in blood at the end of treatment and 6 months later.

Because patients in the study rolled over to pegylated interferon-alfa and ribavirin after completion of study drug treatment, “the study will never tell us about the ultimate efficacy of the combined use of the two direct-acting agents.”

Moreover, “long-term risk of viral resistance with a two-drug direct-acting regimen cannot be confidently assessed, because drug use was directly observed in a clinical trial unit, and only limited resistance testing was presented.”

Even if a treatment with 100% efficacy is ultimately developed, “what is unclear at this stage is whether HCV testing and treatment will penetrate to the prisons, drug-treatment centres, and other venues where many HCV infected individuals are found and unknowingly harbour the virus,” he wrote.

DAVID L. THOMAS, M.D., is professor at Johns Hopkins University in Baltimore. This editorial was published online in the Lancet (2010 Oct. 15 [doi:10.1016/50140-6736(10)61497-3]). He has received drugs for phase IV studies with Merck & Co. and Gilead Sciences Inc., and has received an honorarium from Merck and payment for development of educational materials from companies who in turn receive support from drug companies.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study.

The Interferon-Free Regimen for the Management of HCV (INFORM-1) study was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 10

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 15 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients were randomized into seven groups to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment and 14 received placebo.

In patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” the authors wrote.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

Median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” they said.

At 14 days – the study's completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

Roche developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune.

View on the News

New Treatment Brings Hope, Questions

In an editorial accompanying the article, Dr. David L. Thomas wrote that “we are on the eve of a new era in hepatitis C virus treatment.”

Indeed, he added, for the first 2 decades after the virus was discovered, “only ribavirin and interferon-alfa–related compounds were approved for HCV treatment, and nearly a decade has passed since the last substantive upgrade.”

However, he pointed out some “important limitations” to early-phase trials such as this. For example, although the study met its safety objectives, “the goal of HCV treatment is to eradicate infection,” an end point achieved when HCV RNA cannot be detected in blood at the end of treatment and 6 months later.

Because patients in the study rolled over to pegylated interferon-alfa and ribavirin after completion of study drug treatment, “the study will never tell us about the ultimate efficacy of the combined use of the two direct-acting agents.”

Moreover, “long-term risk of viral resistance with a two-drug direct-acting regimen cannot be confidently assessed, because drug use was directly observed in a clinical trial unit, and only limited resistance testing was presented.”

Even if a treatment with 100% efficacy is ultimately developed, “what is unclear at this stage is whether HCV testing and treatment will penetrate to the prisons, drug-treatment centres, and other venues where many HCV infected individuals are found and unknowingly harbour the virus,” he wrote.

DAVID L. THOMAS, M.D., is professor at Johns Hopkins University in Baltimore. This editorial was published online in the Lancet (2010 Oct. 15 [doi:10.1016/50140-6736(10)61497-3]). He has received drugs for phase IV studies with Merck & Co. and Gilead Sciences Inc., and has received an honorarium from Merck and payment for development of educational materials from companies who in turn receive support from drug companies.