Denise Napoli

Combination therapy consisting of ursodiol and either methotrexate or colchicine for primary biliary cirrhosis showed long-term effectiveness, lasting up to 20 years, wrote Dr. John Leung and his colleagues in the September issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2011.05.010).

Dr. Leung, of the department of gastroenterology at Tufts Medical Center, Boston, and his colleagues studied 29 patients with primary biliary cirrhosis, a chronic progressive disease thought to have an autoimmune etiology. The patients were originally part of an 85-patient, double-blind, prospective, randomized controlled trial comparing colchicine and methotrexate from 1988 to 2000, with ursodiol (ursodeoxycholic acid) added to that regimen 3 years after study initiation.

The patients examined in the current study had completed all 10 years of follow-up in the original trial. At completion, "the randomization code was broken and these 29 patients were treated according to their clinical response, personal preference, and tolerance to therapy."

They were then followed for an additional 9-13 years, either at the authors’ institution (21 patients) or via telephone calls and e-mail correspondence with referring physicians.

All patients except one were female, and the median age at the end of the initial 10-year randomized controlled trial (RCT) was 59 years.

According to the authors, of the 29 patients followed for 20 years, "Twenty-one patients are alive and well. Of these, 19 have normal tests of liver function and no signs of portal hypertension."

The outcomes were then analyzed by specific treatment regimen. Of the 11 patients on methotrexate plus ursodiol, "2 died of causes unrelated to liver disease at the age of 79 and 70, and 9 are alive and well," reported the authors. All nine of these patients have normal serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and bilirubin.

Additionally, albumin levels have remained normal in eight patients; the ninth patient entered the initial trial 20 years ago with stage III biliary cirrhosis and now has a slightly decreased albumin level of 3.3 g/dL, along with portal hypertension and nonbleeding, grade 2 varices. This patient remains asymptomatic, however. Another patient receiving this regimen also developed grade 2 esophageal varices, also without bleeding.

There were 18 patients in the colchicine plus ursodiol group, and 12 were alive and well at the end of follow-up, reported the investigators. Of the remaining six, "three died of liver-unrelated causes at the age of 73, 76 and 76 respectively," wrote the authors. "They had normal biochemical tests and two had small esophageal varices at the end of the RCT."

Two patients with elevated liver enzymes at the end of the RCT underwent liver transplant; a third developed varices but was not a candidate for transplant, and died of pneumonia.

Overall, the investigators reported no treatment-related adverse events at the conclusion of follow-up.

"The results of this current study provide further evidence that combination therapy with [ursodiol], colchicine and [methotrexate] is durable and improves the natural history of primary biliary cirrhosis in a subset of primary biliary cirrhosis patients, including some who had histologically advanced liver disease at diagnosis," concluded the authors.

And while they conceded that it is impossible to determine whether the benefits were because of ursodiol, combination therapy, methotrexate, or colchicine alone, "the observations that liver function remained normal for 10 additional years and that very few patients developed portal hypertension suggests that combination therapy may have been effective."

Dr. Leung and his colleagues declared no outside funding for this study and no personal conflicts of interest.

Combination therapy consisting of ursodiol and either methotrexate or colchicine for primary biliary cirrhosis showed long-term effectiveness, lasting up to 20 years, wrote Dr. John Leung and his colleagues in the September issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2011.05.010).

Dr. Leung, of the department of gastroenterology at Tufts Medical Center, Boston, and his colleagues studied 29 patients with primary biliary cirrhosis, a chronic progressive disease thought to have an autoimmune etiology. The patients were originally part of an 85-patient, double-blind, prospective, randomized controlled trial comparing colchicine and methotrexate from 1988 to 2000, with ursodiol (ursodeoxycholic acid) added to that regimen 3 years after study initiation.

The patients examined in the current study had completed all 10 years of follow-up in the original trial. At completion, "the randomization code was broken and these 29 patients were treated according to their clinical response, personal preference, and tolerance to therapy."

They were then followed for an additional 9-13 years, either at the authors’ institution (21 patients) or via telephone calls and e-mail correspondence with referring physicians.

All patients except one were female, and the median age at the end of the initial 10-year randomized controlled trial (RCT) was 59 years.

According to the authors, of the 29 patients followed for 20 years, "Twenty-one patients are alive and well. Of these, 19 have normal tests of liver function and no signs of portal hypertension."

The outcomes were then analyzed by specific treatment regimen. Of the 11 patients on methotrexate plus ursodiol, "2 died of causes unrelated to liver disease at the age of 79 and 70, and 9 are alive and well," reported the authors. All nine of these patients have normal serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and bilirubin.

Additionally, albumin levels have remained normal in eight patients; the ninth patient entered the initial trial 20 years ago with stage III biliary cirrhosis and now has a slightly decreased albumin level of 3.3 g/dL, along with portal hypertension and nonbleeding, grade 2 varices. This patient remains asymptomatic, however. Another patient receiving this regimen also developed grade 2 esophageal varices, also without bleeding.

There were 18 patients in the colchicine plus ursodiol group, and 12 were alive and well at the end of follow-up, reported the investigators. Of the remaining six, "three died of liver-unrelated causes at the age of 73, 76 and 76 respectively," wrote the authors. "They had normal biochemical tests and two had small esophageal varices at the end of the RCT."

Two patients with elevated liver enzymes at the end of the RCT underwent liver transplant; a third developed varices but was not a candidate for transplant, and died of pneumonia.

Overall, the investigators reported no treatment-related adverse events at the conclusion of follow-up.

"The results of this current study provide further evidence that combination therapy with [ursodiol], colchicine and [methotrexate] is durable and improves the natural history of primary biliary cirrhosis in a subset of primary biliary cirrhosis patients, including some who had histologically advanced liver disease at diagnosis," concluded the authors.

And while they conceded that it is impossible to determine whether the benefits were because of ursodiol, combination therapy, methotrexate, or colchicine alone, "the observations that liver function remained normal for 10 additional years and that very few patients developed portal hypertension suggests that combination therapy may have been effective."

Dr. Leung and his colleagues declared no outside funding for this study and no personal conflicts of interest.

Combination therapy consisting of ursodiol and either methotrexate or colchicine for primary biliary cirrhosis showed long-term effectiveness, lasting up to 20 years, wrote Dr. John Leung and his colleagues in the September issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2011.05.010).

Dr. Leung, of the department of gastroenterology at Tufts Medical Center, Boston, and his colleagues studied 29 patients with primary biliary cirrhosis, a chronic progressive disease thought to have an autoimmune etiology. The patients were originally part of an 85-patient, double-blind, prospective, randomized controlled trial comparing colchicine and methotrexate from 1988 to 2000, with ursodiol (ursodeoxycholic acid) added to that regimen 3 years after study initiation.

The patients examined in the current study had completed all 10 years of follow-up in the original trial. At completion, "the randomization code was broken and these 29 patients were treated according to their clinical response, personal preference, and tolerance to therapy."

They were then followed for an additional 9-13 years, either at the authors’ institution (21 patients) or via telephone calls and e-mail correspondence with referring physicians.

All patients except one were female, and the median age at the end of the initial 10-year randomized controlled trial (RCT) was 59 years.

According to the authors, of the 29 patients followed for 20 years, "Twenty-one patients are alive and well. Of these, 19 have normal tests of liver function and no signs of portal hypertension."

The outcomes were then analyzed by specific treatment regimen. Of the 11 patients on methotrexate plus ursodiol, "2 died of causes unrelated to liver disease at the age of 79 and 70, and 9 are alive and well," reported the authors. All nine of these patients have normal serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and bilirubin.

Additionally, albumin levels have remained normal in eight patients; the ninth patient entered the initial trial 20 years ago with stage III biliary cirrhosis and now has a slightly decreased albumin level of 3.3 g/dL, along with portal hypertension and nonbleeding, grade 2 varices. This patient remains asymptomatic, however. Another patient receiving this regimen also developed grade 2 esophageal varices, also without bleeding.

There were 18 patients in the colchicine plus ursodiol group, and 12 were alive and well at the end of follow-up, reported the investigators. Of the remaining six, "three died of liver-unrelated causes at the age of 73, 76 and 76 respectively," wrote the authors. "They had normal biochemical tests and two had small esophageal varices at the end of the RCT."

Two patients with elevated liver enzymes at the end of the RCT underwent liver transplant; a third developed varices but was not a candidate for transplant, and died of pneumonia.

Overall, the investigators reported no treatment-related adverse events at the conclusion of follow-up.

"The results of this current study provide further evidence that combination therapy with [ursodiol], colchicine and [methotrexate] is durable and improves the natural history of primary biliary cirrhosis in a subset of primary biliary cirrhosis patients, including some who had histologically advanced liver disease at diagnosis," concluded the authors.

And while they conceded that it is impossible to determine whether the benefits were because of ursodiol, combination therapy, methotrexate, or colchicine alone, "the observations that liver function remained normal for 10 additional years and that very few patients developed portal hypertension suggests that combination therapy may have been effective."

Dr. Leung and his colleagues declared no outside funding for this study and no personal conflicts of interest.

A novel, fixed-dose intravenous ferric carboxymaltose regimen was more effective than was Ganzoni-calculated iron sucrose at treating iron-deficiency anemia, according to a report by Dr. Rayko Evstatiev and colleagues in the September issue of Gastroenterology.

The regimen, which included a maximum of three infusions, was well tolerated, "and the lower number of infusions increases the convenience and cost-effectiveness of intravenous iron repletion in patients with iron deficiency," wrote the authors (Gastroenterology 2011 September [doi: 10.1053/j.gastro.2011.06.005].

Dr. Evstatiev, of the Medical University of Vienna, and colleagues studied 485 patients with iron-deficiency anemia, defined as hemoglobin of 7-12 g/dL for females and 7-13 g/dL for males, along with ferritin values of less than 100 mcg/L.

All patients also had mild to moderate inflammatory bowel disease – either Crohn’s disease with a Crohn’s Disease Activity Index of less than 220 or ulcerative colitis with a Colitis Activity Index less than or equal to 7.

Exclusion criteria were administration of intravenous or oral iron treatment or blood transfusion within 4 weeks of screening, or a history of erythropoietin treatment, chronic alcohol abuse, or chronic liver disease.

Patients were randomized in a 1:1 ratio to receive either ferric carboxymaltose or the standard, individually calculated iron sucrose.

The intravenous ferric carboxymaltose, marketed as Ferinject by Vifor Pharma, the study’s sponsor, was administered in once-weekly infusions over at least 15 minutes.

In the ferric carboxymaltose group, for patients with an initial hemoglobin of greater than or equal to 10 g/dL, weighing less than 70 kg, a cumulative total dose of 1,000 mg of the drug was given; for patients weighing 70 kg or more, a total of 1,500 mg was administered.

Likewise, for patients with an initial hemoglobin of 7-10 g/dL weighing less than 70 kg, a total dose of 1,500 mg was infused. This was raised to 2,000 mg in patients weighing 70 kg or more.

Patients weighing less than 67 kg received a maximum of 500 mg per infusion, such that low-hemoglobin, low-weight patients could receive up to three total infusions, on days 1, 8, and 15. All other patients received 1,000 mg per infusion.

The iron sucrose regimen (Venofer, also from Vifor Pharma) was calculated for each patient individually by using the standard Ganzoni formula with a target hemoglobin of 15 g/dL, and included up to 11 infusions of 200 mg over at least 30 minutes, given up to twice weekly.

By week 12, an increase of hemoglobin concentration of greater than or equal to 2 g/dL was achieved in 66% of patients in the ferric carboxymaltose group, versus 54% receiving calculated iron sucrose (P = .004).

Moreover, normal hemoglobin values, defined as greater or equal to 12 g/dL in women and 13 g/dL in men, were seen in 73% of ferric carboxymaltose patients, versus 62% of iron sucrose recipients (P = .015).

Finally, the researchers also noted that normal transferrin saturation (20%-50%), normal ferritin concentration (greater than or equal to 100 mcg/L), and normal hemoglobin combined with normal ferritin were achieved significantly more often by patients in the ferric carboxymaltose group.

In a cost-effectiveness analysis, Dr. Evstatiev found that while treatment costs for the ferric carboxymaltose infusions were nearly double the price of iron sucrose per infusion, since more infusions were required among the latter group, "total treatment costs for [ferric carboxymaltose] over the whole study period were lower than those for [iron sucrose] (US$ 653 vs. US$ 891, respectively)."

Both treatment regimens were well tolerated, with the most common adverse events being nasopharyngitis and worsening of ulcerative colitis, reported the authors. No true hypersensitivity reactions were noted.

One of the authors was employed by Vifor Pharma, and others received speaker and consultancy fees from the company.

A novel, fixed-dose intravenous ferric carboxymaltose regimen was more effective than was Ganzoni-calculated iron sucrose at treating iron-deficiency anemia, according to a report by Dr. Rayko Evstatiev and colleagues in the September issue of Gastroenterology.

The regimen, which included a maximum of three infusions, was well tolerated, "and the lower number of infusions increases the convenience and cost-effectiveness of intravenous iron repletion in patients with iron deficiency," wrote the authors (Gastroenterology 2011 September [doi: 10.1053/j.gastro.2011.06.005].

Dr. Evstatiev, of the Medical University of Vienna, and colleagues studied 485 patients with iron-deficiency anemia, defined as hemoglobin of 7-12 g/dL for females and 7-13 g/dL for males, along with ferritin values of less than 100 mcg/L.

All patients also had mild to moderate inflammatory bowel disease – either Crohn’s disease with a Crohn’s Disease Activity Index of less than 220 or ulcerative colitis with a Colitis Activity Index less than or equal to 7.

Exclusion criteria were administration of intravenous or oral iron treatment or blood transfusion within 4 weeks of screening, or a history of erythropoietin treatment, chronic alcohol abuse, or chronic liver disease.

Patients were randomized in a 1:1 ratio to receive either ferric carboxymaltose or the standard, individually calculated iron sucrose.

The intravenous ferric carboxymaltose, marketed as Ferinject by Vifor Pharma, the study’s sponsor, was administered in once-weekly infusions over at least 15 minutes.

In the ferric carboxymaltose group, for patients with an initial hemoglobin of greater than or equal to 10 g/dL, weighing less than 70 kg, a cumulative total dose of 1,000 mg of the drug was given; for patients weighing 70 kg or more, a total of 1,500 mg was administered.

Likewise, for patients with an initial hemoglobin of 7-10 g/dL weighing less than 70 kg, a total dose of 1,500 mg was infused. This was raised to 2,000 mg in patients weighing 70 kg or more.

Patients weighing less than 67 kg received a maximum of 500 mg per infusion, such that low-hemoglobin, low-weight patients could receive up to three total infusions, on days 1, 8, and 15. All other patients received 1,000 mg per infusion.

The iron sucrose regimen (Venofer, also from Vifor Pharma) was calculated for each patient individually by using the standard Ganzoni formula with a target hemoglobin of 15 g/dL, and included up to 11 infusions of 200 mg over at least 30 minutes, given up to twice weekly.

By week 12, an increase of hemoglobin concentration of greater than or equal to 2 g/dL was achieved in 66% of patients in the ferric carboxymaltose group, versus 54% receiving calculated iron sucrose (P = .004).

Moreover, normal hemoglobin values, defined as greater or equal to 12 g/dL in women and 13 g/dL in men, were seen in 73% of ferric carboxymaltose patients, versus 62% of iron sucrose recipients (P = .015).

Finally, the researchers also noted that normal transferrin saturation (20%-50%), normal ferritin concentration (greater than or equal to 100 mcg/L), and normal hemoglobin combined with normal ferritin were achieved significantly more often by patients in the ferric carboxymaltose group.

In a cost-effectiveness analysis, Dr. Evstatiev found that while treatment costs for the ferric carboxymaltose infusions were nearly double the price of iron sucrose per infusion, since more infusions were required among the latter group, "total treatment costs for [ferric carboxymaltose] over the whole study period were lower than those for [iron sucrose] (US$ 653 vs. US$ 891, respectively)."

Both treatment regimens were well tolerated, with the most common adverse events being nasopharyngitis and worsening of ulcerative colitis, reported the authors. No true hypersensitivity reactions were noted.

One of the authors was employed by Vifor Pharma, and others received speaker and consultancy fees from the company.

A novel, fixed-dose intravenous ferric carboxymaltose regimen was more effective than was Ganzoni-calculated iron sucrose at treating iron-deficiency anemia, according to a report by Dr. Rayko Evstatiev and colleagues in the September issue of Gastroenterology.

The regimen, which included a maximum of three infusions, was well tolerated, "and the lower number of infusions increases the convenience and cost-effectiveness of intravenous iron repletion in patients with iron deficiency," wrote the authors (Gastroenterology 2011 September [doi: 10.1053/j.gastro.2011.06.005].

Dr. Evstatiev, of the Medical University of Vienna, and colleagues studied 485 patients with iron-deficiency anemia, defined as hemoglobin of 7-12 g/dL for females and 7-13 g/dL for males, along with ferritin values of less than 100 mcg/L.

All patients also had mild to moderate inflammatory bowel disease – either Crohn’s disease with a Crohn’s Disease Activity Index of less than 220 or ulcerative colitis with a Colitis Activity Index less than or equal to 7.

Exclusion criteria were administration of intravenous or oral iron treatment or blood transfusion within 4 weeks of screening, or a history of erythropoietin treatment, chronic alcohol abuse, or chronic liver disease.

Patients were randomized in a 1:1 ratio to receive either ferric carboxymaltose or the standard, individually calculated iron sucrose.

The intravenous ferric carboxymaltose, marketed as Ferinject by Vifor Pharma, the study’s sponsor, was administered in once-weekly infusions over at least 15 minutes.

In the ferric carboxymaltose group, for patients with an initial hemoglobin of greater than or equal to 10 g/dL, weighing less than 70 kg, a cumulative total dose of 1,000 mg of the drug was given; for patients weighing 70 kg or more, a total of 1,500 mg was administered.

Likewise, for patients with an initial hemoglobin of 7-10 g/dL weighing less than 70 kg, a total dose of 1,500 mg was infused. This was raised to 2,000 mg in patients weighing 70 kg or more.

Patients weighing less than 67 kg received a maximum of 500 mg per infusion, such that low-hemoglobin, low-weight patients could receive up to three total infusions, on days 1, 8, and 15. All other patients received 1,000 mg per infusion.

The iron sucrose regimen (Venofer, also from Vifor Pharma) was calculated for each patient individually by using the standard Ganzoni formula with a target hemoglobin of 15 g/dL, and included up to 11 infusions of 200 mg over at least 30 minutes, given up to twice weekly.

By week 12, an increase of hemoglobin concentration of greater than or equal to 2 g/dL was achieved in 66% of patients in the ferric carboxymaltose group, versus 54% receiving calculated iron sucrose (P = .004).

Moreover, normal hemoglobin values, defined as greater or equal to 12 g/dL in women and 13 g/dL in men, were seen in 73% of ferric carboxymaltose patients, versus 62% of iron sucrose recipients (P = .015).

Finally, the researchers also noted that normal transferrin saturation (20%-50%), normal ferritin concentration (greater than or equal to 100 mcg/L), and normal hemoglobin combined with normal ferritin were achieved significantly more often by patients in the ferric carboxymaltose group.

In a cost-effectiveness analysis, Dr. Evstatiev found that while treatment costs for the ferric carboxymaltose infusions were nearly double the price of iron sucrose per infusion, since more infusions were required among the latter group, "total treatment costs for [ferric carboxymaltose] over the whole study period were lower than those for [iron sucrose] (US$ 653 vs. US$ 891, respectively)."

Both treatment regimens were well tolerated, with the most common adverse events being nasopharyngitis and worsening of ulcerative colitis, reported the authors. No true hypersensitivity reactions were noted.

One of the authors was employed by Vifor Pharma, and others received speaker and consultancy fees from the company.

Despite an overall increase in the use of radioactive iodine following total thyroidectomy for primary thyroid cancer, there are still significant variations in use among institutions and across demographically different populations.

That variation, however, doesn’t appear to have had much of an impact on disease severity, according to a study published online Aug. 16 in JAMA.

"The recent increase in the incidence of small, low-risk thyroid cancer mandates an understanding of patterns of care in thyroid cancer," wrote lead author Dr. Megan R. Haymart and her colleagues (JAMA 2011;306:721-8).

Moreover, "the significant between-hospital variation in radioactive iodine use suggests clinical uncertainty about the role of radioactive iodine in thyroid cancer management."

Dr. Haymart, of the University of Michigan, Ann Arbor, and her coauthors analyzed the cases of 189,219 patients with primary thyroid cancer who underwent total thyroidectomy between 1990 and 2008. Data were culled from the National Cancer Database, which captures close to 85% of all thyroid cancers in the United States, according to the investigators.

They found that in 1990, 1,373 of 3,397 patients with the diagnosis received radioactive iodine (40%).

By 2008, that number had jumped to 11,539 of 20,620 cases (56%) – a significant increase (P less than .001).

The authors then conducted a subgroup analysis involving 85,948 patients diagnosed between 2004 and 2008, in order to "define the most contemporary practice patterns." They found that "younger age and absence of comorbidity were associated with a small but significantly greater likelihood of receiving radioactive iodine after total thyroidectomy."

Younger patients (aged 44 years and less) had an odds ratio of 2.15 for receiving the treatment compared with patients aged 60 years and older (95% confidence interval, 2.04-2.26).

Similarly, patients with a Charlson-Deyo comorbidity index score of 0 registered an OR of 1.19 for receiving radioactive iodine following thyroidectomy, compared to patients with scores of 2 or greater (95% CI, 1.07-1.35).

Factors significantly associated with a lower rate of radioactive iodine use were female sex (OR, 0.87; 95% CI, 0.84-0.91), African American race (OR, 0.83; 95% CI, 0.77-0.89), and the absence of private/government insurance (OR, 0.84; 95% CI, 0.81-0.88).

By comparison, disease severity appeared to play less of a role in treatment patterns. There was a significant difference between radioactive iodine use between American Joint Committee on Cancer designation stage I and stage IV (OR for stage I vs. stage IV, 0.34; 95% CI, 0.31-0.37). However, no difference in use existed between stage II and stage IV (OR for stage II vs. stage IV, 0.97; 95% CI, 0.88-1.07). Nor was there a significant difference in use between stage III and stage IV (OR, 1.06; 95% CI, 0.95-1.17).

The number of cases of post-thyroidectomy thyroid cancers seen at a particular institution per year also affected the use of radioactive treatment. Compared with high-volume institutions, defined as treating 35 or more cases per year, there was significantly less use of radioactive iodine at low-volume centers, treating 6 or fewer cases per year (OR, 0.44; 95% CI, 0.33-0.58) and medium-volume centers, treating 7-11 cases per year (OR, 0.62; 95% CI, 0.48-0.80).

According to Dr. Haymart and her colleagues, the conflicting use patterns are not easily explained, although some uncertainty may be due to a lack of clinical trials, as well as previous conflicting, single-institution studies. "Because of limited clinical evidence, clinical guidelines have left radioactive iodine use to physician discretion in many cases," they wrote.

"In the interest of curbing the increasing health care costs and preventing both overtreatment and undertreatment of disease, indications for radioactive iodine should be clearly defined and disease severity should become the primary driver of radioactive iodine use," they said.

The authors reported no potential conflicts of interest. The study was funded by a grant to Dr. Haymart from the National Institutes of Health.

Despite an overall increase in the use of radioactive iodine following total thyroidectomy for primary thyroid cancer, there are still significant variations in use among institutions and across demographically different populations.

That variation, however, doesn’t appear to have had much of an impact on disease severity, according to a study published online Aug. 16 in JAMA.

"The recent increase in the incidence of small, low-risk thyroid cancer mandates an understanding of patterns of care in thyroid cancer," wrote lead author Dr. Megan R. Haymart and her colleagues (JAMA 2011;306:721-8).

Moreover, "the significant between-hospital variation in radioactive iodine use suggests clinical uncertainty about the role of radioactive iodine in thyroid cancer management."

Dr. Haymart, of the University of Michigan, Ann Arbor, and her coauthors analyzed the cases of 189,219 patients with primary thyroid cancer who underwent total thyroidectomy between 1990 and 2008. Data were culled from the National Cancer Database, which captures close to 85% of all thyroid cancers in the United States, according to the investigators.

They found that in 1990, 1,373 of 3,397 patients with the diagnosis received radioactive iodine (40%).

By 2008, that number had jumped to 11,539 of 20,620 cases (56%) – a significant increase (P less than .001).

The authors then conducted a subgroup analysis involving 85,948 patients diagnosed between 2004 and 2008, in order to "define the most contemporary practice patterns." They found that "younger age and absence of comorbidity were associated with a small but significantly greater likelihood of receiving radioactive iodine after total thyroidectomy."

Younger patients (aged 44 years and less) had an odds ratio of 2.15 for receiving the treatment compared with patients aged 60 years and older (95% confidence interval, 2.04-2.26).

Similarly, patients with a Charlson-Deyo comorbidity index score of 0 registered an OR of 1.19 for receiving radioactive iodine following thyroidectomy, compared to patients with scores of 2 or greater (95% CI, 1.07-1.35).

Factors significantly associated with a lower rate of radioactive iodine use were female sex (OR, 0.87; 95% CI, 0.84-0.91), African American race (OR, 0.83; 95% CI, 0.77-0.89), and the absence of private/government insurance (OR, 0.84; 95% CI, 0.81-0.88).

By comparison, disease severity appeared to play less of a role in treatment patterns. There was a significant difference between radioactive iodine use between American Joint Committee on Cancer designation stage I and stage IV (OR for stage I vs. stage IV, 0.34; 95% CI, 0.31-0.37). However, no difference in use existed between stage II and stage IV (OR for stage II vs. stage IV, 0.97; 95% CI, 0.88-1.07). Nor was there a significant difference in use between stage III and stage IV (OR, 1.06; 95% CI, 0.95-1.17).

The number of cases of post-thyroidectomy thyroid cancers seen at a particular institution per year also affected the use of radioactive treatment. Compared with high-volume institutions, defined as treating 35 or more cases per year, there was significantly less use of radioactive iodine at low-volume centers, treating 6 or fewer cases per year (OR, 0.44; 95% CI, 0.33-0.58) and medium-volume centers, treating 7-11 cases per year (OR, 0.62; 95% CI, 0.48-0.80).

According to Dr. Haymart and her colleagues, the conflicting use patterns are not easily explained, although some uncertainty may be due to a lack of clinical trials, as well as previous conflicting, single-institution studies. "Because of limited clinical evidence, clinical guidelines have left radioactive iodine use to physician discretion in many cases," they wrote.

"In the interest of curbing the increasing health care costs and preventing both overtreatment and undertreatment of disease, indications for radioactive iodine should be clearly defined and disease severity should become the primary driver of radioactive iodine use," they said.

The authors reported no potential conflicts of interest. The study was funded by a grant to Dr. Haymart from the National Institutes of Health.

Despite an overall increase in the use of radioactive iodine following total thyroidectomy for primary thyroid cancer, there are still significant variations in use among institutions and across demographically different populations.

That variation, however, doesn’t appear to have had much of an impact on disease severity, according to a study published online Aug. 16 in JAMA.

"The recent increase in the incidence of small, low-risk thyroid cancer mandates an understanding of patterns of care in thyroid cancer," wrote lead author Dr. Megan R. Haymart and her colleagues (JAMA 2011;306:721-8).

Moreover, "the significant between-hospital variation in radioactive iodine use suggests clinical uncertainty about the role of radioactive iodine in thyroid cancer management."

Dr. Haymart, of the University of Michigan, Ann Arbor, and her coauthors analyzed the cases of 189,219 patients with primary thyroid cancer who underwent total thyroidectomy between 1990 and 2008. Data were culled from the National Cancer Database, which captures close to 85% of all thyroid cancers in the United States, according to the investigators.

They found that in 1990, 1,373 of 3,397 patients with the diagnosis received radioactive iodine (40%).

By 2008, that number had jumped to 11,539 of 20,620 cases (56%) – a significant increase (P less than .001).

The authors then conducted a subgroup analysis involving 85,948 patients diagnosed between 2004 and 2008, in order to "define the most contemporary practice patterns." They found that "younger age and absence of comorbidity were associated with a small but significantly greater likelihood of receiving radioactive iodine after total thyroidectomy."

Younger patients (aged 44 years and less) had an odds ratio of 2.15 for receiving the treatment compared with patients aged 60 years and older (95% confidence interval, 2.04-2.26).

Similarly, patients with a Charlson-Deyo comorbidity index score of 0 registered an OR of 1.19 for receiving radioactive iodine following thyroidectomy, compared to patients with scores of 2 or greater (95% CI, 1.07-1.35).

Factors significantly associated with a lower rate of radioactive iodine use were female sex (OR, 0.87; 95% CI, 0.84-0.91), African American race (OR, 0.83; 95% CI, 0.77-0.89), and the absence of private/government insurance (OR, 0.84; 95% CI, 0.81-0.88).

By comparison, disease severity appeared to play less of a role in treatment patterns. There was a significant difference between radioactive iodine use between American Joint Committee on Cancer designation stage I and stage IV (OR for stage I vs. stage IV, 0.34; 95% CI, 0.31-0.37). However, no difference in use existed between stage II and stage IV (OR for stage II vs. stage IV, 0.97; 95% CI, 0.88-1.07). Nor was there a significant difference in use between stage III and stage IV (OR, 1.06; 95% CI, 0.95-1.17).

The number of cases of post-thyroidectomy thyroid cancers seen at a particular institution per year also affected the use of radioactive treatment. Compared with high-volume institutions, defined as treating 35 or more cases per year, there was significantly less use of radioactive iodine at low-volume centers, treating 6 or fewer cases per year (OR, 0.44; 95% CI, 0.33-0.58) and medium-volume centers, treating 7-11 cases per year (OR, 0.62; 95% CI, 0.48-0.80).

According to Dr. Haymart and her colleagues, the conflicting use patterns are not easily explained, although some uncertainty may be due to a lack of clinical trials, as well as previous conflicting, single-institution studies. "Because of limited clinical evidence, clinical guidelines have left radioactive iodine use to physician discretion in many cases," they wrote.

"In the interest of curbing the increasing health care costs and preventing both overtreatment and undertreatment of disease, indications for radioactive iodine should be clearly defined and disease severity should become the primary driver of radioactive iodine use," they said.

The authors reported no potential conflicts of interest. The study was funded by a grant to Dr. Haymart from the National Institutes of Health.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

A once-daily, oral, fixed dose of the Factor Xa inhibitor rivaroxaban was noninferior to warfarin for the prevention of stroke in patients with atrial fibrillation in a randomized, double-blind trial.

Moreover, although rates of bleeding were similar between the two groups of patients, "bleeding that proved fatal or involved a critical anatomical site occurred less frequently in the rivaroxaban group," Dr. Manesh R. Patel of Duke University, Durham, N.C., and his coauthors wrote online Aug. 10 in the New England Journal of Medicine.

"In contrast, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group."

In July, the U.S. Food and Drug Administration approved rivaroxaban (Xarelto) for the prevention of deep vein thrombosis.

The investigators enrolled 14,264 patients with elevated stroke risk from 1,178 sites in 45 countries with nonvalvular atrial fibrillation (AF). An "elevated risk" was indicated by a previous stroke history, transient ischemic attack, or systemic embolism. Johnson & Johnson and Bayer Healthcare, the U.S. and European marketers of the drug, respectively, sponsored the study, called ROCKET AF (Rivaroxaban One Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).

Patients also were included if they had at least two of several risk factors, including heart failure, an ejection fraction of less than 35%, hypertension, age older than 75 years, or diabetes mellitus.

The median age of participants was 73 years, of whom nearly 40% were women. Both groups were statistically similar or identical in terms of body mass index, median systolic and diastolic blood pressure, type of AF (persistent, paroxysmal, or new-onset), and other related factors.

Patients were randomly assigned to receive either a once-daily, 20-mg dose of rivaroxaban or a standard, adjusted dose of warfarin, with a target international normalized ratio (INR) of 2-3. Patients in the rivaroxaban group who had a creatinine clearance of 30-49 mL/min received a 15-mg dose. All patients also received a placebo tablet (N. Engl. J. Med. 2011 Aug. 10 [doi:10.1056/NEJMoa1009638]).

The patients underwent treatment for a median of 590 days and had a median follow-up period of 707 days. Among the patients who received at least one dose of a study drug and had no major protocol violation, the rate of stroke or embolism was 1.7% per year for rivaroxaban, compared with 2.2% per year for warfarin. Overall, stroke or embolism occurred in 188 rivaroxaban patients and 241 warfarin patients, for a hazard ratio of 0.79 among rivaroxaban recipients (95% confidence interval, 0.66-0.96, P < .001 for noninferiority).

The rate of "major" bleeding was similar between the rivaroxaban and warfarin groups (3.6% vs. 3.4%, respectively). Major bleeding was defined as "clinically overt" bleeding associated with fatal outcome; involvement with a "critical" site including intracranial, spinal, ocular, pericardial, articular, retroperitoneal, or intramuscular areas; a drop in hemoglobin of 2 g/dL or greater; transfusion of multiple units of blood; or permanent disability.

Rates of "clinically relevant non-major bleeding" also were similar, occurring in 1,475 rivaroxaban patients and 1,449 warfarin patients (14.9% vs. 14.5%, respectively; rivaroxaban hazard ratio of 1.03; P = .44). Non-major events included overt bleeds not meeting major criteria, but requiring physician intervention.

However, rivaroxaban users were more likely to experience drops in hemoglobin of 2 g/dL or more, compared with warfarin users (2.8% vs. 2.3%, respectively; P = .02), as well as gastrointestinal bleeding (3.2% vs. 2.2%, respectively; P less than .001).

On the other hand, warfarin-treated patients more frequently experienced fatal bleeding (0.2% for rivaroxaban versus 0.5% for warfarin, P = .003) and intracranial bleeding (0.5% for rivaroxaban, versus 0.7% for warfarin, P =0.02). The target INR was maintained only 55% of the time in patients who received warfarin, the authors noted.

In addition to the study funding, Dr. Patel and several other authors of the study disclosed numerous financial relationships to pharmaceutical companies, including the makers of rivaroxaban; several authors were also employees of Johnson & Johnson as well as Bayer Healthcare.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, according to a report by Dr. Melena D. Bellin and colleagues in the September issue of Clinical Gastroenterology and Hepatology.

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

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

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

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

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

At baseline, all patients required narcotics, either on a daily basis (n = 13) or intermittently. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. Seven patients also had undergone prior pancreatic surgery at outside institutions.

"Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34," wrote Dr. Bellin. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50 (P less than .001). Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance (P = .06). Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely.

"Of the remaining 5 patients, 2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose," they added.

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use; all of them had hemoglobin A_1c levels less than or equal to 6.5%.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin-dependent (P = .04) and to have variable HbA_1c levels, perhaps necessitating "a paradigm shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures," recommended Dr. Bellin.

"Although optimal timing of surgery needs to be elucidated, for those who will go on to [total pancreatectomy with islet autotransplantation], earlier surgery may avoid progressive damage to the endocrine pancreas and the hyperalgesia associated with chronic narcotic use," concluded Dr. Bellin.

The authors reported no individual conflicts of interest related to this study, which was supported in part by the National Pancreas Foundation.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, according to a report by Dr. Melena D. Bellin and colleagues in the September issue of Clinical Gastroenterology and Hepatology.

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

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

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

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

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

At baseline, all patients required narcotics, either on a daily basis (n = 13) or intermittently. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. Seven patients also had undergone prior pancreatic surgery at outside institutions.

"Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34," wrote Dr. Bellin. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50 (P less than .001). Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance (P = .06). Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely.

"Of the remaining 5 patients, 2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose," they added.

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use; all of them had hemoglobin A_1c levels less than or equal to 6.5%.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin-dependent (P = .04) and to have variable HbA_1c levels, perhaps necessitating "a paradigm shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures," recommended Dr. Bellin.

"Although optimal timing of surgery needs to be elucidated, for those who will go on to [total pancreatectomy with islet autotransplantation], earlier surgery may avoid progressive damage to the endocrine pancreas and the hyperalgesia associated with chronic narcotic use," concluded Dr. Bellin.

The authors reported no individual conflicts of interest related to this study, which was supported in part by the National Pancreas Foundation.

Total pancreatectomy with islet autotransplant in pediatric chronic pancreatitis significantly improves quality of life and largely obviates the need for narcotics post procedure, according to a report by Dr. Melena D. Bellin and colleagues in the September issue of Clinical Gastroenterology and Hepatology.

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

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

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

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

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

At baseline, all patients required narcotics, either on a daily basis (n = 13) or intermittently. All patients had also had multiple hospitalizations for pain management. Two were dependent on jejunal tube feedings and two on total parenteral nutrition. Seven patients also had undergone prior pancreatic surgery at outside institutions.

"Prior to surgery, all patients had below average HRQOL [health related quality of life] based on the SF-36, with a mean PCS score of 30 and a mean MCS score of 34," wrote Dr. Bellin. These scores were equivalent to 2 and 1.5 standard deviations, respectively, below the norm for the U.S. population.

By 1 year, wrote the authors, the PCS improved significantly, to a mean of 50 (P less than .001). Similarly, the MCS improved to a mean of 46, although the increase just missed statistical significance (P = .06). Both postsurgery scores were equivalent to normal HRQOL values in this population.

Looking at postprocedure narcotics use, the authors found that by 1 year, 14 patients had stopped using narcotics for pain management entirely.

"Of the remaining 5 patients, 2 reported rare narcotic use (a few times a year), 1 used tramadol, and 2 used daily narcotics at a reduced dose," they added.

After surgery, all of the patients received insulin initially, with a goal of weaning them off insulin if possible. At a mean of 18 months following the islet graft, seven patients were insulin independent, and four more were reporting minimal insulin use; all of them had hemoglobin A_1c levels less than or equal to 6.5%.

However, the study showed that patients who had undergone prior drainage procedures were more likely to be insulin-dependent (P = .04) and to have variable HbA_1c levels, perhaps necessitating "a paradigm shift in the current management of CP, with avoidance of partial resections without islet autotransplantation and of surgical drainage procedures," recommended Dr. Bellin.

"Although optimal timing of surgery needs to be elucidated, for those who will go on to [total pancreatectomy with islet autotransplantation], earlier surgery may avoid progressive damage to the endocrine pancreas and the hyperalgesia associated with chronic narcotic use," concluded Dr. Bellin.

The authors reported no individual conflicts of interest related to this study, which was supported in part by the National Pancreas Foundation.

Radiographic response to locoregional embolization of hepatocellular carcinoma predicted survival, Dr. Khairuddin Memon and colleagues reported in the August issue of Gastroenterology.

The finding is the first to substantiate the prognostic value of tumor response to chemoembolization and radioembolization in hepatocellular carcinoma (HCC), they wrote (Gastroenterology 2011 August [doi: 10.1053/j.gastro.2011.04.054].

"Based on these findings, consideration should be made to develop treatments for HCC that not only prolong [time to progression], but also elicit radiographic tumor response," added Dr. Memon of the department of radiology at Northwestern Memorial Hospital in Chicago.

According to Dr. Memon, between 2000 and 2008, 463 patients with HCC were treated at the authors’ institution using transarterial locoregional therapies – either transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y). All of these patients had unresectable HCC and bilirubin levels less than 3.0 mg/dL.

For the present analysis, the authors subsequently excluded all patients who underwent transplant, exhibited portal venous thrombosis or extrahepatic metastases at baseline, or had a Child-Pugh score greater than B7.

Survival outcomes were analyzed for the remaining 159 patients with respect to their response to TACE or Y therapy. Most of the patients (74%) were male, and 40% were younger than 65 years of age.

Response status was assessed using both World Health Organization criteria and European Association for Study of the Liver (EASL) guidelines. Patients were assessed using computed tomography or magnetic resonance imaging at 1 month after treatment and then at scheduled 2- to 3-month intervals.

The authors found that patients who were responders at the 6-month posttreatment landmark according to WHO criteria had an overall median survival of 31.6 months, compared with 13.7 months for 6-month WHO nonresponders (P = .069).

Judging by EASL guidelines, however, the difference reached significance: 6-month landmark EASL responders had a median overall survival of 24.6 months, versus 13.2 months for nonresponders (P = .002).

Highly significant differences were found when the participants were divided into two groups based on response or nonresponse at 12 months. By WHO criteria, median overall survival for responders at 12 months was 36.4 months, versus 11.1 months for nonresponders (P = .004). And by EASL standards, median survival was also 36.4 months for responders, versus 9.7 months for nonresponders (P less than .0001).

The authors also analyzed risk of death in the 6 months following each landmark. They found that WHO responders at the 6-month landmark had a 6.6% rate of death in this window, versus 15.5% among nonresponders – a nonsignificant difference (P = .707).

However, according to EASL standards, the rate of death in the 6 months following the 6-month landmark was 4.7% among responders versus 20.6% among nonresponders (P = .046).

Moreover, the death rate in the 6 months following the 12-month landmark was 0% for WHO responders, versus 31.5% for nonresponders (P = .010), and it was 4% and 32.7%, respectively, by EASL guidelines (P = .013).

The authors added that baseline tumor size was not a significant factor affecting survival in a univariate analysis.

"Our data show that responders by WHO/EASL criteria live longer than nonresponders from the landmark onwards, with the exception of WHO 6-month landmark (near significance); the trend is clear," wrote the authors.

Randomized controlled trials "will be required to validate this concept and establish radiographic response as a surrogate of the true end point (survival)."

Dr. Memon and his fellow researchers declared no conflicts of interest associated with this study.

Radiographic response to locoregional embolization of hepatocellular carcinoma predicted survival, Dr. Khairuddin Memon and colleagues reported in the August issue of Gastroenterology.

The finding is the first to substantiate the prognostic value of tumor response to chemoembolization and radioembolization in hepatocellular carcinoma (HCC), they wrote (Gastroenterology 2011 August [doi: 10.1053/j.gastro.2011.04.054].

"Based on these findings, consideration should be made to develop treatments for HCC that not only prolong [time to progression], but also elicit radiographic tumor response," added Dr. Memon of the department of radiology at Northwestern Memorial Hospital in Chicago.

According to Dr. Memon, between 2000 and 2008, 463 patients with HCC were treated at the authors’ institution using transarterial locoregional therapies – either transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y). All of these patients had unresectable HCC and bilirubin levels less than 3.0 mg/dL.

For the present analysis, the authors subsequently excluded all patients who underwent transplant, exhibited portal venous thrombosis or extrahepatic metastases at baseline, or had a Child-Pugh score greater than B7.

Survival outcomes were analyzed for the remaining 159 patients with respect to their response to TACE or Y therapy. Most of the patients (74%) were male, and 40% were younger than 65 years of age.

Response status was assessed using both World Health Organization criteria and European Association for Study of the Liver (EASL) guidelines. Patients were assessed using computed tomography or magnetic resonance imaging at 1 month after treatment and then at scheduled 2- to 3-month intervals.

The authors found that patients who were responders at the 6-month posttreatment landmark according to WHO criteria had an overall median survival of 31.6 months, compared with 13.7 months for 6-month WHO nonresponders (P = .069).

Judging by EASL guidelines, however, the difference reached significance: 6-month landmark EASL responders had a median overall survival of 24.6 months, versus 13.2 months for nonresponders (P = .002).

Highly significant differences were found when the participants were divided into two groups based on response or nonresponse at 12 months. By WHO criteria, median overall survival for responders at 12 months was 36.4 months, versus 11.1 months for nonresponders (P = .004). And by EASL standards, median survival was also 36.4 months for responders, versus 9.7 months for nonresponders (P less than .0001).

The authors also analyzed risk of death in the 6 months following each landmark. They found that WHO responders at the 6-month landmark had a 6.6% rate of death in this window, versus 15.5% among nonresponders – a nonsignificant difference (P = .707).

However, according to EASL standards, the rate of death in the 6 months following the 6-month landmark was 4.7% among responders versus 20.6% among nonresponders (P = .046).

Moreover, the death rate in the 6 months following the 12-month landmark was 0% for WHO responders, versus 31.5% for nonresponders (P = .010), and it was 4% and 32.7%, respectively, by EASL guidelines (P = .013).

The authors added that baseline tumor size was not a significant factor affecting survival in a univariate analysis.

"Our data show that responders by WHO/EASL criteria live longer than nonresponders from the landmark onwards, with the exception of WHO 6-month landmark (near significance); the trend is clear," wrote the authors.

Randomized controlled trials "will be required to validate this concept and establish radiographic response as a surrogate of the true end point (survival)."

Dr. Memon and his fellow researchers declared no conflicts of interest associated with this study.

Radiographic response to locoregional embolization of hepatocellular carcinoma predicted survival, Dr. Khairuddin Memon and colleagues reported in the August issue of Gastroenterology.

The finding is the first to substantiate the prognostic value of tumor response to chemoembolization and radioembolization in hepatocellular carcinoma (HCC), they wrote (Gastroenterology 2011 August [doi: 10.1053/j.gastro.2011.04.054].

"Based on these findings, consideration should be made to develop treatments for HCC that not only prolong [time to progression], but also elicit radiographic tumor response," added Dr. Memon of the department of radiology at Northwestern Memorial Hospital in Chicago.

According to Dr. Memon, between 2000 and 2008, 463 patients with HCC were treated at the authors’ institution using transarterial locoregional therapies – either transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y). All of these patients had unresectable HCC and bilirubin levels less than 3.0 mg/dL.

For the present analysis, the authors subsequently excluded all patients who underwent transplant, exhibited portal venous thrombosis or extrahepatic metastases at baseline, or had a Child-Pugh score greater than B7.

Survival outcomes were analyzed for the remaining 159 patients with respect to their response to TACE or Y therapy. Most of the patients (74%) were male, and 40% were younger than 65 years of age.

Response status was assessed using both World Health Organization criteria and European Association for Study of the Liver (EASL) guidelines. Patients were assessed using computed tomography or magnetic resonance imaging at 1 month after treatment and then at scheduled 2- to 3-month intervals.

The authors found that patients who were responders at the 6-month posttreatment landmark according to WHO criteria had an overall median survival of 31.6 months, compared with 13.7 months for 6-month WHO nonresponders (P = .069).

Judging by EASL guidelines, however, the difference reached significance: 6-month landmark EASL responders had a median overall survival of 24.6 months, versus 13.2 months for nonresponders (P = .002).

Highly significant differences were found when the participants were divided into two groups based on response or nonresponse at 12 months. By WHO criteria, median overall survival for responders at 12 months was 36.4 months, versus 11.1 months for nonresponders (P = .004). And by EASL standards, median survival was also 36.4 months for responders, versus 9.7 months for nonresponders (P less than .0001).

The authors also analyzed risk of death in the 6 months following each landmark. They found that WHO responders at the 6-month landmark had a 6.6% rate of death in this window, versus 15.5% among nonresponders – a nonsignificant difference (P = .707).

However, according to EASL standards, the rate of death in the 6 months following the 6-month landmark was 4.7% among responders versus 20.6% among nonresponders (P = .046).

Moreover, the death rate in the 6 months following the 12-month landmark was 0% for WHO responders, versus 31.5% for nonresponders (P = .010), and it was 4% and 32.7%, respectively, by EASL guidelines (P = .013).

The authors added that baseline tumor size was not a significant factor affecting survival in a univariate analysis.

"Our data show that responders by WHO/EASL criteria live longer than nonresponders from the landmark onwards, with the exception of WHO 6-month landmark (near significance); the trend is clear," wrote the authors.

Randomized controlled trials "will be required to validate this concept and establish radiographic response as a surrogate of the true end point (survival)."

Dr. Memon and his fellow researchers declared no conflicts of interest associated with this study.

Patients with nonalcoholic steatohepatitis who were deemed candidates for liver transplant were less likely to actually undergo the procedure than were candidates with hepatitis C, and more often died or were delisted for being too ill before transplant, wrote Dr. Jacqueline G. O’Leary and colleagues in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, the study showed that the presence of comorbid conditions such as hypertension and obesity was the predominant reason for denial of liver transplant in nonalcoholic steatohepatitis (NASH).

The findings mean that "The primary focus of treatment in NASH/CC [cryptogenic cirrhosis] patients with a low MELD [model for end-stage liver disease] score needs to be aggressive treatment of their obesity, diabetes, lipid disorders, and hypertension so that they do not develop comorbid conditions that cause death or make them ineligible for transplant."

Dr. O’Leary, of the Annette C. and Harold C. Simmons Transplant Institute at the Baylor University Medical Center at Dallas, studied data from 415 patients with NASH and/or CC and 1,232 patients with hepatitis C virus (HCV)–associated cirrhosis who were evaluated for transplant at the Baylor facility (Clin. Gastroenterol Hepatol. 2011 [doi.10.1016/j.cgh.2011.04.007]).

All NASH/CC patients denied for transplant were compared to all HCV patients denied for transplant. "When patients are denied for OLT [orthotopic liver transplantation], they are recorded as excluded for medical comorbidities, psychosocial reasons, adequate hepatic reserve, exceeding tumor criteria, or death," wrote the investigators. "However, the specific comorbidities and psychosocial reasons are not recorded in our database."

Overall, Dr. O’Leary found that 197 NASH/CC patients were denied for listing (47%), as were 586 HCV patients (48%).

In general, the NASH/CC patients with denials were older (median age 60 years vs. 51 years; P less than .001), more likely to be female (57% vs. 35%; P less than .001), heavier (body mass index greater than 30 kg/m²: 59% vs. 40%; P less than .001), and had a lower glomerular filtration rate (74 mL/min vs. 88 mL/min; P = .004), compared with the HCV patients who were denied.

According to the analysis, among the NASH/CC patients, the existence of comorbid conditions was the most likely reason for denial (72% vs. 27% in the HCV group), whereas among the HCV patients, ongoing psychological issues – including recidivism and lack of social support – precluded the greatest percentage of candidates from transplant (39% vs. 8% in the NASH/CC cohort).

Among all denied patients, liver disease severity was similar for the two groups, with MELD scores of 12 among NASH/CC patients versus 11 for HCV patients.

The authors also compared the 217 NASH/CC patients who were listed for transplant with the 645 HCV patients who were listed.

NASH/CC patients were heavier (BMI greater than 30: 54% vs. 42%; P = .004), and were more likely to have diabetes (55% vs. 22%; P less than .001) and hypertension (46% vs. 28%; P less than .001) than the HCV patients. Liver disease severity, as measured by median MELD score (14 for both) and Child-Turcotte-Pugh point system (7 for both), was the same.

However, the authors found that among those listed, patients with NASH/CC were significantly less likely to ultimately be transplanted than patients with HCV (48% vs. 62%; P less than .001).

"While listed, 22% of NASH/CC patients and 16% of HCV patients either died on the list or were delisted for being too ill," the authors explained

"Although some have suggested that NASH cirrhosis would overtake HCV as the main indication for [transplant] by 2020, this does not seem likely, since coincident comorbid conditions often found in NASH/CC patients may often preclude [transplant]," wrote the authors.

"In fact, our data confirm this suspicion; NASH/CC patients were almost twice as likely as HCV cirrhosis patients to be denied for listing because of comorbid conditions."

The authors reported no grant support and no relevant conflicts of interest.

Patients with nonalcoholic steatohepatitis who were deemed candidates for liver transplant were less likely to actually undergo the procedure than were candidates with hepatitis C, and more often died or were delisted for being too ill before transplant, wrote Dr. Jacqueline G. O’Leary and colleagues in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, the study showed that the presence of comorbid conditions such as hypertension and obesity was the predominant reason for denial of liver transplant in nonalcoholic steatohepatitis (NASH).

The findings mean that "The primary focus of treatment in NASH/CC [cryptogenic cirrhosis] patients with a low MELD [model for end-stage liver disease] score needs to be aggressive treatment of their obesity, diabetes, lipid disorders, and hypertension so that they do not develop comorbid conditions that cause death or make them ineligible for transplant."

Dr. O’Leary, of the Annette C. and Harold C. Simmons Transplant Institute at the Baylor University Medical Center at Dallas, studied data from 415 patients with NASH and/or CC and 1,232 patients with hepatitis C virus (HCV)–associated cirrhosis who were evaluated for transplant at the Baylor facility (Clin. Gastroenterol Hepatol. 2011 [doi.10.1016/j.cgh.2011.04.007]).

All NASH/CC patients denied for transplant were compared to all HCV patients denied for transplant. "When patients are denied for OLT [orthotopic liver transplantation], they are recorded as excluded for medical comorbidities, psychosocial reasons, adequate hepatic reserve, exceeding tumor criteria, or death," wrote the investigators. "However, the specific comorbidities and psychosocial reasons are not recorded in our database."

Overall, Dr. O’Leary found that 197 NASH/CC patients were denied for listing (47%), as were 586 HCV patients (48%).

In general, the NASH/CC patients with denials were older (median age 60 years vs. 51 years; P less than .001), more likely to be female (57% vs. 35%; P less than .001), heavier (body mass index greater than 30 kg/m²: 59% vs. 40%; P less than .001), and had a lower glomerular filtration rate (74 mL/min vs. 88 mL/min; P = .004), compared with the HCV patients who were denied.

According to the analysis, among the NASH/CC patients, the existence of comorbid conditions was the most likely reason for denial (72% vs. 27% in the HCV group), whereas among the HCV patients, ongoing psychological issues – including recidivism and lack of social support – precluded the greatest percentage of candidates from transplant (39% vs. 8% in the NASH/CC cohort).

Among all denied patients, liver disease severity was similar for the two groups, with MELD scores of 12 among NASH/CC patients versus 11 for HCV patients.

The authors also compared the 217 NASH/CC patients who were listed for transplant with the 645 HCV patients who were listed.

NASH/CC patients were heavier (BMI greater than 30: 54% vs. 42%; P = .004), and were more likely to have diabetes (55% vs. 22%; P less than .001) and hypertension (46% vs. 28%; P less than .001) than the HCV patients. Liver disease severity, as measured by median MELD score (14 for both) and Child-Turcotte-Pugh point system (7 for both), was the same.

However, the authors found that among those listed, patients with NASH/CC were significantly less likely to ultimately be transplanted than patients with HCV (48% vs. 62%; P less than .001).

"While listed, 22% of NASH/CC patients and 16% of HCV patients either died on the list or were delisted for being too ill," the authors explained

"Although some have suggested that NASH cirrhosis would overtake HCV as the main indication for [transplant] by 2020, this does not seem likely, since coincident comorbid conditions often found in NASH/CC patients may often preclude [transplant]," wrote the authors.

"In fact, our data confirm this suspicion; NASH/CC patients were almost twice as likely as HCV cirrhosis patients to be denied for listing because of comorbid conditions."

The authors reported no grant support and no relevant conflicts of interest.

Patients with nonalcoholic steatohepatitis who were deemed candidates for liver transplant were less likely to actually undergo the procedure than were candidates with hepatitis C, and more often died or were delisted for being too ill before transplant, wrote Dr. Jacqueline G. O’Leary and colleagues in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, the study showed that the presence of comorbid conditions such as hypertension and obesity was the predominant reason for denial of liver transplant in nonalcoholic steatohepatitis (NASH).

The findings mean that "The primary focus of treatment in NASH/CC [cryptogenic cirrhosis] patients with a low MELD [model for end-stage liver disease] score needs to be aggressive treatment of their obesity, diabetes, lipid disorders, and hypertension so that they do not develop comorbid conditions that cause death or make them ineligible for transplant."

Dr. O’Leary, of the Annette C. and Harold C. Simmons Transplant Institute at the Baylor University Medical Center at Dallas, studied data from 415 patients with NASH and/or CC and 1,232 patients with hepatitis C virus (HCV)–associated cirrhosis who were evaluated for transplant at the Baylor facility (Clin. Gastroenterol Hepatol. 2011 [doi.10.1016/j.cgh.2011.04.007]).

All NASH/CC patients denied for transplant were compared to all HCV patients denied for transplant. "When patients are denied for OLT [orthotopic liver transplantation], they are recorded as excluded for medical comorbidities, psychosocial reasons, adequate hepatic reserve, exceeding tumor criteria, or death," wrote the investigators. "However, the specific comorbidities and psychosocial reasons are not recorded in our database."

Overall, Dr. O’Leary found that 197 NASH/CC patients were denied for listing (47%), as were 586 HCV patients (48%).

In general, the NASH/CC patients with denials were older (median age 60 years vs. 51 years; P less than .001), more likely to be female (57% vs. 35%; P less than .001), heavier (body mass index greater than 30 kg/m²: 59% vs. 40%; P less than .001), and had a lower glomerular filtration rate (74 mL/min vs. 88 mL/min; P = .004), compared with the HCV patients who were denied.

According to the analysis, among the NASH/CC patients, the existence of comorbid conditions was the most likely reason for denial (72% vs. 27% in the HCV group), whereas among the HCV patients, ongoing psychological issues – including recidivism and lack of social support – precluded the greatest percentage of candidates from transplant (39% vs. 8% in the NASH/CC cohort).

Among all denied patients, liver disease severity was similar for the two groups, with MELD scores of 12 among NASH/CC patients versus 11 for HCV patients.

The authors also compared the 217 NASH/CC patients who were listed for transplant with the 645 HCV patients who were listed.

NASH/CC patients were heavier (BMI greater than 30: 54% vs. 42%; P = .004), and were more likely to have diabetes (55% vs. 22%; P less than .001) and hypertension (46% vs. 28%; P less than .001) than the HCV patients. Liver disease severity, as measured by median MELD score (14 for both) and Child-Turcotte-Pugh point system (7 for both), was the same.

However, the authors found that among those listed, patients with NASH/CC were significantly less likely to ultimately be transplanted than patients with HCV (48% vs. 62%; P less than .001).

"While listed, 22% of NASH/CC patients and 16% of HCV patients either died on the list or were delisted for being too ill," the authors explained

"Although some have suggested that NASH cirrhosis would overtake HCV as the main indication for [transplant] by 2020, this does not seem likely, since coincident comorbid conditions often found in NASH/CC patients may often preclude [transplant]," wrote the authors.

"In fact, our data confirm this suspicion; NASH/CC patients were almost twice as likely as HCV cirrhosis patients to be denied for listing because of comorbid conditions."

The authors reported no grant support and no relevant conflicts of interest.

At 3 years, radiofrequency ablation for dysplastic Barrett’s esophagus resulted in complete eradication of dysplasia in 98% of patients, Dr. Nicholas J. Shaheen and colleagues reported in the August issue of Gastroenterology.

The finding represents the latest results from the Ablation of Intestinal Metaplasia Containing Dysplasia Study (AIM Dysplasia Study). The study’s 12-month results were published by Dr. Shaheen and colleagues in 2009 (N. Engl. J. Med. 2009;360:2277-88).

According to Dr. Shaheen, director of the center for esophageal diseases and swallowing at the University of North Carolina, Chapel Hill, the original study recruited 127 patients aged 18-80 years with nonnodular Barrett’s esophagus less than or equal to 8 cm in length.

Patients were randomized in a 2:1 ratio to either radiofrequency ablation (n = 84) or endoscopic surveillance – simple endoscopy with no treatment, the sham arm (n = 43). In the current follow-up, Dr. Shaheen and his colleagues reported on the durability of the treatment at 2 and 3 years post ablation Gastroenterology 2011 August [doi:10.1053/j.gastro.2011.04.061]).

"After completion of the 12-month assessment, subjects in the sham arm were offered crossover to active (RFA) treatment," wrote the investigators. All 35 of the original 43 sham subjects who were eligible for crossover elected to receive treatment (4 had developed esophageal adenocarcinoma while in the sham arm prior to the 1 year end point, and 4 were lost to follow-up). All treated subjects were then followed for 2 years after receiving RFA therapy.

Overall, 119 subjects underwent ablation (84 at study outset plus 35 crossovers), with 106 completing at least the 2-year follow-up. At 2 years, 101 of 106 (95%) of subjects had complete eradication of dysplasia, and 99 of 106 (93%) had complete eradication of intestinal metaplasia, the authors reported. However, over the mean follow-up period of 3.05 years, 25 subjects required an interim focal treatment of recurrent Barrett’s. Moreover, "in the most stringent analysis, if we include any subject who ever received any RFA and left the trial before the 2 year end point as a failure (n = 13), the response rates were 101/119 (85%)" for complete eradication of dysplasia and 99 of 119 (83%) for complete eradication of intestinal metaplasia, the authors added.

Among the 56 subjects for whom 3-year follow-up data were available, 55 (98%) had complete eradication of dysplasia and 51 (91%) had complete eradication of intestinal metaplasia. The annual rate of any neoplastic progression was 1.37% per patient-year, or 1/73 patient-years.

Four serious adverse events have occurred to date in the 119 subjects (3.4%): one upper gastrointestinal bleed in a patient on dual aspirin and clopidogrel therapy for heart disease; one episode of chest pain occurring 8 days following ablation; and two overnight hospitalizations for nausea and chest pain immediately following the procedure.

"The main adverse side effect was stricture occurrence, which occurred in 7.6% of subjects and was correctable with a mean of 2.8 dilation sessions," the investigators wrote. There were no perforations or procedure-related deaths.

Radiofrequency ablation in this study was accomplished with a device made by BÂRRX Medical, which supported both the 2009 study and the current follow-up. Several investigators also reported financial relationships with BÂRRX Medical, among other pharmaceutical makers. AstraZeneca supplied esomeprazole for the patients through the company’s investigator-sponsored study program.

At 3 years, radiofrequency ablation for dysplastic Barrett’s esophagus resulted in complete eradication of dysplasia in 98% of patients, Dr. Nicholas J. Shaheen and colleagues reported in the August issue of Gastroenterology.

The finding represents the latest results from the Ablation of Intestinal Metaplasia Containing Dysplasia Study (AIM Dysplasia Study). The study’s 12-month results were published by Dr. Shaheen and colleagues in 2009 (N. Engl. J. Med. 2009;360:2277-88).

According to Dr. Shaheen, director of the center for esophageal diseases and swallowing at the University of North Carolina, Chapel Hill, the original study recruited 127 patients aged 18-80 years with nonnodular Barrett’s esophagus less than or equal to 8 cm in length.

Patients were randomized in a 2:1 ratio to either radiofrequency ablation (n = 84) or endoscopic surveillance – simple endoscopy with no treatment, the sham arm (n = 43). In the current follow-up, Dr. Shaheen and his colleagues reported on the durability of the treatment at 2 and 3 years post ablation Gastroenterology 2011 August [doi:10.1053/j.gastro.2011.04.061]).

"After completion of the 12-month assessment, subjects in the sham arm were offered crossover to active (RFA) treatment," wrote the investigators. All 35 of the original 43 sham subjects who were eligible for crossover elected to receive treatment (4 had developed esophageal adenocarcinoma while in the sham arm prior to the 1 year end point, and 4 were lost to follow-up). All treated subjects were then followed for 2 years after receiving RFA therapy.

Overall, 119 subjects underwent ablation (84 at study outset plus 35 crossovers), with 106 completing at least the 2-year follow-up. At 2 years, 101 of 106 (95%) of subjects had complete eradication of dysplasia, and 99 of 106 (93%) had complete eradication of intestinal metaplasia, the authors reported. However, over the mean follow-up period of 3.05 years, 25 subjects required an interim focal treatment of recurrent Barrett’s. Moreover, "in the most stringent analysis, if we include any subject who ever received any RFA and left the trial before the 2 year end point as a failure (n = 13), the response rates were 101/119 (85%)" for complete eradication of dysplasia and 99 of 119 (83%) for complete eradication of intestinal metaplasia, the authors added.

Among the 56 subjects for whom 3-year follow-up data were available, 55 (98%) had complete eradication of dysplasia and 51 (91%) had complete eradication of intestinal metaplasia. The annual rate of any neoplastic progression was 1.37% per patient-year, or 1/73 patient-years.

Four serious adverse events have occurred to date in the 119 subjects (3.4%): one upper gastrointestinal bleed in a patient on dual aspirin and clopidogrel therapy for heart disease; one episode of chest pain occurring 8 days following ablation; and two overnight hospitalizations for nausea and chest pain immediately following the procedure.

"The main adverse side effect was stricture occurrence, which occurred in 7.6% of subjects and was correctable with a mean of 2.8 dilation sessions," the investigators wrote. There were no perforations or procedure-related deaths.

Radiofrequency ablation in this study was accomplished with a device made by BÂRRX Medical, which supported both the 2009 study and the current follow-up. Several investigators also reported financial relationships with BÂRRX Medical, among other pharmaceutical makers. AstraZeneca supplied esomeprazole for the patients through the company’s investigator-sponsored study program.

At 3 years, radiofrequency ablation for dysplastic Barrett’s esophagus resulted in complete eradication of dysplasia in 98% of patients, Dr. Nicholas J. Shaheen and colleagues reported in the August issue of Gastroenterology.

The finding represents the latest results from the Ablation of Intestinal Metaplasia Containing Dysplasia Study (AIM Dysplasia Study). The study’s 12-month results were published by Dr. Shaheen and colleagues in 2009 (N. Engl. J. Med. 2009;360:2277-88).

According to Dr. Shaheen, director of the center for esophageal diseases and swallowing at the University of North Carolina, Chapel Hill, the original study recruited 127 patients aged 18-80 years with nonnodular Barrett’s esophagus less than or equal to 8 cm in length.

Patients were randomized in a 2:1 ratio to either radiofrequency ablation (n = 84) or endoscopic surveillance – simple endoscopy with no treatment, the sham arm (n = 43). In the current follow-up, Dr. Shaheen and his colleagues reported on the durability of the treatment at 2 and 3 years post ablation Gastroenterology 2011 August [doi:10.1053/j.gastro.2011.04.061]).

"After completion of the 12-month assessment, subjects in the sham arm were offered crossover to active (RFA) treatment," wrote the investigators. All 35 of the original 43 sham subjects who were eligible for crossover elected to receive treatment (4 had developed esophageal adenocarcinoma while in the sham arm prior to the 1 year end point, and 4 were lost to follow-up). All treated subjects were then followed for 2 years after receiving RFA therapy.

Overall, 119 subjects underwent ablation (84 at study outset plus 35 crossovers), with 106 completing at least the 2-year follow-up. At 2 years, 101 of 106 (95%) of subjects had complete eradication of dysplasia, and 99 of 106 (93%) had complete eradication of intestinal metaplasia, the authors reported. However, over the mean follow-up period of 3.05 years, 25 subjects required an interim focal treatment of recurrent Barrett’s. Moreover, "in the most stringent analysis, if we include any subject who ever received any RFA and left the trial before the 2 year end point as a failure (n = 13), the response rates were 101/119 (85%)" for complete eradication of dysplasia and 99 of 119 (83%) for complete eradication of intestinal metaplasia, the authors added.

Among the 56 subjects for whom 3-year follow-up data were available, 55 (98%) had complete eradication of dysplasia and 51 (91%) had complete eradication of intestinal metaplasia. The annual rate of any neoplastic progression was 1.37% per patient-year, or 1/73 patient-years.

Four serious adverse events have occurred to date in the 119 subjects (3.4%): one upper gastrointestinal bleed in a patient on dual aspirin and clopidogrel therapy for heart disease; one episode of chest pain occurring 8 days following ablation; and two overnight hospitalizations for nausea and chest pain immediately following the procedure.

"The main adverse side effect was stricture occurrence, which occurred in 7.6% of subjects and was correctable with a mean of 2.8 dilation sessions," the investigators wrote. There were no perforations or procedure-related deaths.

Radiofrequency ablation in this study was accomplished with a device made by BÂRRX Medical, which supported both the 2009 study and the current follow-up. Several investigators also reported financial relationships with BÂRRX Medical, among other pharmaceutical makers. AstraZeneca supplied esomeprazole for the patients through the company’s investigator-sponsored study program.