Denise Napoli

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.

"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).

© nebari/Thinkstock

"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.

Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.

Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).

All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.

At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.

The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."

Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.

Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm² vs. 15 cm²; P less than .01).

Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).

Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.

Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).

This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.

The authors disclosed no conflicts of interest or outside funding. 

Nucleoside analogues are effective at preventing hepatocellular carcinoma in hepatitis B, but all are not equal when it comes to overall mortality and liver transplant, according to two new studies in the July issue of Gastroenterology.

In the first study, Dr. Chun-Ying Wu of the National Yang-Ming University, in Taipei, Taiwan, and his colleagues examined the long-term protective effects of nucleoside analogue therapy among chronic hepatitis B patients (doi.org/10.1053/j.gastro.2014.03.048).

They conducted a retrospective nationwide cohort study using data from Taiwan’s National Health Insurance Research Database, collecting records from 1997 through 2010 on patients with chronic hepatitis B.

In total, Dr. Wu looked at 21,595 patients who had been treated for at least 90 days with nucleoside analogues and the same number of propensity-matched patients who had not; patients with hepatitis C, HIV, or cancer developed before the index date were excluded from the analysis.

Among the treated patients, 19,063 received only one nucleoside analogue, including lamivudine (n = 12,938), entecavir (5,748), and telbivudine (377). The remaining 2,532 patients received more than one.

Over a mean follow-up period of 3.46 years and 5.24 years for the treated and untreated cohorts, respectively, the authors found that patients treated with nucleoside analogues had a significantly lower incidence of hepatocellular carcinoma (HCC) (n = 992, or 4.6%), compared with their untreated counterparts (n = 4,454, or 20.6%).

Patients treated with nucleoside analogues also demonstrated a much-lower 7-year cumulative incidence of HCC, compared with untreated patients (7.32% vs. 22.70%; P less than .001).

That translated to an average annual incidence of HCC of 1.05% and 3.24% for treated and untreated patients, respectively.

Dr. Wu and his colleagues disclosed no personal conflicts of interest; they wrote that their work received support from Taiwan’s National Health Research Institutes, the Taipei Veterans General Hospital and Department of Health, and the National Yang-Ming University.

The second study, led by Dr. Young-Suk Lim of the Asan Medical Center, in Seoul, sought to determine which nucleoside analogue offered better protection against not only HCC, but also liver transplant and mortality: entecavir, or the "less potent" lamivudine.

In that report, the researchers conducted a retrospective analysis of 5,374 consecutive adult patients with chronic hepatitis B, treated with entecavir (n = 2,000) or lamivudine (n = 3,374) at a single center in Seoul between 1999 and 2011 (doi.org/10.1053/j.gastro.2014.02.033).

The researchers found that, when looking at propensity-matched pairs, after 3 years of follow-up the risk of death or transplantation diverged significantly: Compared with the lamivudine cohort, entecavir patients had a hazard ratio for these outcomes of 0.49 (95% confidence interval, 0.37-0.64; P less than .001).

On the other hand, looking at the risk for HCC development, there was no significant difference between groups (HR, 1.01; 95% CI, 0.80-1.27; P = .95).

When an adjusted analysis of matched pairs with cirrhosis at study baseline was undertaken, the results were similar: entecavir was associated with a significantly lower risk of death or transplantation, compared with lamivudine (HR, 0.42; 95% CI, 0.31-0.57; P less than .001), but not HCC (HR, 1.00; 95% CI, 0.78-1.28; P = .999).

An analysis of patients without baseline cirrhosis, however, showed no difference between any of the outcomes: transplant, death, or HCC.

"These results advocate current practice guidelines that recommend the use of two potent antiviral agents (that is, entecavir and tenofovir) as first-line drugs for the treatment of chronic hepatitis B," wrote the authors.

"Further longer-term studies on patients of other races or ethnicity, and studies using other potent antiviral agents such as tenofovir, are warranted."

Dr. Lim disclosed financial relationships with Bayer Healthcare, Bristol-Myers Squibb (maker of entecavir), Gilead Science and Novartis; the investigators stated that their study received funding from the Asan Medical Center and the Korean Association for the Study of Liver.

Nucleoside analogues are effective at preventing hepatocellular carcinoma in hepatitis B, but all are not equal when it comes to overall mortality and liver transplant, according to two new studies in the July issue of Gastroenterology.

In the first study, Dr. Chun-Ying Wu of the National Yang-Ming University, in Taipei, Taiwan, and his colleagues examined the long-term protective effects of nucleoside analogue therapy among chronic hepatitis B patients (doi.org/10.1053/j.gastro.2014.03.048).

They conducted a retrospective nationwide cohort study using data from Taiwan’s National Health Insurance Research Database, collecting records from 1997 through 2010 on patients with chronic hepatitis B.

In total, Dr. Wu looked at 21,595 patients who had been treated for at least 90 days with nucleoside analogues and the same number of propensity-matched patients who had not; patients with hepatitis C, HIV, or cancer developed before the index date were excluded from the analysis.

Among the treated patients, 19,063 received only one nucleoside analogue, including lamivudine (n = 12,938), entecavir (5,748), and telbivudine (377). The remaining 2,532 patients received more than one.

Over a mean follow-up period of 3.46 years and 5.24 years for the treated and untreated cohorts, respectively, the authors found that patients treated with nucleoside analogues had a significantly lower incidence of hepatocellular carcinoma (HCC) (n = 992, or 4.6%), compared with their untreated counterparts (n = 4,454, or 20.6%).

Patients treated with nucleoside analogues also demonstrated a much-lower 7-year cumulative incidence of HCC, compared with untreated patients (7.32% vs. 22.70%; P less than .001).

That translated to an average annual incidence of HCC of 1.05% and 3.24% for treated and untreated patients, respectively.

Dr. Wu and his colleagues disclosed no personal conflicts of interest; they wrote that their work received support from Taiwan’s National Health Research Institutes, the Taipei Veterans General Hospital and Department of Health, and the National Yang-Ming University.

The second study, led by Dr. Young-Suk Lim of the Asan Medical Center, in Seoul, sought to determine which nucleoside analogue offered better protection against not only HCC, but also liver transplant and mortality: entecavir, or the "less potent" lamivudine.

In that report, the researchers conducted a retrospective analysis of 5,374 consecutive adult patients with chronic hepatitis B, treated with entecavir (n = 2,000) or lamivudine (n = 3,374) at a single center in Seoul between 1999 and 2011 (doi.org/10.1053/j.gastro.2014.02.033).

The researchers found that, when looking at propensity-matched pairs, after 3 years of follow-up the risk of death or transplantation diverged significantly: Compared with the lamivudine cohort, entecavir patients had a hazard ratio for these outcomes of 0.49 (95% confidence interval, 0.37-0.64; P less than .001).

On the other hand, looking at the risk for HCC development, there was no significant difference between groups (HR, 1.01; 95% CI, 0.80-1.27; P = .95).

When an adjusted analysis of matched pairs with cirrhosis at study baseline was undertaken, the results were similar: entecavir was associated with a significantly lower risk of death or transplantation, compared with lamivudine (HR, 0.42; 95% CI, 0.31-0.57; P less than .001), but not HCC (HR, 1.00; 95% CI, 0.78-1.28; P = .999).

An analysis of patients without baseline cirrhosis, however, showed no difference between any of the outcomes: transplant, death, or HCC.

"These results advocate current practice guidelines that recommend the use of two potent antiviral agents (that is, entecavir and tenofovir) as first-line drugs for the treatment of chronic hepatitis B," wrote the authors.

"Further longer-term studies on patients of other races or ethnicity, and studies using other potent antiviral agents such as tenofovir, are warranted."

Dr. Lim disclosed financial relationships with Bayer Healthcare, Bristol-Myers Squibb (maker of entecavir), Gilead Science and Novartis; the investigators stated that their study received funding from the Asan Medical Center and the Korean Association for the Study of Liver.

Nucleoside analogues are effective at preventing hepatocellular carcinoma in hepatitis B, but all are not equal when it comes to overall mortality and liver transplant, according to two new studies in the July issue of Gastroenterology.

In the first study, Dr. Chun-Ying Wu of the National Yang-Ming University, in Taipei, Taiwan, and his colleagues examined the long-term protective effects of nucleoside analogue therapy among chronic hepatitis B patients (doi.org/10.1053/j.gastro.2014.03.048).

They conducted a retrospective nationwide cohort study using data from Taiwan’s National Health Insurance Research Database, collecting records from 1997 through 2010 on patients with chronic hepatitis B.

In total, Dr. Wu looked at 21,595 patients who had been treated for at least 90 days with nucleoside analogues and the same number of propensity-matched patients who had not; patients with hepatitis C, HIV, or cancer developed before the index date were excluded from the analysis.

Among the treated patients, 19,063 received only one nucleoside analogue, including lamivudine (n = 12,938), entecavir (5,748), and telbivudine (377). The remaining 2,532 patients received more than one.

Over a mean follow-up period of 3.46 years and 5.24 years for the treated and untreated cohorts, respectively, the authors found that patients treated with nucleoside analogues had a significantly lower incidence of hepatocellular carcinoma (HCC) (n = 992, or 4.6%), compared with their untreated counterparts (n = 4,454, or 20.6%).

Patients treated with nucleoside analogues also demonstrated a much-lower 7-year cumulative incidence of HCC, compared with untreated patients (7.32% vs. 22.70%; P less than .001).

That translated to an average annual incidence of HCC of 1.05% and 3.24% for treated and untreated patients, respectively.

Dr. Wu and his colleagues disclosed no personal conflicts of interest; they wrote that their work received support from Taiwan’s National Health Research Institutes, the Taipei Veterans General Hospital and Department of Health, and the National Yang-Ming University.

The second study, led by Dr. Young-Suk Lim of the Asan Medical Center, in Seoul, sought to determine which nucleoside analogue offered better protection against not only HCC, but also liver transplant and mortality: entecavir, or the "less potent" lamivudine.

In that report, the researchers conducted a retrospective analysis of 5,374 consecutive adult patients with chronic hepatitis B, treated with entecavir (n = 2,000) or lamivudine (n = 3,374) at a single center in Seoul between 1999 and 2011 (doi.org/10.1053/j.gastro.2014.02.033).

The researchers found that, when looking at propensity-matched pairs, after 3 years of follow-up the risk of death or transplantation diverged significantly: Compared with the lamivudine cohort, entecavir patients had a hazard ratio for these outcomes of 0.49 (95% confidence interval, 0.37-0.64; P less than .001).

On the other hand, looking at the risk for HCC development, there was no significant difference between groups (HR, 1.01; 95% CI, 0.80-1.27; P = .95).

When an adjusted analysis of matched pairs with cirrhosis at study baseline was undertaken, the results were similar: entecavir was associated with a significantly lower risk of death or transplantation, compared with lamivudine (HR, 0.42; 95% CI, 0.31-0.57; P less than .001), but not HCC (HR, 1.00; 95% CI, 0.78-1.28; P = .999).

An analysis of patients without baseline cirrhosis, however, showed no difference between any of the outcomes: transplant, death, or HCC.

"These results advocate current practice guidelines that recommend the use of two potent antiviral agents (that is, entecavir and tenofovir) as first-line drugs for the treatment of chronic hepatitis B," wrote the authors.

"Further longer-term studies on patients of other races or ethnicity, and studies using other potent antiviral agents such as tenofovir, are warranted."

Dr. Lim disclosed financial relationships with Bayer Healthcare, Bristol-Myers Squibb (maker of entecavir), Gilead Science and Novartis; the investigators stated that their study received funding from the Asan Medical Center and the Korean Association for the Study of Liver.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Annual surveillance of serrated polyposis syndrome patients detected a relatively high rate of advanced adenomas and large serrated polyps, reported Dr. Yark Hazewinkel and colleagues in the July issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.03.015).

"Due to a lack of prospective data, the optimal treatment approach with regard to surveillance intervals and polypectomy protocol [for this population] is still largely unknown," they wrote.

However, "considering the high polyp recurrence rate observed in our series, close endoscopic surveillance seems justified."

Dr. Hazewinkel of the Academic Medical Center in Amsterdam and colleagues looked at consecutive patients with serrated polyposis syndrome (SPS) who presented to their facility between January 2007 and December 2012.

Using the World Health Organization criteria for SPS, the investigators found that all patients had at least five histologically diagnosed serrated polyps proximal to the sigmoid colon, of which 2 measured 10 mm in diameter or more, and/or at least 20 serrated polyps spread throughout the colon.

In total, 50 patients were selected to undergo an index clearing colonoscopy with the goal of removing all polyps measuring 3 mm or more. This was achieved in 41 patients, who had a mean age of 57 years; 60% were male.

The remaining nine patients were referred for prophylactic surgery because of an "endoscopically untreatable number of polyps."

Ultimately, 37 patients underwent at least 1 surveillance colonoscopy, and a total of 119 colonoscopies were done over a median of 3.1 years of follow-up.

Looking at the primary outcome – detected cases of colorectal cancer – the authors tallied zero cases during surveillance colonoscopy in these patients.

Advanced adenomas were detected in 3 of the 37 patients (8%), with a median interval between last clearing colonoscopy and discovery of 13 months (range, 12-25 months), for a cumulative risk of 9% for detecting at least one advanced adenoma after three surveillance colonoscopies.

Meanwhile, large serrated polyps (defined as hyperplastic polyps or sessile serrated adenomas/polyps of 10 mm or greater) were detected in 11 of 37 patients (30%), with a median interval after clearing colonoscopy to detection of 21 months, for a cumulative risk of at least one large serrated polyp after three surveillance colonoscopies of 34%.

The authors said this study had several limitations, namely the small sample size and relatively short follow-up period.

Nevertheless, "the present study is the largest prospective study available, and the current findings add substantially to our understanding of the longitudinal [colorectal cancer] risk in SPS patients under strict endoscopic surveillance," they wrote.

In addition, of the 993 lesions removed between 3 and 5 mm in their cohort at clearing colonoscopy, none contained high-grade dysplasia or invasive cancer.

"Considering that patients with SPS have many diminutive lesions, leaving these lesions in situ until they reach a certain size (i.e., 6 mm) would substantially reduce the workload of the endoscopist and decrease the pathology costs, but the safety of this approach should first be prospectively assessed," the researchers wrote.

The authors disclosed no conflicts of interest relating to this study, which was supported by the Dutch Cancer Society.

Annual surveillance of serrated polyposis syndrome patients detected a relatively high rate of advanced adenomas and large serrated polyps, reported Dr. Yark Hazewinkel and colleagues in the July issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.03.015).

"Due to a lack of prospective data, the optimal treatment approach with regard to surveillance intervals and polypectomy protocol [for this population] is still largely unknown," they wrote.

However, "considering the high polyp recurrence rate observed in our series, close endoscopic surveillance seems justified."

Dr. Hazewinkel of the Academic Medical Center in Amsterdam and colleagues looked at consecutive patients with serrated polyposis syndrome (SPS) who presented to their facility between January 2007 and December 2012.

Using the World Health Organization criteria for SPS, the investigators found that all patients had at least five histologically diagnosed serrated polyps proximal to the sigmoid colon, of which 2 measured 10 mm in diameter or more, and/or at least 20 serrated polyps spread throughout the colon.

In total, 50 patients were selected to undergo an index clearing colonoscopy with the goal of removing all polyps measuring 3 mm or more. This was achieved in 41 patients, who had a mean age of 57 years; 60% were male.

The remaining nine patients were referred for prophylactic surgery because of an "endoscopically untreatable number of polyps."

Ultimately, 37 patients underwent at least 1 surveillance colonoscopy, and a total of 119 colonoscopies were done over a median of 3.1 years of follow-up.

Looking at the primary outcome – detected cases of colorectal cancer – the authors tallied zero cases during surveillance colonoscopy in these patients.

Advanced adenomas were detected in 3 of the 37 patients (8%), with a median interval between last clearing colonoscopy and discovery of 13 months (range, 12-25 months), for a cumulative risk of 9% for detecting at least one advanced adenoma after three surveillance colonoscopies.

Meanwhile, large serrated polyps (defined as hyperplastic polyps or sessile serrated adenomas/polyps of 10 mm or greater) were detected in 11 of 37 patients (30%), with a median interval after clearing colonoscopy to detection of 21 months, for a cumulative risk of at least one large serrated polyp after three surveillance colonoscopies of 34%.

The authors said this study had several limitations, namely the small sample size and relatively short follow-up period.

Nevertheless, "the present study is the largest prospective study available, and the current findings add substantially to our understanding of the longitudinal [colorectal cancer] risk in SPS patients under strict endoscopic surveillance," they wrote.

In addition, of the 993 lesions removed between 3 and 5 mm in their cohort at clearing colonoscopy, none contained high-grade dysplasia or invasive cancer.

"Considering that patients with SPS have many diminutive lesions, leaving these lesions in situ until they reach a certain size (i.e., 6 mm) would substantially reduce the workload of the endoscopist and decrease the pathology costs, but the safety of this approach should first be prospectively assessed," the researchers wrote.

The authors disclosed no conflicts of interest relating to this study, which was supported by the Dutch Cancer Society.

Annual surveillance of serrated polyposis syndrome patients detected a relatively high rate of advanced adenomas and large serrated polyps, reported Dr. Yark Hazewinkel and colleagues in the July issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.03.015).

"Due to a lack of prospective data, the optimal treatment approach with regard to surveillance intervals and polypectomy protocol [for this population] is still largely unknown," they wrote.

However, "considering the high polyp recurrence rate observed in our series, close endoscopic surveillance seems justified."

Dr. Hazewinkel of the Academic Medical Center in Amsterdam and colleagues looked at consecutive patients with serrated polyposis syndrome (SPS) who presented to their facility between January 2007 and December 2012.

Using the World Health Organization criteria for SPS, the investigators found that all patients had at least five histologically diagnosed serrated polyps proximal to the sigmoid colon, of which 2 measured 10 mm in diameter or more, and/or at least 20 serrated polyps spread throughout the colon.

In total, 50 patients were selected to undergo an index clearing colonoscopy with the goal of removing all polyps measuring 3 mm or more. This was achieved in 41 patients, who had a mean age of 57 years; 60% were male.

The remaining nine patients were referred for prophylactic surgery because of an "endoscopically untreatable number of polyps."

Ultimately, 37 patients underwent at least 1 surveillance colonoscopy, and a total of 119 colonoscopies were done over a median of 3.1 years of follow-up.

Looking at the primary outcome – detected cases of colorectal cancer – the authors tallied zero cases during surveillance colonoscopy in these patients.

Advanced adenomas were detected in 3 of the 37 patients (8%), with a median interval between last clearing colonoscopy and discovery of 13 months (range, 12-25 months), for a cumulative risk of 9% for detecting at least one advanced adenoma after three surveillance colonoscopies.

Meanwhile, large serrated polyps (defined as hyperplastic polyps or sessile serrated adenomas/polyps of 10 mm or greater) were detected in 11 of 37 patients (30%), with a median interval after clearing colonoscopy to detection of 21 months, for a cumulative risk of at least one large serrated polyp after three surveillance colonoscopies of 34%.

The authors said this study had several limitations, namely the small sample size and relatively short follow-up period.

Nevertheless, "the present study is the largest prospective study available, and the current findings add substantially to our understanding of the longitudinal [colorectal cancer] risk in SPS patients under strict endoscopic surveillance," they wrote.

In addition, of the 993 lesions removed between 3 and 5 mm in their cohort at clearing colonoscopy, none contained high-grade dysplasia or invasive cancer.

"Considering that patients with SPS have many diminutive lesions, leaving these lesions in situ until they reach a certain size (i.e., 6 mm) would substantially reduce the workload of the endoscopist and decrease the pathology costs, but the safety of this approach should first be prospectively assessed," the researchers wrote.

The authors disclosed no conflicts of interest relating to this study, which was supported by the Dutch Cancer Society.

NEW YORK – A forthcoming rating system for mental health smartphone applications acknowledges that – for better or worse – these tools are in patients’ hands, Dr. Michael Van Ameringen said in a presentation at the annual meeting of the American Psychiatric Association.

"Like any medical professional, it is our role to keep ourselves updated with our patients’ concerns," Dr. Van Ameringen noted in a follow-up interview. "Many patients are using these apps to enhance the treatment they are receiving from us, or it is their primary source of treatment."

According to Dr. Van Ameringen, professor in the department of psychiatry and behavioral sciences at McMaster University, Hamilton, Ont., the initiative for a rating system comes from the board of directors of the Anxiety and Depression Association of America (ADAA), of which Dr. Van Ameringen is a member.

"Our goal was to make it easier for professionals and consumers to get unbiased professional ratings of currently available apps," Dr. Van Ameringen said. "We plan to rate each one, though we are not going to rank them or endorse one app over the other."

The list of apps was developed by a search of the iTunes store, Google Play store and BlackBerry World; the final review will be available on the ADAA website.

Dr. Van Ameringen pointed to two apps that will be featured on the ADAA review that he said have gained distinct popularity.

The first, Prolonged Exposure (PE) Coach, is intended to be used as a "treatment companion" during prolonged exposure therapy for posttraumatic stress disorder, according to the U.S. Department of Veterans Affairs website.

It was created by the U.S. Department of Defense’s National Center for Telehealth and Technology and Center for Deployment Psychology and the VA’s National Center for PTSD.

Another, MindShift, is geared toward "teens and young adults coping with anxiety," according to the website for AnxietyBC, a nonprofit that developed the app in concert with the BC Mental Health & Addiction Services, an agency of the Provincial Health Services Authority.

"We know that many of these apps are very popular and are downloaded a significant number of times," Dr. Van Ameringen said. "We don’t really know how many people are using them on a day-to-day basis."

Despite their popularity, the proliferation of mental health apps poses several issues for providers seeking to recommend their use.

"Confidentiality is the biggest challenge with these apps," Dr. Van Ameringen said. "Consumers may also believe that the app alone is a good substitute for professional assessment and treatment."

Perhaps the most worrisome problem is the fact that most apps have not been evaluated with customary scientific rigor, said Dr. Ameringen.

Going forward, said Dr. Van Ameringen, more clinical trials must be conducted on these apps’ efficacy, and head-to-head trials should compare them to current treatments.

One thing is sure: The mental health app landscape continues to expand, and patients have taken notice. That means providers must take notice, too.

"We need to understand where these apps fit into our current treatment model and how they can be used most effectively in our patients," he said.

Dr. Van Ameringen disclosed financial relationships with several pharmaceutical companies, including Valiant, Eli Lilly, Pfizer, and GlaxoSmithKline.

NEW YORK – A forthcoming rating system for mental health smartphone applications acknowledges that – for better or worse – these tools are in patients’ hands, Dr. Michael Van Ameringen said in a presentation at the annual meeting of the American Psychiatric Association.

"Like any medical professional, it is our role to keep ourselves updated with our patients’ concerns," Dr. Van Ameringen noted in a follow-up interview. "Many patients are using these apps to enhance the treatment they are receiving from us, or it is their primary source of treatment."

According to Dr. Van Ameringen, professor in the department of psychiatry and behavioral sciences at McMaster University, Hamilton, Ont., the initiative for a rating system comes from the board of directors of the Anxiety and Depression Association of America (ADAA), of which Dr. Van Ameringen is a member.

"Our goal was to make it easier for professionals and consumers to get unbiased professional ratings of currently available apps," Dr. Van Ameringen said. "We plan to rate each one, though we are not going to rank them or endorse one app over the other."

The list of apps was developed by a search of the iTunes store, Google Play store and BlackBerry World; the final review will be available on the ADAA website.

Dr. Van Ameringen pointed to two apps that will be featured on the ADAA review that he said have gained distinct popularity.

The first, Prolonged Exposure (PE) Coach, is intended to be used as a "treatment companion" during prolonged exposure therapy for posttraumatic stress disorder, according to the U.S. Department of Veterans Affairs website.

It was created by the U.S. Department of Defense’s National Center for Telehealth and Technology and Center for Deployment Psychology and the VA’s National Center for PTSD.

Another, MindShift, is geared toward "teens and young adults coping with anxiety," according to the website for AnxietyBC, a nonprofit that developed the app in concert with the BC Mental Health & Addiction Services, an agency of the Provincial Health Services Authority.

"We know that many of these apps are very popular and are downloaded a significant number of times," Dr. Van Ameringen said. "We don’t really know how many people are using them on a day-to-day basis."

Despite their popularity, the proliferation of mental health apps poses several issues for providers seeking to recommend their use.

"Confidentiality is the biggest challenge with these apps," Dr. Van Ameringen said. "Consumers may also believe that the app alone is a good substitute for professional assessment and treatment."

Perhaps the most worrisome problem is the fact that most apps have not been evaluated with customary scientific rigor, said Dr. Ameringen.

Going forward, said Dr. Van Ameringen, more clinical trials must be conducted on these apps’ efficacy, and head-to-head trials should compare them to current treatments.

One thing is sure: The mental health app landscape continues to expand, and patients have taken notice. That means providers must take notice, too.

"We need to understand where these apps fit into our current treatment model and how they can be used most effectively in our patients," he said.

Dr. Van Ameringen disclosed financial relationships with several pharmaceutical companies, including Valiant, Eli Lilly, Pfizer, and GlaxoSmithKline.

NEW YORK – A forthcoming rating system for mental health smartphone applications acknowledges that – for better or worse – these tools are in patients’ hands, Dr. Michael Van Ameringen said in a presentation at the annual meeting of the American Psychiatric Association.

"Like any medical professional, it is our role to keep ourselves updated with our patients’ concerns," Dr. Van Ameringen noted in a follow-up interview. "Many patients are using these apps to enhance the treatment they are receiving from us, or it is their primary source of treatment."

According to Dr. Van Ameringen, professor in the department of psychiatry and behavioral sciences at McMaster University, Hamilton, Ont., the initiative for a rating system comes from the board of directors of the Anxiety and Depression Association of America (ADAA), of which Dr. Van Ameringen is a member.

"Our goal was to make it easier for professionals and consumers to get unbiased professional ratings of currently available apps," Dr. Van Ameringen said. "We plan to rate each one, though we are not going to rank them or endorse one app over the other."

The list of apps was developed by a search of the iTunes store, Google Play store and BlackBerry World; the final review will be available on the ADAA website.

Dr. Van Ameringen pointed to two apps that will be featured on the ADAA review that he said have gained distinct popularity.

The first, Prolonged Exposure (PE) Coach, is intended to be used as a "treatment companion" during prolonged exposure therapy for posttraumatic stress disorder, according to the U.S. Department of Veterans Affairs website.

It was created by the U.S. Department of Defense’s National Center for Telehealth and Technology and Center for Deployment Psychology and the VA’s National Center for PTSD.

Another, MindShift, is geared toward "teens and young adults coping with anxiety," according to the website for AnxietyBC, a nonprofit that developed the app in concert with the BC Mental Health & Addiction Services, an agency of the Provincial Health Services Authority.

"We know that many of these apps are very popular and are downloaded a significant number of times," Dr. Van Ameringen said. "We don’t really know how many people are using them on a day-to-day basis."

Despite their popularity, the proliferation of mental health apps poses several issues for providers seeking to recommend their use.

"Confidentiality is the biggest challenge with these apps," Dr. Van Ameringen said. "Consumers may also believe that the app alone is a good substitute for professional assessment and treatment."

Perhaps the most worrisome problem is the fact that most apps have not been evaluated with customary scientific rigor, said Dr. Ameringen.

Going forward, said Dr. Van Ameringen, more clinical trials must be conducted on these apps’ efficacy, and head-to-head trials should compare them to current treatments.

One thing is sure: The mental health app landscape continues to expand, and patients have taken notice. That means providers must take notice, too.

"We need to understand where these apps fit into our current treatment model and how they can be used most effectively in our patients," he said.

Dr. Van Ameringen disclosed financial relationships with several pharmaceutical companies, including Valiant, Eli Lilly, Pfizer, and GlaxoSmithKline.

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.