Denise Napoli

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.