IBD & Intestinal Disorders

Norovirus is now the leading cause of acute gastroenteritis requiring medical care among U.S. children younger than 5 years of age, according to a report published online March 20 in the New England Journal of Medicine.

Now that rotavirus vaccines have dramatically reduced the number of acute gastroenteritis cases attributable to that organism, norovirus infections have taken over the lead in causing the disorder in the young U.S. pediatric population. Norovirus is responsible for an estimated 1 million health care visits each year for this age group, at an estimated cost approaching $300 million, said Daniel C. Payne, Ph.D., of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, and his associates.

"According to our estimation, by their fifth birthday, 1 in 278 U.S. children are hospitalized for norovirus infection, 1 in 14 are seen in the emergency department, and 1 in 6 are seen by outpatient care providers," the investigators noted.

They studied the epidemiology of the infection because now that candidate norovirus vaccines are in development, "there is a need to directly measure the pediatric health care burden of norovirus-associated gastroenteritis."

Dr. Payne and his colleagues analyzed data from the New Vaccine Surveillance Network, which collects information on the medical care of children residing near Rochester, N.Y.; Nashville, Tenn.; and Cincinnati – a catchment population exceeding 141,000 children under age 5.

The researchers prospectively assessed cases of acute gastroenteritis treated at hospitals, emergency departments, and outpatient clinics during two successive 12-month surveillance periods between October 2008 and September 2010. There were 1,077 cases the first year and 820 the second year; the data from these were compared with data from 806 age-matched children attending well-child visits, who served as a control group.

The disease burden of norovirus infection was "consistently high" during both years, accounting for 20%-22% of cases of acute gastroenteritis. Norovirus was detected in 4% of healthy controls in 2009. The overall rate of medical attention for the infection was highest – 47% – among children aged 6-18 months, Dr. Payne and his associates reported (N. Engl. J. Med. 2013;368:1121-30).

This study was supported by the CDC. Dr. Payne reported that he did not have any conflicts of interest relevant to this study. His coauthors reported ties to GlaxoSmithKline, Merck, and Luminex Molecular Diagnostics.

Norovirus is now the leading cause of acute gastroenteritis requiring medical care among U.S. children younger than 5 years of age, according to a report published online March 20 in the New England Journal of Medicine.

Now that rotavirus vaccines have dramatically reduced the number of acute gastroenteritis cases attributable to that organism, norovirus infections have taken over the lead in causing the disorder in the young U.S. pediatric population. Norovirus is responsible for an estimated 1 million health care visits each year for this age group, at an estimated cost approaching $300 million, said Daniel C. Payne, Ph.D., of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, and his associates.

"According to our estimation, by their fifth birthday, 1 in 278 U.S. children are hospitalized for norovirus infection, 1 in 14 are seen in the emergency department, and 1 in 6 are seen by outpatient care providers," the investigators noted.

They studied the epidemiology of the infection because now that candidate norovirus vaccines are in development, "there is a need to directly measure the pediatric health care burden of norovirus-associated gastroenteritis."

Dr. Payne and his colleagues analyzed data from the New Vaccine Surveillance Network, which collects information on the medical care of children residing near Rochester, N.Y.; Nashville, Tenn.; and Cincinnati – a catchment population exceeding 141,000 children under age 5.

The researchers prospectively assessed cases of acute gastroenteritis treated at hospitals, emergency departments, and outpatient clinics during two successive 12-month surveillance periods between October 2008 and September 2010. There were 1,077 cases the first year and 820 the second year; the data from these were compared with data from 806 age-matched children attending well-child visits, who served as a control group.

The disease burden of norovirus infection was "consistently high" during both years, accounting for 20%-22% of cases of acute gastroenteritis. Norovirus was detected in 4% of healthy controls in 2009. The overall rate of medical attention for the infection was highest – 47% – among children aged 6-18 months, Dr. Payne and his associates reported (N. Engl. J. Med. 2013;368:1121-30).

This study was supported by the CDC. Dr. Payne reported that he did not have any conflicts of interest relevant to this study. His coauthors reported ties to GlaxoSmithKline, Merck, and Luminex Molecular Diagnostics.

Norovirus is now the leading cause of acute gastroenteritis requiring medical care among U.S. children younger than 5 years of age, according to a report published online March 20 in the New England Journal of Medicine.

Now that rotavirus vaccines have dramatically reduced the number of acute gastroenteritis cases attributable to that organism, norovirus infections have taken over the lead in causing the disorder in the young U.S. pediatric population. Norovirus is responsible for an estimated 1 million health care visits each year for this age group, at an estimated cost approaching $300 million, said Daniel C. Payne, Ph.D., of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, and his associates.

"According to our estimation, by their fifth birthday, 1 in 278 U.S. children are hospitalized for norovirus infection, 1 in 14 are seen in the emergency department, and 1 in 6 are seen by outpatient care providers," the investigators noted.

They studied the epidemiology of the infection because now that candidate norovirus vaccines are in development, "there is a need to directly measure the pediatric health care burden of norovirus-associated gastroenteritis."

Dr. Payne and his colleagues analyzed data from the New Vaccine Surveillance Network, which collects information on the medical care of children residing near Rochester, N.Y.; Nashville, Tenn.; and Cincinnati – a catchment population exceeding 141,000 children under age 5.

The researchers prospectively assessed cases of acute gastroenteritis treated at hospitals, emergency departments, and outpatient clinics during two successive 12-month surveillance periods between October 2008 and September 2010. There were 1,077 cases the first year and 820 the second year; the data from these were compared with data from 806 age-matched children attending well-child visits, who served as a control group.

The disease burden of norovirus infection was "consistently high" during both years, accounting for 20%-22% of cases of acute gastroenteritis. Norovirus was detected in 4% of healthy controls in 2009. The overall rate of medical attention for the infection was highest – 47% – among children aged 6-18 months, Dr. Payne and his associates reported (N. Engl. J. Med. 2013;368:1121-30).

This study was supported by the CDC. Dr. Payne reported that he did not have any conflicts of interest relevant to this study. His coauthors reported ties to GlaxoSmithKline, Merck, and Luminex Molecular Diagnostics.

Glycerol phenylbutyrate, a nitrogen-binding agent, has been approved for the chronic treatment of adults and children aged 2 years and older with urea cycle disorders, who cannot be managed with a protein-restricted diet or amino acid supplements alone, the Food and Drug Administration announced on Feb. 1.

The product, in a liquid formulation, helps eliminate excess ammonia that results from the accumulation of nitrogen in people with urea cycle disorders, which are inherited metabolic disorders. The drug is taken three times a day with a protein-restricted diet, according to the FDA statement announcing the approval. In some cases, it is used with dietary supplements, such as amino acids or arginine.

It will be marketed under the trade name Ravicti by Hyperion Therapeutics.

Approval was based on a study of 44 adults with urea cycle disorders, which found that glycerol phenylbutyrate was as effective as sodium phenylbutyrate (Buphenyl), in controlling ammonia levels, according to the FDA. In the study, patients were randomized to treatment with sodium phenylbutyrate, an approved treatment for urea cycle disorders, or glycerol phenylbutyrate for 2 weeks, then were switched to the other treatment for 2 weeks. Another three studies in children and adults "provided evidence supporting the long-term safety and effectiveness of Ravicti in patients 2 years and older," the FDA said.

Diarrhea, flatulence, and headache were the most common side effects associated with treatment, according to the FDA.

The manufacturer expects to launch the product by the end of April 2013 and will distribute it through two specialty pharmacies, according to a Hyperion statement.

e.mechcatie@elsevier.com

Glycerol phenylbutyrate, a nitrogen-binding agent, has been approved for the chronic treatment of adults and children aged 2 years and older with urea cycle disorders, who cannot be managed with a protein-restricted diet or amino acid supplements alone, the Food and Drug Administration announced on Feb. 1.

The product, in a liquid formulation, helps eliminate excess ammonia that results from the accumulation of nitrogen in people with urea cycle disorders, which are inherited metabolic disorders. The drug is taken three times a day with a protein-restricted diet, according to the FDA statement announcing the approval. In some cases, it is used with dietary supplements, such as amino acids or arginine.

It will be marketed under the trade name Ravicti by Hyperion Therapeutics.

Approval was based on a study of 44 adults with urea cycle disorders, which found that glycerol phenylbutyrate was as effective as sodium phenylbutyrate (Buphenyl), in controlling ammonia levels, according to the FDA. In the study, patients were randomized to treatment with sodium phenylbutyrate, an approved treatment for urea cycle disorders, or glycerol phenylbutyrate for 2 weeks, then were switched to the other treatment for 2 weeks. Another three studies in children and adults "provided evidence supporting the long-term safety and effectiveness of Ravicti in patients 2 years and older," the FDA said.

Diarrhea, flatulence, and headache were the most common side effects associated with treatment, according to the FDA.

The manufacturer expects to launch the product by the end of April 2013 and will distribute it through two specialty pharmacies, according to a Hyperion statement.

e.mechcatie@elsevier.com

Glycerol phenylbutyrate, a nitrogen-binding agent, has been approved for the chronic treatment of adults and children aged 2 years and older with urea cycle disorders, who cannot be managed with a protein-restricted diet or amino acid supplements alone, the Food and Drug Administration announced on Feb. 1.

The product, in a liquid formulation, helps eliminate excess ammonia that results from the accumulation of nitrogen in people with urea cycle disorders, which are inherited metabolic disorders. The drug is taken three times a day with a protein-restricted diet, according to the FDA statement announcing the approval. In some cases, it is used with dietary supplements, such as amino acids or arginine.

It will be marketed under the trade name Ravicti by Hyperion Therapeutics.

Approval was based on a study of 44 adults with urea cycle disorders, which found that glycerol phenylbutyrate was as effective as sodium phenylbutyrate (Buphenyl), in controlling ammonia levels, according to the FDA. In the study, patients were randomized to treatment with sodium phenylbutyrate, an approved treatment for urea cycle disorders, or glycerol phenylbutyrate for 2 weeks, then were switched to the other treatment for 2 weeks. Another three studies in children and adults "provided evidence supporting the long-term safety and effectiveness of Ravicti in patients 2 years and older," the FDA said.

Diarrhea, flatulence, and headache were the most common side effects associated with treatment, according to the FDA.

The manufacturer expects to launch the product by the end of April 2013 and will distribute it through two specialty pharmacies, according to a Hyperion statement.

e.mechcatie@elsevier.com

A new strain of norovirus, identified last March in Australia, has swept through the United States, causing more than half of the 2012 outbreaks.

GII.4 Sydney is implicated in 53% of the outbreaks that occurred from September to December, Leslie Barclay and her colleagues reported in the Jan. 24 issue of the Morbidity and Mortality Weekly Report (2013;62:55).

The other outbreaks were caused by 10 different GI and GII genotypes, including GII.4 New Orleans, said Ms. Barclay of the National Calicivirus Laboratory at the Centers for Disease Control and Prevention, and her coauthors. However, she noted, the GII.4 Sydney virus appears to have replaced the New Orleans strain as the predominant pathogen.

GII.4 Sydney was implicated in 19% of the September norovirus outbreaks; 46% of the October outbreaks; and 58% of outbreaks in both November and December, Ms. Barclay and her coinvestigators said.

The report noted that 51% of the outbreaks were direct, person-to-person transmission; 20% were foodborne; and 1% waterborne. For the other outbreaks, the mode of transmission remains unknown.

The sudden appearance of a new norovirus strain isn’t unusual or unexpected, Dr. Aron J. Hall said in an interview.

"This group of viruses is constantly evolving. New strains develop all the time," said Dr. Hall, an epidemiologist with CDC’s Division of Viral Diseases. "This is following the same pattern we’ve seen for the past 10 years, with a new strain evolving every 2-3 years."

Since the norovirus season doesn’t normally peak until January, it’s too soon to say whether GII.4 Sydney is more virulent, either in the number or severity of cases it causes.

"Every time a new strain emerges, there’s a potential for increased disease activity, numbers of outbreaks, and severity. But sometimes they simply replace the predominant strain with no increases. We have to wait until we’ve tallied all the numbers before we can get an assessment of this season’s magnitude and impact," he said.

GII.4 Sydney was first identified in Australia, and rapidly moved to Japan, the Netherlands, and the United Kingdom, according to a Jan. 4 report (Eurosurv. 2013;18:1)

In early December and late November, the ProMed disease reporting system reported a 64% increase in confirmed norovirus lab reports in England and Wales, and increased deaths in elderly Japanese patients. Molecular assays pinpointed the cause as the new variant of norovirus, the Eurosurveillance researchers noted.

The virus is highly transmissible; exposure to as few as 18 viral particles can cause illness, according to a presentation by Jan Vinjé, Ph.D., head of the National Calicivirus Laboratory. And since about 30% of cases are asymptomatic, the transmission rate can be extremely high.

"These are the two characteristics that explain why norovirus is such a serious public health challenge," Dr. Hall said. "It takes a very tiny amount of exposure to make someone sick, and someone who is sick is shedding billions of viral particles. They can shed virus without any symptoms, so they don’t know they have it and there’s no way to advise them about how to avoid spreading it."

The illness is characterized by vomiting and/or diarrhea with abdominal cramps and low-grade fever. Most patients recover within 12-72 hours, but about 10% need hospitalization and fluid therapy. Severe illness and/or death are most common among the elderly and people with chronic illnesses.

The United States sees about 21 million cases annually; 800 will result in death. A norovirus outbreak can overwhelm local medical resources; the virus causes nearly 2 million outpatient visits and 400,000 emergency department visits each year. The combined annual cost reaches $2 billion, according to the CDC.

As federal employees, Dr. Hall and Ms. Barclay have no financial disclosures.

A new strain of norovirus, identified last March in Australia, has swept through the United States, causing more than half of the 2012 outbreaks.

GII.4 Sydney is implicated in 53% of the outbreaks that occurred from September to December, Leslie Barclay and her colleagues reported in the Jan. 24 issue of the Morbidity and Mortality Weekly Report (2013;62:55).

The other outbreaks were caused by 10 different GI and GII genotypes, including GII.4 New Orleans, said Ms. Barclay of the National Calicivirus Laboratory at the Centers for Disease Control and Prevention, and her coauthors. However, she noted, the GII.4 Sydney virus appears to have replaced the New Orleans strain as the predominant pathogen.

GII.4 Sydney was implicated in 19% of the September norovirus outbreaks; 46% of the October outbreaks; and 58% of outbreaks in both November and December, Ms. Barclay and her coinvestigators said.

The report noted that 51% of the outbreaks were direct, person-to-person transmission; 20% were foodborne; and 1% waterborne. For the other outbreaks, the mode of transmission remains unknown.

The sudden appearance of a new norovirus strain isn’t unusual or unexpected, Dr. Aron J. Hall said in an interview.

"This group of viruses is constantly evolving. New strains develop all the time," said Dr. Hall, an epidemiologist with CDC’s Division of Viral Diseases. "This is following the same pattern we’ve seen for the past 10 years, with a new strain evolving every 2-3 years."

Since the norovirus season doesn’t normally peak until January, it’s too soon to say whether GII.4 Sydney is more virulent, either in the number or severity of cases it causes.

"Every time a new strain emerges, there’s a potential for increased disease activity, numbers of outbreaks, and severity. But sometimes they simply replace the predominant strain with no increases. We have to wait until we’ve tallied all the numbers before we can get an assessment of this season’s magnitude and impact," he said.

GII.4 Sydney was first identified in Australia, and rapidly moved to Japan, the Netherlands, and the United Kingdom, according to a Jan. 4 report (Eurosurv. 2013;18:1)

In early December and late November, the ProMed disease reporting system reported a 64% increase in confirmed norovirus lab reports in England and Wales, and increased deaths in elderly Japanese patients. Molecular assays pinpointed the cause as the new variant of norovirus, the Eurosurveillance researchers noted.

The virus is highly transmissible; exposure to as few as 18 viral particles can cause illness, according to a presentation by Jan Vinjé, Ph.D., head of the National Calicivirus Laboratory. And since about 30% of cases are asymptomatic, the transmission rate can be extremely high.

"These are the two characteristics that explain why norovirus is such a serious public health challenge," Dr. Hall said. "It takes a very tiny amount of exposure to make someone sick, and someone who is sick is shedding billions of viral particles. They can shed virus without any symptoms, so they don’t know they have it and there’s no way to advise them about how to avoid spreading it."

The illness is characterized by vomiting and/or diarrhea with abdominal cramps and low-grade fever. Most patients recover within 12-72 hours, but about 10% need hospitalization and fluid therapy. Severe illness and/or death are most common among the elderly and people with chronic illnesses.

The United States sees about 21 million cases annually; 800 will result in death. A norovirus outbreak can overwhelm local medical resources; the virus causes nearly 2 million outpatient visits and 400,000 emergency department visits each year. The combined annual cost reaches $2 billion, according to the CDC.

As federal employees, Dr. Hall and Ms. Barclay have no financial disclosures.

A new strain of norovirus, identified last March in Australia, has swept through the United States, causing more than half of the 2012 outbreaks.

GII.4 Sydney is implicated in 53% of the outbreaks that occurred from September to December, Leslie Barclay and her colleagues reported in the Jan. 24 issue of the Morbidity and Mortality Weekly Report (2013;62:55).

The other outbreaks were caused by 10 different GI and GII genotypes, including GII.4 New Orleans, said Ms. Barclay of the National Calicivirus Laboratory at the Centers for Disease Control and Prevention, and her coauthors. However, she noted, the GII.4 Sydney virus appears to have replaced the New Orleans strain as the predominant pathogen.

GII.4 Sydney was implicated in 19% of the September norovirus outbreaks; 46% of the October outbreaks; and 58% of outbreaks in both November and December, Ms. Barclay and her coinvestigators said.

The report noted that 51% of the outbreaks were direct, person-to-person transmission; 20% were foodborne; and 1% waterborne. For the other outbreaks, the mode of transmission remains unknown.

The sudden appearance of a new norovirus strain isn’t unusual or unexpected, Dr. Aron J. Hall said in an interview.

"This group of viruses is constantly evolving. New strains develop all the time," said Dr. Hall, an epidemiologist with CDC’s Division of Viral Diseases. "This is following the same pattern we’ve seen for the past 10 years, with a new strain evolving every 2-3 years."

Since the norovirus season doesn’t normally peak until January, it’s too soon to say whether GII.4 Sydney is more virulent, either in the number or severity of cases it causes.

"Every time a new strain emerges, there’s a potential for increased disease activity, numbers of outbreaks, and severity. But sometimes they simply replace the predominant strain with no increases. We have to wait until we’ve tallied all the numbers before we can get an assessment of this season’s magnitude and impact," he said.

GII.4 Sydney was first identified in Australia, and rapidly moved to Japan, the Netherlands, and the United Kingdom, according to a Jan. 4 report (Eurosurv. 2013;18:1)

In early December and late November, the ProMed disease reporting system reported a 64% increase in confirmed norovirus lab reports in England and Wales, and increased deaths in elderly Japanese patients. Molecular assays pinpointed the cause as the new variant of norovirus, the Eurosurveillance researchers noted.

The virus is highly transmissible; exposure to as few as 18 viral particles can cause illness, according to a presentation by Jan Vinjé, Ph.D., head of the National Calicivirus Laboratory. And since about 30% of cases are asymptomatic, the transmission rate can be extremely high.

"These are the two characteristics that explain why norovirus is such a serious public health challenge," Dr. Hall said. "It takes a very tiny amount of exposure to make someone sick, and someone who is sick is shedding billions of viral particles. They can shed virus without any symptoms, so they don’t know they have it and there’s no way to advise them about how to avoid spreading it."

The illness is characterized by vomiting and/or diarrhea with abdominal cramps and low-grade fever. Most patients recover within 12-72 hours, but about 10% need hospitalization and fluid therapy. Severe illness and/or death are most common among the elderly and people with chronic illnesses.

The United States sees about 21 million cases annually; 800 will result in death. A norovirus outbreak can overwhelm local medical resources; the virus causes nearly 2 million outpatient visits and 400,000 emergency department visits each year. The combined annual cost reaches $2 billion, according to the CDC.

As federal employees, Dr. Hall and Ms. Barclay have no financial disclosures.

A test that can detect multiple causes of infectious gastroenteritis in one stool sample has been cleared for marketing by the Food and Drug Administration.

The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, is the "first test that can simultaneously detect 11 common viral, bacterial, and parasitic causes of infectious gastroenteritis from a single patient sample," the agency said in a Jan. 14 statement announcing the approval.

Courtesy CDC/Dr. Gilda Jones

The xTAG GPP tests for the bacteria Campylobacter, Clostridium difficile toxin A/B, Escherichia coli O157, enterotoxigenic E. coli (ETEC) LT/ST, Salmonella, Shigella, and Shiga-like toxin-producing E. coli (STEC) stx1/stx2; the viruses norovirus and rotavirus A; and the parasites Cryptosporidium and Giardia lamblia.

This test can help clinicians identify and treat the cause of gastroenteritis in patients more quickly, and "could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, said in the statement.

In studies conducted by the manufacturer, Luminex, results of the xTAG GPP were "comparable" with the results of individual tests for the 11 pathogens in stool samples from 1,407 patients with suspected infectious gastroenteritis, 313 samples from pediatric patients with suspected infectious gastroenteritis, and 203 samples from patients with confirmed cases of infectious gastroenteritis, according to the FDA. Because of the risk of false positives, "all positive results from the xTAG GPP need to be confirmed by additional testing," the agency’s announcement said.

The test, which is now available in the United States, can provide multiple results within 5 hours. It is the first and most comprehensive multiplexed product of its kind in the United States, according to a statement from Luminex.

The FDA cites data from the Centers for Disease Control and Prevention reporting that the number of deaths associated with gastroenteritis increased from nearly 7,000 to more than 17,000 per year between 1999 and 2007 in the United States. Two-thirds of the deaths were attributed to norovirus and C. difficile. 

e.mechcatie@elsevier.com

A test that can detect multiple causes of infectious gastroenteritis in one stool sample has been cleared for marketing by the Food and Drug Administration.

The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, is the "first test that can simultaneously detect 11 common viral, bacterial, and parasitic causes of infectious gastroenteritis from a single patient sample," the agency said in a Jan. 14 statement announcing the approval.

Courtesy CDC/Dr. Gilda Jones

The xTAG GPP tests for the bacteria Campylobacter, Clostridium difficile toxin A/B, Escherichia coli O157, enterotoxigenic E. coli (ETEC) LT/ST, Salmonella, Shigella, and Shiga-like toxin-producing E. coli (STEC) stx1/stx2; the viruses norovirus and rotavirus A; and the parasites Cryptosporidium and Giardia lamblia.

This test can help clinicians identify and treat the cause of gastroenteritis in patients more quickly, and "could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, said in the statement.

In studies conducted by the manufacturer, Luminex, results of the xTAG GPP were "comparable" with the results of individual tests for the 11 pathogens in stool samples from 1,407 patients with suspected infectious gastroenteritis, 313 samples from pediatric patients with suspected infectious gastroenteritis, and 203 samples from patients with confirmed cases of infectious gastroenteritis, according to the FDA. Because of the risk of false positives, "all positive results from the xTAG GPP need to be confirmed by additional testing," the agency’s announcement said.

The test, which is now available in the United States, can provide multiple results within 5 hours. It is the first and most comprehensive multiplexed product of its kind in the United States, according to a statement from Luminex.

The FDA cites data from the Centers for Disease Control and Prevention reporting that the number of deaths associated with gastroenteritis increased from nearly 7,000 to more than 17,000 per year between 1999 and 2007 in the United States. Two-thirds of the deaths were attributed to norovirus and C. difficile. 

e.mechcatie@elsevier.com

A test that can detect multiple causes of infectious gastroenteritis in one stool sample has been cleared for marketing by the Food and Drug Administration.

The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, is the "first test that can simultaneously detect 11 common viral, bacterial, and parasitic causes of infectious gastroenteritis from a single patient sample," the agency said in a Jan. 14 statement announcing the approval.

Courtesy CDC/Dr. Gilda Jones

The xTAG GPP tests for the bacteria Campylobacter, Clostridium difficile toxin A/B, Escherichia coli O157, enterotoxigenic E. coli (ETEC) LT/ST, Salmonella, Shigella, and Shiga-like toxin-producing E. coli (STEC) stx1/stx2; the viruses norovirus and rotavirus A; and the parasites Cryptosporidium and Giardia lamblia.

This test can help clinicians identify and treat the cause of gastroenteritis in patients more quickly, and "could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, said in the statement.

In studies conducted by the manufacturer, Luminex, results of the xTAG GPP were "comparable" with the results of individual tests for the 11 pathogens in stool samples from 1,407 patients with suspected infectious gastroenteritis, 313 samples from pediatric patients with suspected infectious gastroenteritis, and 203 samples from patients with confirmed cases of infectious gastroenteritis, according to the FDA. Because of the risk of false positives, "all positive results from the xTAG GPP need to be confirmed by additional testing," the agency’s announcement said.

The test, which is now available in the United States, can provide multiple results within 5 hours. It is the first and most comprehensive multiplexed product of its kind in the United States, according to a statement from Luminex.

The FDA cites data from the Centers for Disease Control and Prevention reporting that the number of deaths associated with gastroenteritis increased from nearly 7,000 to more than 17,000 per year between 1999 and 2007 in the United States. Two-thirds of the deaths were attributed to norovirus and C. difficile. 

e.mechcatie@elsevier.com

The infusion of donor feces into the duodenum of patients with recurrent, often intractable Clostridium difficile infection led to a much higher rate of cure than did either vancomycin therapy or bowel lavage in a small, randomized, open-label clinical trial.

The trial was closed early to new enrollment after only 43 of its planned 120 patients had undergone randomization because an interim analysis by the trial’s data safety and monitoring board found that almost all patients in the two control groups had a recurrence, compared with ultimate resolution of diarrhea in 15 of 16 patients treated with fecal infusion.

There were no infectious complications from the fecal infusions, and the only adverse event was transient diarrhea immediately following the procedure, which resolved in all patients within 3 hours, according to Dr. Els van Nood of the University of Amsterdam Academic Medical Center and her associates. They reported their findings online Jan. 16 in the New England Journal of Medicine.

"We found that the infusion of donor feces is a potential therapeutic strategy against recurrent C. difficile infection. In our study, infusion of a relatively large amount of feces through a nasoduodenal tube had an acceptable adverse-event profile and was logistically manageable," they noted.

Currently there is no effective therapy for recurrent C. difficile infection of the gastrointestinal tract. Extended and repeated courses of vancomycin usually are prescribed, but the antibiotic’s efficacy is estimated to be only 60% for the first recurrence and declines substantially with each subsequent recurrence.

The reason for the waning of antibiotic effectiveness is not known for certain. Experts have proposed that C. difficile spores may persist in the gut and get reactivated over time; that antibody responses to Clostridium toxins diminish over time; or that persistent disturbance of the native intestinal microbiota causes reduced diversity, which in turn reduces natural resistance to C. difficile.

It was hoped that infusion of feces from healthy donors would address the last mechanism, restoring the normal microbiota and boosting host defenses against C. difficile. Several preliminary studies have produced promising results, but "experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the unappealing nature of the treatment," Dr. van Nood and her colleagues said.

All the study subjects had persistent C. difficile infection, as evidenced by severe diarrhea with positive stool tests for the organism, after multiple courses of vancomycin and/or metronidazole.

Both patients and physicians are reluctant to choose donor-feces infusion until other measures have failed repeatedly. "It seems reasonable to initiate treatment with donor-feces infusion after the second or third relapse," the investigators wrote.

A total of 41 patients completed the study protocol. The trial compared the infusion of donor feces after pretreatment with a brief (4-day) course of vancomycin and bowel lavage (16 patients), a standard vancomycin regimen (12 patients), and a standard vancomycin regimen plus bowel lavage (13 patients). Bowel lavage was included because it has been used in previous studies of this new treatment and is thought to "reduce the pathogenic bowel content, facilitating colonization of healthy donor microbiota."

Most of the study subjects were elderly, with mean ages of 73 years, 66 years, and 69 years, respectively, in the three study arms.

Feces donors included 15 healthy volunteers aged 60 years and older who were screened for numerous potentially transmissible diseases. Fecal samples were collected just before the infusion was scheduled, and they were screened for parasites, C. difficile, and enteropathogenic bacteria. The samples were diluted with 500 mL of sterile saline, and the mixture was strained and poured into a sterile bottle.

A mean of 141 g of feces was infused through a nasoduodenal tube, and patients were monitored for 2 hours. Analysis of patients’ phylogenetic microarray profiles before and after treatment demonstrated "a major shift in the patients’ microbiota" from abnormal to normal diversity of organisms, Dr. van Nood and her associates said (N. Engl. J. Med. 2013 Jan. 16 [doi: 10.1056/NEJMoa1205037]).

The primary endpoint was cure without relapse within 10 weeks of treatment. Thirteen patients in the infusion group (81%) reached this endpoint after a single infusion. The remaining 3 patients had a second treatment, and 2 of them were cured, for an overall cure rate of 94% (15 of 16 patients).

In comparison, the cure rate with vancomycin alone was 31% (4 of 13 patients), and with vancomycin plus bowel lavage it was 23% (3 of 13).

At an interim follow-up of 5 weeks following initial treatment, C. difficile infection recurred in 1 patient (6%) in the infusion group, compared with 8 (62%) in the vancomycin-only group and 7 (54%) in the vancomycin-plus-lavage group.

Eighteen patients from the two control groups who relapsed after antibiotic treatment switched to off-protocol infusions of donor feces. Fifteen of them (83%) were cured: 11 after a single fecal infusion and 4 after two infusions.

All but one of the patients who received fecal infusions experienced immediate diarrhea, sometimes with cramping (31%) and belching (19%). These symptoms resolved in all of them within 3 hours. The only other adverse event that may have been related to the treatment was constipation, which developed in three patients.

Although the exact mechanism of action of this "unconventional" therapy is not yet known, Dr. van Nood and her colleagues speculated that donor-feces infusion probably restores the normal intestinal microbiota, enhancing the host defense against C. difficile.

Future research must determine the optimal protocol for donor-feces infusion, including the amount of feces required. Alternative routes of infusion, such as via enema or colonoscopy, also should be explored, they added.

This study was supported by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research. Four of the study’s 13 authors reported ties to Astellas. Two of those four also reported ties to Microbex.

The infusion of donor feces into the duodenum of patients with recurrent, often intractable Clostridium difficile infection led to a much higher rate of cure than did either vancomycin therapy or bowel lavage in a small, randomized, open-label clinical trial.

The trial was closed early to new enrollment after only 43 of its planned 120 patients had undergone randomization because an interim analysis by the trial’s data safety and monitoring board found that almost all patients in the two control groups had a recurrence, compared with ultimate resolution of diarrhea in 15 of 16 patients treated with fecal infusion.

There were no infectious complications from the fecal infusions, and the only adverse event was transient diarrhea immediately following the procedure, which resolved in all patients within 3 hours, according to Dr. Els van Nood of the University of Amsterdam Academic Medical Center and her associates. They reported their findings online Jan. 16 in the New England Journal of Medicine.

"We found that the infusion of donor feces is a potential therapeutic strategy against recurrent C. difficile infection. In our study, infusion of a relatively large amount of feces through a nasoduodenal tube had an acceptable adverse-event profile and was logistically manageable," they noted.

Currently there is no effective therapy for recurrent C. difficile infection of the gastrointestinal tract. Extended and repeated courses of vancomycin usually are prescribed, but the antibiotic’s efficacy is estimated to be only 60% for the first recurrence and declines substantially with each subsequent recurrence.

The reason for the waning of antibiotic effectiveness is not known for certain. Experts have proposed that C. difficile spores may persist in the gut and get reactivated over time; that antibody responses to Clostridium toxins diminish over time; or that persistent disturbance of the native intestinal microbiota causes reduced diversity, which in turn reduces natural resistance to C. difficile.

It was hoped that infusion of feces from healthy donors would address the last mechanism, restoring the normal microbiota and boosting host defenses against C. difficile. Several preliminary studies have produced promising results, but "experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the unappealing nature of the treatment," Dr. van Nood and her colleagues said.

All the study subjects had persistent C. difficile infection, as evidenced by severe diarrhea with positive stool tests for the organism, after multiple courses of vancomycin and/or metronidazole.

Both patients and physicians are reluctant to choose donor-feces infusion until other measures have failed repeatedly. "It seems reasonable to initiate treatment with donor-feces infusion after the second or third relapse," the investigators wrote.

A total of 41 patients completed the study protocol. The trial compared the infusion of donor feces after pretreatment with a brief (4-day) course of vancomycin and bowel lavage (16 patients), a standard vancomycin regimen (12 patients), and a standard vancomycin regimen plus bowel lavage (13 patients). Bowel lavage was included because it has been used in previous studies of this new treatment and is thought to "reduce the pathogenic bowel content, facilitating colonization of healthy donor microbiota."

Most of the study subjects were elderly, with mean ages of 73 years, 66 years, and 69 years, respectively, in the three study arms.

Feces donors included 15 healthy volunteers aged 60 years and older who were screened for numerous potentially transmissible diseases. Fecal samples were collected just before the infusion was scheduled, and they were screened for parasites, C. difficile, and enteropathogenic bacteria. The samples were diluted with 500 mL of sterile saline, and the mixture was strained and poured into a sterile bottle.

A mean of 141 g of feces was infused through a nasoduodenal tube, and patients were monitored for 2 hours. Analysis of patients’ phylogenetic microarray profiles before and after treatment demonstrated "a major shift in the patients’ microbiota" from abnormal to normal diversity of organisms, Dr. van Nood and her associates said (N. Engl. J. Med. 2013 Jan. 16 [doi: 10.1056/NEJMoa1205037]).

The primary endpoint was cure without relapse within 10 weeks of treatment. Thirteen patients in the infusion group (81%) reached this endpoint after a single infusion. The remaining 3 patients had a second treatment, and 2 of them were cured, for an overall cure rate of 94% (15 of 16 patients).

In comparison, the cure rate with vancomycin alone was 31% (4 of 13 patients), and with vancomycin plus bowel lavage it was 23% (3 of 13).

At an interim follow-up of 5 weeks following initial treatment, C. difficile infection recurred in 1 patient (6%) in the infusion group, compared with 8 (62%) in the vancomycin-only group and 7 (54%) in the vancomycin-plus-lavage group.

Eighteen patients from the two control groups who relapsed after antibiotic treatment switched to off-protocol infusions of donor feces. Fifteen of them (83%) were cured: 11 after a single fecal infusion and 4 after two infusions.

All but one of the patients who received fecal infusions experienced immediate diarrhea, sometimes with cramping (31%) and belching (19%). These symptoms resolved in all of them within 3 hours. The only other adverse event that may have been related to the treatment was constipation, which developed in three patients.

Although the exact mechanism of action of this "unconventional" therapy is not yet known, Dr. van Nood and her colleagues speculated that donor-feces infusion probably restores the normal intestinal microbiota, enhancing the host defense against C. difficile.

Future research must determine the optimal protocol for donor-feces infusion, including the amount of feces required. Alternative routes of infusion, such as via enema or colonoscopy, also should be explored, they added.

This study was supported by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research. Four of the study’s 13 authors reported ties to Astellas. Two of those four also reported ties to Microbex.

The infusion of donor feces into the duodenum of patients with recurrent, often intractable Clostridium difficile infection led to a much higher rate of cure than did either vancomycin therapy or bowel lavage in a small, randomized, open-label clinical trial.

The trial was closed early to new enrollment after only 43 of its planned 120 patients had undergone randomization because an interim analysis by the trial’s data safety and monitoring board found that almost all patients in the two control groups had a recurrence, compared with ultimate resolution of diarrhea in 15 of 16 patients treated with fecal infusion.

There were no infectious complications from the fecal infusions, and the only adverse event was transient diarrhea immediately following the procedure, which resolved in all patients within 3 hours, according to Dr. Els van Nood of the University of Amsterdam Academic Medical Center and her associates. They reported their findings online Jan. 16 in the New England Journal of Medicine.

"We found that the infusion of donor feces is a potential therapeutic strategy against recurrent C. difficile infection. In our study, infusion of a relatively large amount of feces through a nasoduodenal tube had an acceptable adverse-event profile and was logistically manageable," they noted.

Currently there is no effective therapy for recurrent C. difficile infection of the gastrointestinal tract. Extended and repeated courses of vancomycin usually are prescribed, but the antibiotic’s efficacy is estimated to be only 60% for the first recurrence and declines substantially with each subsequent recurrence.

The reason for the waning of antibiotic effectiveness is not known for certain. Experts have proposed that C. difficile spores may persist in the gut and get reactivated over time; that antibody responses to Clostridium toxins diminish over time; or that persistent disturbance of the native intestinal microbiota causes reduced diversity, which in turn reduces natural resistance to C. difficile.

It was hoped that infusion of feces from healthy donors would address the last mechanism, restoring the normal microbiota and boosting host defenses against C. difficile. Several preliminary studies have produced promising results, but "experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the unappealing nature of the treatment," Dr. van Nood and her colleagues said.

All the study subjects had persistent C. difficile infection, as evidenced by severe diarrhea with positive stool tests for the organism, after multiple courses of vancomycin and/or metronidazole.

Both patients and physicians are reluctant to choose donor-feces infusion until other measures have failed repeatedly. "It seems reasonable to initiate treatment with donor-feces infusion after the second or third relapse," the investigators wrote.

A total of 41 patients completed the study protocol. The trial compared the infusion of donor feces after pretreatment with a brief (4-day) course of vancomycin and bowel lavage (16 patients), a standard vancomycin regimen (12 patients), and a standard vancomycin regimen plus bowel lavage (13 patients). Bowel lavage was included because it has been used in previous studies of this new treatment and is thought to "reduce the pathogenic bowel content, facilitating colonization of healthy donor microbiota."

Most of the study subjects were elderly, with mean ages of 73 years, 66 years, and 69 years, respectively, in the three study arms.

Feces donors included 15 healthy volunteers aged 60 years and older who were screened for numerous potentially transmissible diseases. Fecal samples were collected just before the infusion was scheduled, and they were screened for parasites, C. difficile, and enteropathogenic bacteria. The samples were diluted with 500 mL of sterile saline, and the mixture was strained and poured into a sterile bottle.

A mean of 141 g of feces was infused through a nasoduodenal tube, and patients were monitored for 2 hours. Analysis of patients’ phylogenetic microarray profiles before and after treatment demonstrated "a major shift in the patients’ microbiota" from abnormal to normal diversity of organisms, Dr. van Nood and her associates said (N. Engl. J. Med. 2013 Jan. 16 [doi: 10.1056/NEJMoa1205037]).

The primary endpoint was cure without relapse within 10 weeks of treatment. Thirteen patients in the infusion group (81%) reached this endpoint after a single infusion. The remaining 3 patients had a second treatment, and 2 of them were cured, for an overall cure rate of 94% (15 of 16 patients).

In comparison, the cure rate with vancomycin alone was 31% (4 of 13 patients), and with vancomycin plus bowel lavage it was 23% (3 of 13).

At an interim follow-up of 5 weeks following initial treatment, C. difficile infection recurred in 1 patient (6%) in the infusion group, compared with 8 (62%) in the vancomycin-only group and 7 (54%) in the vancomycin-plus-lavage group.

Eighteen patients from the two control groups who relapsed after antibiotic treatment switched to off-protocol infusions of donor feces. Fifteen of them (83%) were cured: 11 after a single fecal infusion and 4 after two infusions.

All but one of the patients who received fecal infusions experienced immediate diarrhea, sometimes with cramping (31%) and belching (19%). These symptoms resolved in all of them within 3 hours. The only other adverse event that may have been related to the treatment was constipation, which developed in three patients.

Although the exact mechanism of action of this "unconventional" therapy is not yet known, Dr. van Nood and her colleagues speculated that donor-feces infusion probably restores the normal intestinal microbiota, enhancing the host defense against C. difficile.

Future research must determine the optimal protocol for donor-feces infusion, including the amount of feces required. Alternative routes of infusion, such as via enema or colonoscopy, also should be explored, they added.

This study was supported by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research. Four of the study’s 13 authors reported ties to Astellas. Two of those four also reported ties to Microbex.

Cyclosporine was no more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids, according to an open-label, randomized controlled trial of 115 patients.

However, the authors, led by Dr. David Laharie of the hepatology and gastroenterology service at Bordeaux (France) Hospital Center, said that their findings should be interpreted with caution because of the sample size. They added that treatment choice should be guided by physician and center experience.

As many as 40% of patients with acute severe ulcerative colitis who are admitted to the hospital are resistant to intravenous corticosteroids. For these patients, two drugs, cyclosporine or infliximab, have been used as rescue drugs to avoid colectomy.

Meanwhile, there haven’t been many studies comparing the two drugs. A 2012 systematic review of studies on cyclosporine and infliximab showed that the two were comparable, but randomized trials were needed, the review authors noted (Int. J. Colorectal. Dis. 2012 Nov. 1 [Epub ahead of print]). The current study, according to Dr. Laharie and his colleagues, is the first randomized trial to address the issue (Lancet 2012;380:1909-15).

For the 98-day open-label study, researchers randomized 115 patients to cyclosporine (58 patients) or infliximab (57). The patients were admitted for acute severe flare of ulcerative colitis (Lichtiger score greater than 10 points) to one of the 27 European centers participating in the study between June 1, 2007, and Aug. 31, 2010. They were 18 years or older (mean, 37.5 years), and had never received cyclosporine or infliximab. Contraception during the trial and for 3 months after was mandatory for patients of childbearing age.

The primary endpoint was treatment failure at any time, including absence of clinical response on day 7, relapse between day 7 and day 98, absence of steroid-free remission at day 98, or a severe adverse event leading to interruption of treatment, colectomy, or death. The secondary endpoints included clinical response at day 7, time to clinical response, mucosal healing at day 98, colectomy-free survival, and safety.

Treatment failed in 35 patients (60%) who were receiving cyclosporine, and in 31 patients (54%) who were given infliximab (absolute risk difference of 6%, P = .52). There were no significant differences between the two groups’ suboutcomes, such as responses at day 7 and colectomy rates at day 98. Both drugs were well tolerated, and there were no serious infections or deaths during the trial period.

The authors noted several limitations of the study. Treatment assignments were open label. The use of composite criteria as a primary outcome, rather than colectomy alone, "probably restricted the effect of unmasking on therapeutic decisions," they wrote. Also, the study was powered to detect a large difference between the effect of the two drugs. In addition, they said that because of the sample size, the study’s findings needed to be interpreted with caution.

The authors listed disclosures with several companies, including Merck Sharp & Dohme, Abbott, and Ferring, but they said that no commercial entity had any role in the study, and that the funding sources had no role in the study design, data collection, analysis, or interpretation.

n.miller@elsevier.com

On Twitter @naseemsmiller

Cyclosporine was no more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids, according to an open-label, randomized controlled trial of 115 patients.

However, the authors, led by Dr. David Laharie of the hepatology and gastroenterology service at Bordeaux (France) Hospital Center, said that their findings should be interpreted with caution because of the sample size. They added that treatment choice should be guided by physician and center experience.

As many as 40% of patients with acute severe ulcerative colitis who are admitted to the hospital are resistant to intravenous corticosteroids. For these patients, two drugs, cyclosporine or infliximab, have been used as rescue drugs to avoid colectomy.

Meanwhile, there haven’t been many studies comparing the two drugs. A 2012 systematic review of studies on cyclosporine and infliximab showed that the two were comparable, but randomized trials were needed, the review authors noted (Int. J. Colorectal. Dis. 2012 Nov. 1 [Epub ahead of print]). The current study, according to Dr. Laharie and his colleagues, is the first randomized trial to address the issue (Lancet 2012;380:1909-15).

For the 98-day open-label study, researchers randomized 115 patients to cyclosporine (58 patients) or infliximab (57). The patients were admitted for acute severe flare of ulcerative colitis (Lichtiger score greater than 10 points) to one of the 27 European centers participating in the study between June 1, 2007, and Aug. 31, 2010. They were 18 years or older (mean, 37.5 years), and had never received cyclosporine or infliximab. Contraception during the trial and for 3 months after was mandatory for patients of childbearing age.

The primary endpoint was treatment failure at any time, including absence of clinical response on day 7, relapse between day 7 and day 98, absence of steroid-free remission at day 98, or a severe adverse event leading to interruption of treatment, colectomy, or death. The secondary endpoints included clinical response at day 7, time to clinical response, mucosal healing at day 98, colectomy-free survival, and safety.

Treatment failed in 35 patients (60%) who were receiving cyclosporine, and in 31 patients (54%) who were given infliximab (absolute risk difference of 6%, P = .52). There were no significant differences between the two groups’ suboutcomes, such as responses at day 7 and colectomy rates at day 98. Both drugs were well tolerated, and there were no serious infections or deaths during the trial period.

The authors noted several limitations of the study. Treatment assignments were open label. The use of composite criteria as a primary outcome, rather than colectomy alone, "probably restricted the effect of unmasking on therapeutic decisions," they wrote. Also, the study was powered to detect a large difference between the effect of the two drugs. In addition, they said that because of the sample size, the study’s findings needed to be interpreted with caution.

The authors listed disclosures with several companies, including Merck Sharp & Dohme, Abbott, and Ferring, but they said that no commercial entity had any role in the study, and that the funding sources had no role in the study design, data collection, analysis, or interpretation.

n.miller@elsevier.com

On Twitter @naseemsmiller

Cyclosporine was no more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids, according to an open-label, randomized controlled trial of 115 patients.

However, the authors, led by Dr. David Laharie of the hepatology and gastroenterology service at Bordeaux (France) Hospital Center, said that their findings should be interpreted with caution because of the sample size. They added that treatment choice should be guided by physician and center experience.

As many as 40% of patients with acute severe ulcerative colitis who are admitted to the hospital are resistant to intravenous corticosteroids. For these patients, two drugs, cyclosporine or infliximab, have been used as rescue drugs to avoid colectomy.

Meanwhile, there haven’t been many studies comparing the two drugs. A 2012 systematic review of studies on cyclosporine and infliximab showed that the two were comparable, but randomized trials were needed, the review authors noted (Int. J. Colorectal. Dis. 2012 Nov. 1 [Epub ahead of print]). The current study, according to Dr. Laharie and his colleagues, is the first randomized trial to address the issue (Lancet 2012;380:1909-15).

For the 98-day open-label study, researchers randomized 115 patients to cyclosporine (58 patients) or infliximab (57). The patients were admitted for acute severe flare of ulcerative colitis (Lichtiger score greater than 10 points) to one of the 27 European centers participating in the study between June 1, 2007, and Aug. 31, 2010. They were 18 years or older (mean, 37.5 years), and had never received cyclosporine or infliximab. Contraception during the trial and for 3 months after was mandatory for patients of childbearing age.

The primary endpoint was treatment failure at any time, including absence of clinical response on day 7, relapse between day 7 and day 98, absence of steroid-free remission at day 98, or a severe adverse event leading to interruption of treatment, colectomy, or death. The secondary endpoints included clinical response at day 7, time to clinical response, mucosal healing at day 98, colectomy-free survival, and safety.

Treatment failed in 35 patients (60%) who were receiving cyclosporine, and in 31 patients (54%) who were given infliximab (absolute risk difference of 6%, P = .52). There were no significant differences between the two groups’ suboutcomes, such as responses at day 7 and colectomy rates at day 98. Both drugs were well tolerated, and there were no serious infections or deaths during the trial period.

The authors noted several limitations of the study. Treatment assignments were open label. The use of composite criteria as a primary outcome, rather than colectomy alone, "probably restricted the effect of unmasking on therapeutic decisions," they wrote. Also, the study was powered to detect a large difference between the effect of the two drugs. In addition, they said that because of the sample size, the study’s findings needed to be interpreted with caution.

The authors listed disclosures with several companies, including Merck Sharp & Dohme, Abbott, and Ferring, but they said that no commercial entity had any role in the study, and that the funding sources had no role in the study design, data collection, analysis, or interpretation.

n.miller@elsevier.com

On Twitter @naseemsmiller

Assessment of colonic transit in a patient presenting with constipation is recommended only after excluding a defecatory disorder and after treatment with laxatives and first-line pharmacologic agents fails, or after pelvic floor training in those with a defecatory disorder fails, according to a new medical position statement from the American Gastroenterological Association.

This recommendation is in contrast to the previous AGA medical position statement on constipation, which called for earlier assessment for colonic transit.

The change is one of only three substantive changes to the statement, which is published in the January issue of Gastroenterology; the others are the use of GRADE (Grading of Recommendations Assessment, Development, and Evaluation), which rates for each recommendation, its strength and quality of evidence, and the inclusion of newer agents; and deletion of certain older agents in treatment recommendations.

The colonic transit assessment recommendation is based in part on concerns about potential long-term side effects associated with newer agents that might be prescribed in patients with slow colonic transit.

"At present, the medical approaches used for managing normal and slow-transit constipation are similar. However, the major pharmacological trials in chronic constipation did not assess if the response to therapy is influenced by colonic transit. While newer agents may also be considered without assessing colonic transit, the long-term side effects, if any, of these agents are unknown and exposure to such potential risks might be more appropriate in patients with the more severe forms of constipation associated with slow transit," according to the statement.

Also, up to 50% of all patients with defecatory disorders have slow colonic transit as well, thus slow colonic transit does not exclude a defecatory disorder – and it also does not alter the management of defecatory disorders.

As for the approach to assessing for slow transit once a defecatory disorder is excluded, the statement says, "consideration should be given to assessing colonic transit by radiopaque markers, scintigraphy, or a wireless motility capsule in patients with persistent symptoms on laxatives."

Identifying slow colonic transit can reassure patients about the pathophysiology of their symptoms and also can serve as an objective marker for documenting response to treatment and provide physicians with the appropriate rationale for prescribing newer, often more expensive treatments.

Recommendations in the AGA statement that address the initial clinical assessment of constipation include the following:

• When feasible, medications that can cause constipation should be discontinued before further testing is initiated. This is a "strong" recommendation based on low-quality evidence.

• A careful digital rectal examination, including assessment of pelvic floor motion during simulated evacuation, is preferable to a cursory examination without these maneuvers and should be performed prior to referral for anorectal manometry. A normal exam, however, does not exclude defecatory disorders. This is a "strong" recommendation based on moderate-quality evidence.

The recommendations also address testing to assess medical causes of constipation. In addition to colonic transit testing, after ruling out a defecatory disorder, other recommended tests to assess for medical causes of constipation include a complete red blood count. Metabolic tests such as glucose, calcium, and sensitive thyroid-stimulating hormone are necessary only when other clinical features warrant these tests, and a colonoscopy and an imaging procedure for colonic lesions is only necessary in the presence of "alarm features," including blood in the stool, anemia, and weight loss, for medically refractory constipation or when age-appropriate colon cancer screening has not been performed. Anorectal manometry and a rectal balloon expulsion are indicated in those who fail to respond to laxatives but defecography only when anorectal manometry and a rectal balloon expulsion are inconclusive for defecatory disorders. All of these are "strong" recommendations based on low- or moderate-quality evidence.

Initial medical management, according to the statement, should include:

• A therapeutic trial of fiber supplementation and/or osmotic or stimulant laxatives after discontinuing medications that can cause constipation and after performing blood and other tests as guided by clinical features, but before anorectal testing.

• Use of long-term laxatives for normal and slow-transit constipation.

• Anorectal testing in patients who do not respond to these measures.

• Pelvic floor retraining by biofeedback therapy rather than laxatives in those with defecatory disorders.

These are all "strong" recommendations based on moderate- or high-quality evidence.

As for treatments to consider in patients who fail to respond to initial approaches, the AGA says that newer agents, such as lubiprostone and linaclotide, should be considered in those with normal or slow transit constipation who fail to respond to simple laxatives. Based on the GRADE ratings, this is a "weak" recommendation (implying that benefits, risks, and the burden of intervention are balanced among several legitimate management options or that appreciable uncertainty exists, and is based on moderate-quality evidence).

Also, when symptoms persist despite an adequate trial of biofeedback therapy – which improves symptoms in more than 70% of patients with defecatory disorders – anorectal tests and colonic transit should be reevaluated. This is a "strong" recommendation based on low-quality evidence.

Subtotal colectomy, as opposed to chronic laxative therapy, should be considered in those with symptomatic slow-transit constipation without a defecatory disorder, and colonic intraluminal testing should be considered to document colonic motor dysfunction prior to colectomy. These are weak recommendations based on moderate-quality evidence.

Finally, suppositories or enemas, rather than oral laxatives alone, should be considered in those with refractory pelvic floor dysfunction. This is a weak recommendation based on low-quality evidence.

These recommendations, drafted by a medical position panel and ultimately approved by the AGA Institute Governing Board, were published in conjunction with a technical review, which provides the rationale for the recommendations included in the statement.

AGA Institute Medical Position Panel members listed the following disclosures: Dr. Anthony Lembo reported serving as a consultant to, and serving as an advisory board member for Ironwood Pharmaceuticals and Forest Laboratories; Dr. Spencer D. Dorn reported serving as a consultant to Ironwood Pharmaceuticals and Forest Laboratories, and receiving research support from these companies, as well as from Synergy Pharmaceutical and Takeda Pharmaceuticals; Dr. A. E. Bharucha reported having a financial interest in a new technology related to anal manometry and serving a consultant for Helsin Therapeutics and Asubio Pharmaceuticals.

Assessment of colonic transit in a patient presenting with constipation is recommended only after excluding a defecatory disorder and after treatment with laxatives and first-line pharmacologic agents fails, or after pelvic floor training in those with a defecatory disorder fails, according to a new medical position statement from the American Gastroenterological Association.

This recommendation is in contrast to the previous AGA medical position statement on constipation, which called for earlier assessment for colonic transit.

The change is one of only three substantive changes to the statement, which is published in the January issue of Gastroenterology; the others are the use of GRADE (Grading of Recommendations Assessment, Development, and Evaluation), which rates for each recommendation, its strength and quality of evidence, and the inclusion of newer agents; and deletion of certain older agents in treatment recommendations.

The colonic transit assessment recommendation is based in part on concerns about potential long-term side effects associated with newer agents that might be prescribed in patients with slow colonic transit.

"At present, the medical approaches used for managing normal and slow-transit constipation are similar. However, the major pharmacological trials in chronic constipation did not assess if the response to therapy is influenced by colonic transit. While newer agents may also be considered without assessing colonic transit, the long-term side effects, if any, of these agents are unknown and exposure to such potential risks might be more appropriate in patients with the more severe forms of constipation associated with slow transit," according to the statement.

Also, up to 50% of all patients with defecatory disorders have slow colonic transit as well, thus slow colonic transit does not exclude a defecatory disorder – and it also does not alter the management of defecatory disorders.

As for the approach to assessing for slow transit once a defecatory disorder is excluded, the statement says, "consideration should be given to assessing colonic transit by radiopaque markers, scintigraphy, or a wireless motility capsule in patients with persistent symptoms on laxatives."

Identifying slow colonic transit can reassure patients about the pathophysiology of their symptoms and also can serve as an objective marker for documenting response to treatment and provide physicians with the appropriate rationale for prescribing newer, often more expensive treatments.

Recommendations in the AGA statement that address the initial clinical assessment of constipation include the following:

• When feasible, medications that can cause constipation should be discontinued before further testing is initiated. This is a "strong" recommendation based on low-quality evidence.

• A careful digital rectal examination, including assessment of pelvic floor motion during simulated evacuation, is preferable to a cursory examination without these maneuvers and should be performed prior to referral for anorectal manometry. A normal exam, however, does not exclude defecatory disorders. This is a "strong" recommendation based on moderate-quality evidence.

The recommendations also address testing to assess medical causes of constipation. In addition to colonic transit testing, after ruling out a defecatory disorder, other recommended tests to assess for medical causes of constipation include a complete red blood count. Metabolic tests such as glucose, calcium, and sensitive thyroid-stimulating hormone are necessary only when other clinical features warrant these tests, and a colonoscopy and an imaging procedure for colonic lesions is only necessary in the presence of "alarm features," including blood in the stool, anemia, and weight loss, for medically refractory constipation or when age-appropriate colon cancer screening has not been performed. Anorectal manometry and a rectal balloon expulsion are indicated in those who fail to respond to laxatives but defecography only when anorectal manometry and a rectal balloon expulsion are inconclusive for defecatory disorders. All of these are "strong" recommendations based on low- or moderate-quality evidence.

Initial medical management, according to the statement, should include:

• A therapeutic trial of fiber supplementation and/or osmotic or stimulant laxatives after discontinuing medications that can cause constipation and after performing blood and other tests as guided by clinical features, but before anorectal testing.

• Use of long-term laxatives for normal and slow-transit constipation.

• Anorectal testing in patients who do not respond to these measures.

• Pelvic floor retraining by biofeedback therapy rather than laxatives in those with defecatory disorders.

These are all "strong" recommendations based on moderate- or high-quality evidence.

As for treatments to consider in patients who fail to respond to initial approaches, the AGA says that newer agents, such as lubiprostone and linaclotide, should be considered in those with normal or slow transit constipation who fail to respond to simple laxatives. Based on the GRADE ratings, this is a "weak" recommendation (implying that benefits, risks, and the burden of intervention are balanced among several legitimate management options or that appreciable uncertainty exists, and is based on moderate-quality evidence).

Also, when symptoms persist despite an adequate trial of biofeedback therapy – which improves symptoms in more than 70% of patients with defecatory disorders – anorectal tests and colonic transit should be reevaluated. This is a "strong" recommendation based on low-quality evidence.

Subtotal colectomy, as opposed to chronic laxative therapy, should be considered in those with symptomatic slow-transit constipation without a defecatory disorder, and colonic intraluminal testing should be considered to document colonic motor dysfunction prior to colectomy. These are weak recommendations based on moderate-quality evidence.

Finally, suppositories or enemas, rather than oral laxatives alone, should be considered in those with refractory pelvic floor dysfunction. This is a weak recommendation based on low-quality evidence.

These recommendations, drafted by a medical position panel and ultimately approved by the AGA Institute Governing Board, were published in conjunction with a technical review, which provides the rationale for the recommendations included in the statement.

AGA Institute Medical Position Panel members listed the following disclosures: Dr. Anthony Lembo reported serving as a consultant to, and serving as an advisory board member for Ironwood Pharmaceuticals and Forest Laboratories; Dr. Spencer D. Dorn reported serving as a consultant to Ironwood Pharmaceuticals and Forest Laboratories, and receiving research support from these companies, as well as from Synergy Pharmaceutical and Takeda Pharmaceuticals; Dr. A. E. Bharucha reported having a financial interest in a new technology related to anal manometry and serving a consultant for Helsin Therapeutics and Asubio Pharmaceuticals.

Assessment of colonic transit in a patient presenting with constipation is recommended only after excluding a defecatory disorder and after treatment with laxatives and first-line pharmacologic agents fails, or after pelvic floor training in those with a defecatory disorder fails, according to a new medical position statement from the American Gastroenterological Association.

This recommendation is in contrast to the previous AGA medical position statement on constipation, which called for earlier assessment for colonic transit.

The change is one of only three substantive changes to the statement, which is published in the January issue of Gastroenterology; the others are the use of GRADE (Grading of Recommendations Assessment, Development, and Evaluation), which rates for each recommendation, its strength and quality of evidence, and the inclusion of newer agents; and deletion of certain older agents in treatment recommendations.

The colonic transit assessment recommendation is based in part on concerns about potential long-term side effects associated with newer agents that might be prescribed in patients with slow colonic transit.

"At present, the medical approaches used for managing normal and slow-transit constipation are similar. However, the major pharmacological trials in chronic constipation did not assess if the response to therapy is influenced by colonic transit. While newer agents may also be considered without assessing colonic transit, the long-term side effects, if any, of these agents are unknown and exposure to such potential risks might be more appropriate in patients with the more severe forms of constipation associated with slow transit," according to the statement.

Also, up to 50% of all patients with defecatory disorders have slow colonic transit as well, thus slow colonic transit does not exclude a defecatory disorder – and it also does not alter the management of defecatory disorders.

As for the approach to assessing for slow transit once a defecatory disorder is excluded, the statement says, "consideration should be given to assessing colonic transit by radiopaque markers, scintigraphy, or a wireless motility capsule in patients with persistent symptoms on laxatives."

Identifying slow colonic transit can reassure patients about the pathophysiology of their symptoms and also can serve as an objective marker for documenting response to treatment and provide physicians with the appropriate rationale for prescribing newer, often more expensive treatments.

Recommendations in the AGA statement that address the initial clinical assessment of constipation include the following:

• When feasible, medications that can cause constipation should be discontinued before further testing is initiated. This is a "strong" recommendation based on low-quality evidence.

• A careful digital rectal examination, including assessment of pelvic floor motion during simulated evacuation, is preferable to a cursory examination without these maneuvers and should be performed prior to referral for anorectal manometry. A normal exam, however, does not exclude defecatory disorders. This is a "strong" recommendation based on moderate-quality evidence.

The recommendations also address testing to assess medical causes of constipation. In addition to colonic transit testing, after ruling out a defecatory disorder, other recommended tests to assess for medical causes of constipation include a complete red blood count. Metabolic tests such as glucose, calcium, and sensitive thyroid-stimulating hormone are necessary only when other clinical features warrant these tests, and a colonoscopy and an imaging procedure for colonic lesions is only necessary in the presence of "alarm features," including blood in the stool, anemia, and weight loss, for medically refractory constipation or when age-appropriate colon cancer screening has not been performed. Anorectal manometry and a rectal balloon expulsion are indicated in those who fail to respond to laxatives but defecography only when anorectal manometry and a rectal balloon expulsion are inconclusive for defecatory disorders. All of these are "strong" recommendations based on low- or moderate-quality evidence.

Initial medical management, according to the statement, should include:

• A therapeutic trial of fiber supplementation and/or osmotic or stimulant laxatives after discontinuing medications that can cause constipation and after performing blood and other tests as guided by clinical features, but before anorectal testing.

• Use of long-term laxatives for normal and slow-transit constipation.

• Anorectal testing in patients who do not respond to these measures.

• Pelvic floor retraining by biofeedback therapy rather than laxatives in those with defecatory disorders.

These are all "strong" recommendations based on moderate- or high-quality evidence.

As for treatments to consider in patients who fail to respond to initial approaches, the AGA says that newer agents, such as lubiprostone and linaclotide, should be considered in those with normal or slow transit constipation who fail to respond to simple laxatives. Based on the GRADE ratings, this is a "weak" recommendation (implying that benefits, risks, and the burden of intervention are balanced among several legitimate management options or that appreciable uncertainty exists, and is based on moderate-quality evidence).

Also, when symptoms persist despite an adequate trial of biofeedback therapy – which improves symptoms in more than 70% of patients with defecatory disorders – anorectal tests and colonic transit should be reevaluated. This is a "strong" recommendation based on low-quality evidence.

Subtotal colectomy, as opposed to chronic laxative therapy, should be considered in those with symptomatic slow-transit constipation without a defecatory disorder, and colonic intraluminal testing should be considered to document colonic motor dysfunction prior to colectomy. These are weak recommendations based on moderate-quality evidence.

Finally, suppositories or enemas, rather than oral laxatives alone, should be considered in those with refractory pelvic floor dysfunction. This is a weak recommendation based on low-quality evidence.

These recommendations, drafted by a medical position panel and ultimately approved by the AGA Institute Governing Board, were published in conjunction with a technical review, which provides the rationale for the recommendations included in the statement.

AGA Institute Medical Position Panel members listed the following disclosures: Dr. Anthony Lembo reported serving as a consultant to, and serving as an advisory board member for Ironwood Pharmaceuticals and Forest Laboratories; Dr. Spencer D. Dorn reported serving as a consultant to Ironwood Pharmaceuticals and Forest Laboratories, and receiving research support from these companies, as well as from Synergy Pharmaceutical and Takeda Pharmaceuticals; Dr. A. E. Bharucha reported having a financial interest in a new technology related to anal manometry and serving a consultant for Helsin Therapeutics and Asubio Pharmaceuticals.

Depressive symptoms were associated with a doubling of the risk of Crohn’s disease in two large prospective cohorts of women, Dr. Ashwin N. Ananthakrishnan and his colleagues reported in the January issue of Clinical Gastroenterology and Hepatology (2013;11:57-62).

For women with recent and past episodes of depressive symptoms, the associations with the development of Crohn’s disease were significant, and were stronger for those with recent depression. The effect sizes were "in the same range we found for current smoking, oral contraceptive use, and NSAID use," all of which are known risk factors for Crohn’s disease, said Dr. Ananthakrishnan of Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

Video Source: American Gastroenterological Association YouTube channe

"Our findings support the potential importance of a biopsychosocial model in the pathogenesis of Crohn’s disease, and suggest the need for further studies on the effect of depression and stress on immune function and regulation," they noted.

Depression and life stress long have been thought to contribute to immune dysfunction and to influence both the risk for and the course of immune-mediated disorders such as Crohn’s. But until now, few studies have examined the role of mood in the onset of Crohn’s disease and ulcerative colitis, and those that did so were retrospective, failed to adjust for possible confounders, and assessed only the occurrence of major life stressors rather than the presence of depressive symptoms.

To address these shortcomings, the investigators examined the link between depressive symptoms and later onset of Crohn’s disease and ulcerative colitis using data from the prospective Nurses Health Study I and II. NHS I enrolled 121,700 female registered nurses who were 30-55 years old at baseline in 1976, and NHS II enrolled 116,686 female RNs aged 25-42 years at baseline in 1989.

For this study, Dr. Ananthakrishnan and his colleagues analyzed data for 152,461 of these participants in the two NHS cohorts. A total of 170 developed incident Crohn’s disease and 203 developed incident ulcerative colitis during follow-up.

Depressive symptoms were assessed several times in both the NHS I and II subjects using the five-question Mental Health Index (MHI-5), a subscale of the Short Form 36 health status survey. The participants received scores ranging from 1 to 100; 16,986 women (11% of the study population) received scores of 0-52, indicating the presence of depressive symptoms.

Subjects who scored from 86 to 100 composed the reference group.

The data were adjusted to account for numerous covariates that might influence risk for Crohn’s disease and ulcerative colitis, including the subjects’ race/ethnicity; smoking status; weight; menopausal status; and use of oral contraceptives, hormone therapy, and aspirin or NSAIDs.

There was a significant and linear increase in the risk of developing Crohn’s disease as MHI-5 scores decreased. Compared with the reference group, women with an MHI-5 score of 76-85 had a hazard ratio for Crohn’s disease of 1.38, those with an MHI-5 score of 53-75 had an HR of 1.59, and women with depressive symptoms and a score of 0-52 had an HR of 2.36.

No such association was seen between depressive symptoms and ulcerative colitis.

To account for the possibility that the study subjects’ depressed mood might be due to as-yet undiagnosed GI symptoms, the researchers performed a "lag" analysis excluding all cases of Crohn’s and ulcerative colitis that developed within 2 years of MHI-5 assessment. The results were unchanged in this analysis, they said.

The investigators also performed a sensitivity analysis restricted only to cases of Crohn’s disease that developed after 1996, when the NHS subjects first were routinely questioned about their use of antidepressant medications. Adjusting for the use of these drugs only slightly attenuated the strong association between depressive symptoms and Crohn’s disease.

"Preliminary animal and human studies suggest that treating depression through administration of antidepressants, or through improvement in coping mechanisms, could reduce risk of disease relapse. Whether similar interventions can also influence risk of disease onset, particularly among individuals with genetic susceptibility for Crohn’s disease or ulcerative colitis, merits further study," Dr. Ananthakrishnan and his associates said.

This study was supported by the American Gastroenterological Association, the Crohn’s and Colitis Foundation of America, the Broad Foundation, and the National Institutes of Health. Dr. Ananthakrishnan reported no potential financial conflicts of interest; his associates reported ties to Policy Analysis, Bayer HealthCare, Millennium Pharmaceuticals, and Pfizer.

Depressive symptoms were associated with a doubling of the risk of Crohn’s disease in two large prospective cohorts of women, Dr. Ashwin N. Ananthakrishnan and his colleagues reported in the January issue of Clinical Gastroenterology and Hepatology (2013;11:57-62).

For women with recent and past episodes of depressive symptoms, the associations with the development of Crohn’s disease were significant, and were stronger for those with recent depression. The effect sizes were "in the same range we found for current smoking, oral contraceptive use, and NSAID use," all of which are known risk factors for Crohn’s disease, said Dr. Ananthakrishnan of Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

Video Source: American Gastroenterological Association YouTube channe

"Our findings support the potential importance of a biopsychosocial model in the pathogenesis of Crohn’s disease, and suggest the need for further studies on the effect of depression and stress on immune function and regulation," they noted.

Depression and life stress long have been thought to contribute to immune dysfunction and to influence both the risk for and the course of immune-mediated disorders such as Crohn’s. But until now, few studies have examined the role of mood in the onset of Crohn’s disease and ulcerative colitis, and those that did so were retrospective, failed to adjust for possible confounders, and assessed only the occurrence of major life stressors rather than the presence of depressive symptoms.

To address these shortcomings, the investigators examined the link between depressive symptoms and later onset of Crohn’s disease and ulcerative colitis using data from the prospective Nurses Health Study I and II. NHS I enrolled 121,700 female registered nurses who were 30-55 years old at baseline in 1976, and NHS II enrolled 116,686 female RNs aged 25-42 years at baseline in 1989.

For this study, Dr. Ananthakrishnan and his colleagues analyzed data for 152,461 of these participants in the two NHS cohorts. A total of 170 developed incident Crohn’s disease and 203 developed incident ulcerative colitis during follow-up.

Depressive symptoms were assessed several times in both the NHS I and II subjects using the five-question Mental Health Index (MHI-5), a subscale of the Short Form 36 health status survey. The participants received scores ranging from 1 to 100; 16,986 women (11% of the study population) received scores of 0-52, indicating the presence of depressive symptoms.

Subjects who scored from 86 to 100 composed the reference group.

The data were adjusted to account for numerous covariates that might influence risk for Crohn’s disease and ulcerative colitis, including the subjects’ race/ethnicity; smoking status; weight; menopausal status; and use of oral contraceptives, hormone therapy, and aspirin or NSAIDs.

There was a significant and linear increase in the risk of developing Crohn’s disease as MHI-5 scores decreased. Compared with the reference group, women with an MHI-5 score of 76-85 had a hazard ratio for Crohn’s disease of 1.38, those with an MHI-5 score of 53-75 had an HR of 1.59, and women with depressive symptoms and a score of 0-52 had an HR of 2.36.

No such association was seen between depressive symptoms and ulcerative colitis.

To account for the possibility that the study subjects’ depressed mood might be due to as-yet undiagnosed GI symptoms, the researchers performed a "lag" analysis excluding all cases of Crohn’s and ulcerative colitis that developed within 2 years of MHI-5 assessment. The results were unchanged in this analysis, they said.

The investigators also performed a sensitivity analysis restricted only to cases of Crohn’s disease that developed after 1996, when the NHS subjects first were routinely questioned about their use of antidepressant medications. Adjusting for the use of these drugs only slightly attenuated the strong association between depressive symptoms and Crohn’s disease.

"Preliminary animal and human studies suggest that treating depression through administration of antidepressants, or through improvement in coping mechanisms, could reduce risk of disease relapse. Whether similar interventions can also influence risk of disease onset, particularly among individuals with genetic susceptibility for Crohn’s disease or ulcerative colitis, merits further study," Dr. Ananthakrishnan and his associates said.

This study was supported by the American Gastroenterological Association, the Crohn’s and Colitis Foundation of America, the Broad Foundation, and the National Institutes of Health. Dr. Ananthakrishnan reported no potential financial conflicts of interest; his associates reported ties to Policy Analysis, Bayer HealthCare, Millennium Pharmaceuticals, and Pfizer.

Depressive symptoms were associated with a doubling of the risk of Crohn’s disease in two large prospective cohorts of women, Dr. Ashwin N. Ananthakrishnan and his colleagues reported in the January issue of Clinical Gastroenterology and Hepatology (2013;11:57-62).

For women with recent and past episodes of depressive symptoms, the associations with the development of Crohn’s disease were significant, and were stronger for those with recent depression. The effect sizes were "in the same range we found for current smoking, oral contraceptive use, and NSAID use," all of which are known risk factors for Crohn’s disease, said Dr. Ananthakrishnan of Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

Video Source: American Gastroenterological Association YouTube channe

"Our findings support the potential importance of a biopsychosocial model in the pathogenesis of Crohn’s disease, and suggest the need for further studies on the effect of depression and stress on immune function and regulation," they noted.

Depression and life stress long have been thought to contribute to immune dysfunction and to influence both the risk for and the course of immune-mediated disorders such as Crohn’s. But until now, few studies have examined the role of mood in the onset of Crohn’s disease and ulcerative colitis, and those that did so were retrospective, failed to adjust for possible confounders, and assessed only the occurrence of major life stressors rather than the presence of depressive symptoms.

To address these shortcomings, the investigators examined the link between depressive symptoms and later onset of Crohn’s disease and ulcerative colitis using data from the prospective Nurses Health Study I and II. NHS I enrolled 121,700 female registered nurses who were 30-55 years old at baseline in 1976, and NHS II enrolled 116,686 female RNs aged 25-42 years at baseline in 1989.

For this study, Dr. Ananthakrishnan and his colleagues analyzed data for 152,461 of these participants in the two NHS cohorts. A total of 170 developed incident Crohn’s disease and 203 developed incident ulcerative colitis during follow-up.

Depressive symptoms were assessed several times in both the NHS I and II subjects using the five-question Mental Health Index (MHI-5), a subscale of the Short Form 36 health status survey. The participants received scores ranging from 1 to 100; 16,986 women (11% of the study population) received scores of 0-52, indicating the presence of depressive symptoms.

Subjects who scored from 86 to 100 composed the reference group.

The data were adjusted to account for numerous covariates that might influence risk for Crohn’s disease and ulcerative colitis, including the subjects’ race/ethnicity; smoking status; weight; menopausal status; and use of oral contraceptives, hormone therapy, and aspirin or NSAIDs.

There was a significant and linear increase in the risk of developing Crohn’s disease as MHI-5 scores decreased. Compared with the reference group, women with an MHI-5 score of 76-85 had a hazard ratio for Crohn’s disease of 1.38, those with an MHI-5 score of 53-75 had an HR of 1.59, and women with depressive symptoms and a score of 0-52 had an HR of 2.36.

No such association was seen between depressive symptoms and ulcerative colitis.

To account for the possibility that the study subjects’ depressed mood might be due to as-yet undiagnosed GI symptoms, the researchers performed a "lag" analysis excluding all cases of Crohn’s and ulcerative colitis that developed within 2 years of MHI-5 assessment. The results were unchanged in this analysis, they said.

The investigators also performed a sensitivity analysis restricted only to cases of Crohn’s disease that developed after 1996, when the NHS subjects first were routinely questioned about their use of antidepressant medications. Adjusting for the use of these drugs only slightly attenuated the strong association between depressive symptoms and Crohn’s disease.

"Preliminary animal and human studies suggest that treating depression through administration of antidepressants, or through improvement in coping mechanisms, could reduce risk of disease relapse. Whether similar interventions can also influence risk of disease onset, particularly among individuals with genetic susceptibility for Crohn’s disease or ulcerative colitis, merits further study," Dr. Ananthakrishnan and his associates said.

This study was supported by the American Gastroenterological Association, the Crohn’s and Colitis Foundation of America, the Broad Foundation, and the National Institutes of Health. Dr. Ananthakrishnan reported no potential financial conflicts of interest; his associates reported ties to Policy Analysis, Bayer HealthCare, Millennium Pharmaceuticals, and Pfizer.

The Food and Drug Administration on Dec. 21 approved teduglutide, to be marketed under the trade name Gattex, to treat adults with short bowel syndrome (SBS) who need parenteral nutrition.

Teduglutide, a recombinant analogue of human glucagon-like peptide-2 (GLP-2), was unanimously recommended for approval by an FDA advisory panel in October. It is a once-daily subcutaneous injection that helps improve intestinal absorption of fluids and nutrients, reducing the frequency and volume of parenteral nutrition.

"Considering Gattex has been shown to significantly reduce or in some cases even eliminate the requirement for parenteral support, it may become a cornerstone therapy in the management of short bowel syndrome." Dr. Ken Fujioka of the Nutrition and Metabolic Research Center, Scripps Clinic, Del Mar, Calif., said in a statement issued by Gattex’s maker, NPA Pharmaceuticals.

It is the third drug to be approved by the FDA for SBS patients who are dependent on parenteral nutrition. Somatropin (Zorbtive) was approved in 2003 and glutamine (Nutrestore) in 2004.

"Today’s approval expands the available treatment options for patients with this life-threatening condition," Dr. Victoria Kusiak, deputy director of the Office of Drug Evaluation III in the FDA Center for Drug Evaluation and Research, said in a statement. "Because Gattex may cause other serious health conditions, it is critical that patients and health care professionals understand the drug’s potential and known safety risks."

Teduglutide therapy increases the risk of developing cancer and polyps in the intestine, obstructions in the intestine, gallbladder disease, biliary tract disease, and pancreatic disease. The drug will have a Risk Evaluation and Mitigation Strategy, consisting of a communication plan and training for prescribers, according to the FDA.

Pivotal data on the drug were published in September in Gastroenterology (Gastroenterology 2012 Sept. 13 [doi:10.1053/j.gastro.2012.09.007]).

The Food and Drug Administration on Dec. 21 approved teduglutide, to be marketed under the trade name Gattex, to treat adults with short bowel syndrome (SBS) who need parenteral nutrition.

Teduglutide, a recombinant analogue of human glucagon-like peptide-2 (GLP-2), was unanimously recommended for approval by an FDA advisory panel in October. It is a once-daily subcutaneous injection that helps improve intestinal absorption of fluids and nutrients, reducing the frequency and volume of parenteral nutrition.

"Considering Gattex has been shown to significantly reduce or in some cases even eliminate the requirement for parenteral support, it may become a cornerstone therapy in the management of short bowel syndrome." Dr. Ken Fujioka of the Nutrition and Metabolic Research Center, Scripps Clinic, Del Mar, Calif., said in a statement issued by Gattex’s maker, NPA Pharmaceuticals.

It is the third drug to be approved by the FDA for SBS patients who are dependent on parenteral nutrition. Somatropin (Zorbtive) was approved in 2003 and glutamine (Nutrestore) in 2004.

"Today’s approval expands the available treatment options for patients with this life-threatening condition," Dr. Victoria Kusiak, deputy director of the Office of Drug Evaluation III in the FDA Center for Drug Evaluation and Research, said in a statement. "Because Gattex may cause other serious health conditions, it is critical that patients and health care professionals understand the drug’s potential and known safety risks."

Teduglutide therapy increases the risk of developing cancer and polyps in the intestine, obstructions in the intestine, gallbladder disease, biliary tract disease, and pancreatic disease. The drug will have a Risk Evaluation and Mitigation Strategy, consisting of a communication plan and training for prescribers, according to the FDA.

Pivotal data on the drug were published in September in Gastroenterology (Gastroenterology 2012 Sept. 13 [doi:10.1053/j.gastro.2012.09.007]).

The Food and Drug Administration on Dec. 21 approved teduglutide, to be marketed under the trade name Gattex, to treat adults with short bowel syndrome (SBS) who need parenteral nutrition.

Teduglutide, a recombinant analogue of human glucagon-like peptide-2 (GLP-2), was unanimously recommended for approval by an FDA advisory panel in October. It is a once-daily subcutaneous injection that helps improve intestinal absorption of fluids and nutrients, reducing the frequency and volume of parenteral nutrition.

"Considering Gattex has been shown to significantly reduce or in some cases even eliminate the requirement for parenteral support, it may become a cornerstone therapy in the management of short bowel syndrome." Dr. Ken Fujioka of the Nutrition and Metabolic Research Center, Scripps Clinic, Del Mar, Calif., said in a statement issued by Gattex’s maker, NPA Pharmaceuticals.

It is the third drug to be approved by the FDA for SBS patients who are dependent on parenteral nutrition. Somatropin (Zorbtive) was approved in 2003 and glutamine (Nutrestore) in 2004.

"Today’s approval expands the available treatment options for patients with this life-threatening condition," Dr. Victoria Kusiak, deputy director of the Office of Drug Evaluation III in the FDA Center for Drug Evaluation and Research, said in a statement. "Because Gattex may cause other serious health conditions, it is critical that patients and health care professionals understand the drug’s potential and known safety risks."

Teduglutide therapy increases the risk of developing cancer and polyps in the intestine, obstructions in the intestine, gallbladder disease, biliary tract disease, and pancreatic disease. The drug will have a Risk Evaluation and Mitigation Strategy, consisting of a communication plan and training for prescribers, according to the FDA.

Pivotal data on the drug were published in September in Gastroenterology (Gastroenterology 2012 Sept. 13 [doi:10.1053/j.gastro.2012.09.007]).

PALM BEACH, FLA.– Using laparoscopic surgery for colectomy with primary anastomosis in patients with complicated diverticulitis linked with significantly fewer major complications compared with open surgical management in a review of more than 10,000 patients from a nationwide database.

However, the inherent biases at play when surgeons decide whether to manage a diverticulitis patient by a laparoscopic or open approach make it difficult to draw definitive conclusions from the findings, Dr. Edward E. Cornwell III said at the annual meeting of the Southern Surgical Association.

"If a surgeon did an operation laparoscopically, that by itself is an indicator of how sick the patient was. The surgeon selects an open operation for sicker patients, and laparoscopy for the less sick patients," he said in an interview. "Have we accounted for that difference [in the analysis]? That’s an open question," said Dr. Cornwell, professor and chairman of surgery at Howard University in Washington.

"Patients whom the surgeon deem well enough physiologically to sustain colectomy with primary anastomosis deserve strong consideration for the laparoscopic approach because those patients had the greatest difference in complications" compared with open surgery, he said.

The data Dr. Cornwell and his associates reviewed also showed a marked skewing in how surgeons used laparoscopy. Among the 10,085 patients included in the analysis, 7,562 (75%) underwent colectomy with primary anastomosis, and in this subgroup, 5,105 patients (68%) had their surgery done laparoscopically, while the remaining 2,457 (32%) were done with open surgery. In contrast, the 2,523 other patients in the series underwent a colectomy with colostomy, and within this subgroup, 2,286 patients (91%) had open surgery, with only 237 (9%) having laparoscopic surgery.

The overwhelming use of open surgery for the colostomy patients makes sense as it is a more complex operation, Dr. Cornwell said.

He and his associates used data collected during 2005-2009 at 237 U.S. hospitals by the National Surgical Quality Improvement Program of the American College of Surgeons on patients who underwent surgical management of complicated diverticulitis. The average age of the patients was 58 years, and overall 30-day mortality was 2%, while the overall postoperative complication rate during the 30 days following surgery was 23%.

Among the patients who underwent a primary anastomosis, the incidence of major complications during 30 days of follow-up was 13% in the open surgery patients and 6% in the laparoscopy patients, a statistically significant difference. Major complications included surgical site infections, dehiscence, transfusion, respiratory failure, sepsis, myocardial infarction, pulmonary embolism, stroke, renal failure or need for rehospitalization.

In a multivariate analysis that controlled for demographic parameters, body mass index, comorbidities, and functional status, patients who underwent laparoscopy had about half the number of total complications and major complications compared with patients who underwent open surgery – statistically significant differences. The laparoscopically-treated patients also had roughly half the rate of several individual major complications – wound infections, respiratory complications, and sepsis – compared with the open surgery patients, all statistically significant differences.

Thirty-day mortality was about 50% lower with laparoscopy compared with open surgery among patients who underwent a primary anastomosis, but this difference fell short of statistical significance.

The advantage of laparoscopy over open surgery was not nearly so clear among patients who underwent colectomy with colostomy. The data showed no significant difference between laparoscopy and open surgery in the rate of all major complications, although the number of major complications with laparoscopy was about 20% lower. The only individual complications significantly reduced in the laparoscopy group were wound infections, reduced by about 40% in the adjusted analysis, and respiratory complications, cut by about 50% by laparoscopy. The two surgical subgroups showed virtually no difference in 30-day mortality among patients who underwent a colectomy.

The results suggest that because of the broad reduction of major complications with laparoscopy, this approach "should be considered when primary anastomosis is deemed appropriate," Dr. Cornwell concluded.

Dr. Cornwell said that he had no disclosures.

PALM BEACH, FLA.– Using laparoscopic surgery for colectomy with primary anastomosis in patients with complicated diverticulitis linked with significantly fewer major complications compared with open surgical management in a review of more than 10,000 patients from a nationwide database.

However, the inherent biases at play when surgeons decide whether to manage a diverticulitis patient by a laparoscopic or open approach make it difficult to draw definitive conclusions from the findings, Dr. Edward E. Cornwell III said at the annual meeting of the Southern Surgical Association.

"If a surgeon did an operation laparoscopically, that by itself is an indicator of how sick the patient was. The surgeon selects an open operation for sicker patients, and laparoscopy for the less sick patients," he said in an interview. "Have we accounted for that difference [in the analysis]? That’s an open question," said Dr. Cornwell, professor and chairman of surgery at Howard University in Washington.

"Patients whom the surgeon deem well enough physiologically to sustain colectomy with primary anastomosis deserve strong consideration for the laparoscopic approach because those patients had the greatest difference in complications" compared with open surgery, he said.

The data Dr. Cornwell and his associates reviewed also showed a marked skewing in how surgeons used laparoscopy. Among the 10,085 patients included in the analysis, 7,562 (75%) underwent colectomy with primary anastomosis, and in this subgroup, 5,105 patients (68%) had their surgery done laparoscopically, while the remaining 2,457 (32%) were done with open surgery. In contrast, the 2,523 other patients in the series underwent a colectomy with colostomy, and within this subgroup, 2,286 patients (91%) had open surgery, with only 237 (9%) having laparoscopic surgery.

The overwhelming use of open surgery for the colostomy patients makes sense as it is a more complex operation, Dr. Cornwell said.

He and his associates used data collected during 2005-2009 at 237 U.S. hospitals by the National Surgical Quality Improvement Program of the American College of Surgeons on patients who underwent surgical management of complicated diverticulitis. The average age of the patients was 58 years, and overall 30-day mortality was 2%, while the overall postoperative complication rate during the 30 days following surgery was 23%.

Among the patients who underwent a primary anastomosis, the incidence of major complications during 30 days of follow-up was 13% in the open surgery patients and 6% in the laparoscopy patients, a statistically significant difference. Major complications included surgical site infections, dehiscence, transfusion, respiratory failure, sepsis, myocardial infarction, pulmonary embolism, stroke, renal failure or need for rehospitalization.

In a multivariate analysis that controlled for demographic parameters, body mass index, comorbidities, and functional status, patients who underwent laparoscopy had about half the number of total complications and major complications compared with patients who underwent open surgery – statistically significant differences. The laparoscopically-treated patients also had roughly half the rate of several individual major complications – wound infections, respiratory complications, and sepsis – compared with the open surgery patients, all statistically significant differences.

Thirty-day mortality was about 50% lower with laparoscopy compared with open surgery among patients who underwent a primary anastomosis, but this difference fell short of statistical significance.

The advantage of laparoscopy over open surgery was not nearly so clear among patients who underwent colectomy with colostomy. The data showed no significant difference between laparoscopy and open surgery in the rate of all major complications, although the number of major complications with laparoscopy was about 20% lower. The only individual complications significantly reduced in the laparoscopy group were wound infections, reduced by about 40% in the adjusted analysis, and respiratory complications, cut by about 50% by laparoscopy. The two surgical subgroups showed virtually no difference in 30-day mortality among patients who underwent a colectomy.

The results suggest that because of the broad reduction of major complications with laparoscopy, this approach "should be considered when primary anastomosis is deemed appropriate," Dr. Cornwell concluded.

Dr. Cornwell said that he had no disclosures.

PALM BEACH, FLA.– Using laparoscopic surgery for colectomy with primary anastomosis in patients with complicated diverticulitis linked with significantly fewer major complications compared with open surgical management in a review of more than 10,000 patients from a nationwide database.

However, the inherent biases at play when surgeons decide whether to manage a diverticulitis patient by a laparoscopic or open approach make it difficult to draw definitive conclusions from the findings, Dr. Edward E. Cornwell III said at the annual meeting of the Southern Surgical Association.

"If a surgeon did an operation laparoscopically, that by itself is an indicator of how sick the patient was. The surgeon selects an open operation for sicker patients, and laparoscopy for the less sick patients," he said in an interview. "Have we accounted for that difference [in the analysis]? That’s an open question," said Dr. Cornwell, professor and chairman of surgery at Howard University in Washington.

"Patients whom the surgeon deem well enough physiologically to sustain colectomy with primary anastomosis deserve strong consideration for the laparoscopic approach because those patients had the greatest difference in complications" compared with open surgery, he said.

The data Dr. Cornwell and his associates reviewed also showed a marked skewing in how surgeons used laparoscopy. Among the 10,085 patients included in the analysis, 7,562 (75%) underwent colectomy with primary anastomosis, and in this subgroup, 5,105 patients (68%) had their surgery done laparoscopically, while the remaining 2,457 (32%) were done with open surgery. In contrast, the 2,523 other patients in the series underwent a colectomy with colostomy, and within this subgroup, 2,286 patients (91%) had open surgery, with only 237 (9%) having laparoscopic surgery.

The overwhelming use of open surgery for the colostomy patients makes sense as it is a more complex operation, Dr. Cornwell said.

He and his associates used data collected during 2005-2009 at 237 U.S. hospitals by the National Surgical Quality Improvement Program of the American College of Surgeons on patients who underwent surgical management of complicated diverticulitis. The average age of the patients was 58 years, and overall 30-day mortality was 2%, while the overall postoperative complication rate during the 30 days following surgery was 23%.

Among the patients who underwent a primary anastomosis, the incidence of major complications during 30 days of follow-up was 13% in the open surgery patients and 6% in the laparoscopy patients, a statistically significant difference. Major complications included surgical site infections, dehiscence, transfusion, respiratory failure, sepsis, myocardial infarction, pulmonary embolism, stroke, renal failure or need for rehospitalization.

In a multivariate analysis that controlled for demographic parameters, body mass index, comorbidities, and functional status, patients who underwent laparoscopy had about half the number of total complications and major complications compared with patients who underwent open surgery – statistically significant differences. The laparoscopically-treated patients also had roughly half the rate of several individual major complications – wound infections, respiratory complications, and sepsis – compared with the open surgery patients, all statistically significant differences.

Thirty-day mortality was about 50% lower with laparoscopy compared with open surgery among patients who underwent a primary anastomosis, but this difference fell short of statistical significance.

The advantage of laparoscopy over open surgery was not nearly so clear among patients who underwent colectomy with colostomy. The data showed no significant difference between laparoscopy and open surgery in the rate of all major complications, although the number of major complications with laparoscopy was about 20% lower. The only individual complications significantly reduced in the laparoscopy group were wound infections, reduced by about 40% in the adjusted analysis, and respiratory complications, cut by about 50% by laparoscopy. The two surgical subgroups showed virtually no difference in 30-day mortality among patients who underwent a colectomy.

The results suggest that because of the broad reduction of major complications with laparoscopy, this approach "should be considered when primary anastomosis is deemed appropriate," Dr. Cornwell concluded.

Dr. Cornwell said that he had no disclosures.