IBD & Intestinal Disorders

Treatment with the spores of nontoxigenic Clostridium difficile is well tolerated, and successful colonization of the gastrointestinal tract is associated with a significant reduction in C. difficile infection, according to a phase 2 study published May 5 in JAMA.

The randomized, double-blind, placebo-controlled study involving 173 patients with C. difficile infection showed that the lowest rate of recurrence (5%) was among the 43 patients who received the higher dose of 10⁷ spores/day for 7 days, compared with 15% recurrence in those who received 10⁷ spores/day for 14 days or 10⁴ spores/day for 7 days, and 30% in the placebo group, reported Dr. Dale N. Gerding of Edward Hines, Jr. VA Hospital, Hines, Ill. and his associates.

Courtesy Loyola University Health System

The multicenter study, which involved patients who had all successfully completed treatment with metronidazole, oral vancomycin, or both, showed that fecal colonization occurred in 71% of patients who received the higher spore dose for 7 days and 63% of those who received the lower dose (JAMA 2015;313:1719-27 [doi:10.1001/jama.2015.3725]).

“The most likely hypothesized mechanism of action of NTCD-M3 [nontoxigenic C. difficile strain M3] is that it occupies the same metabolic or adherence niche in the gastrointestinal tract as does toxigenic C. difficile and, once established, is able to outcompete resident or newly ingested toxigenic strains,” Dr. Gerding and his associates wrote.

The study was sponsored by ViroPharma Incorporated. One author declared patents for the prevention of C. difficile infection, licensed to ViroPharma/Shire, and two authors were employees of ViroPharma/Shire during the study. Other authors reported personal fees, board positions, clinical trial participation, and consultancies with pharmaceutical companies, including the study sponsor.

Treatment with the spores of nontoxigenic Clostridium difficile is well tolerated, and successful colonization of the gastrointestinal tract is associated with a significant reduction in C. difficile infection, according to a phase 2 study published May 5 in JAMA.

The randomized, double-blind, placebo-controlled study involving 173 patients with C. difficile infection showed that the lowest rate of recurrence (5%) was among the 43 patients who received the higher dose of 10⁷ spores/day for 7 days, compared with 15% recurrence in those who received 10⁷ spores/day for 14 days or 10⁴ spores/day for 7 days, and 30% in the placebo group, reported Dr. Dale N. Gerding of Edward Hines, Jr. VA Hospital, Hines, Ill. and his associates.

Courtesy Loyola University Health System

The multicenter study, which involved patients who had all successfully completed treatment with metronidazole, oral vancomycin, or both, showed that fecal colonization occurred in 71% of patients who received the higher spore dose for 7 days and 63% of those who received the lower dose (JAMA 2015;313:1719-27 [doi:10.1001/jama.2015.3725]).

“The most likely hypothesized mechanism of action of NTCD-M3 [nontoxigenic C. difficile strain M3] is that it occupies the same metabolic or adherence niche in the gastrointestinal tract as does toxigenic C. difficile and, once established, is able to outcompete resident or newly ingested toxigenic strains,” Dr. Gerding and his associates wrote.

The study was sponsored by ViroPharma Incorporated. One author declared patents for the prevention of C. difficile infection, licensed to ViroPharma/Shire, and two authors were employees of ViroPharma/Shire during the study. Other authors reported personal fees, board positions, clinical trial participation, and consultancies with pharmaceutical companies, including the study sponsor.

Treatment with the spores of nontoxigenic Clostridium difficile is well tolerated, and successful colonization of the gastrointestinal tract is associated with a significant reduction in C. difficile infection, according to a phase 2 study published May 5 in JAMA.

The randomized, double-blind, placebo-controlled study involving 173 patients with C. difficile infection showed that the lowest rate of recurrence (5%) was among the 43 patients who received the higher dose of 10⁷ spores/day for 7 days, compared with 15% recurrence in those who received 10⁷ spores/day for 14 days or 10⁴ spores/day for 7 days, and 30% in the placebo group, reported Dr. Dale N. Gerding of Edward Hines, Jr. VA Hospital, Hines, Ill. and his associates.

Courtesy Loyola University Health System

The multicenter study, which involved patients who had all successfully completed treatment with metronidazole, oral vancomycin, or both, showed that fecal colonization occurred in 71% of patients who received the higher spore dose for 7 days and 63% of those who received the lower dose (JAMA 2015;313:1719-27 [doi:10.1001/jama.2015.3725]).

“The most likely hypothesized mechanism of action of NTCD-M3 [nontoxigenic C. difficile strain M3] is that it occupies the same metabolic or adherence niche in the gastrointestinal tract as does toxigenic C. difficile and, once established, is able to outcompete resident or newly ingested toxigenic strains,” Dr. Gerding and his associates wrote.

The study was sponsored by ViroPharma Incorporated. One author declared patents for the prevention of C. difficile infection, licensed to ViroPharma/Shire, and two authors were employees of ViroPharma/Shire during the study. Other authors reported personal fees, board positions, clinical trial participation, and consultancies with pharmaceutical companies, including the study sponsor.

SAN DIEGO – Unlike in adults, inpatient administration of “high-risk” antibiotics such as cephalosporins, clindamycin, and aminopenicillins are not risk factors for recurrent Clostridium difficile infection in children, results from a multicenter study demonstrated.

“There are previous studies in which recurrent Clostridium difficile infection risk prediction models have been compiled for adult hospitalized patients,” lead study author Anthony Goudie, Ph.D., said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “Our work is the first known risk prediction model specifically looking at the pediatric population.”

Dr. Goudie of the Center for Applied Research and Evaluation in the department of pediatrics at the University of Arkansas for Medical Sciences, Little Rock, said that an adult risk prediction model (J. Hosp. Med. 2014;9:418-23) for recurrent Clostridium difficile infection (rCDI) found no association between clinical diagnoses during hospitalization for the incident CDI (iCDI). However, the model did find a strong positive association between rCDI and increasing patient age, number of recent prior hospitalizations, and the administration of gastric acid suppressors, high-risk antibiotics, or fluoroquinolones during the iCDI hospitalization.

To test the validity of adult rCDI risk factors in a pediatric population, Dr. Goudie and his associates conducted a secondary analysis of data from 43 children’s hospitals in the United States reporting to the Pediatric Health Information System between 2009 and 2013. They defined iCDI by the discharge ICD-9 code 00.845 and the administration of metronidazole or oral vancomycin during the hospital stay, and they defined rCDI as readmission with CDI within 42 days of the end of iCDI treatment. Next, the researchers statistically modeled all cases of iCDI for rCDI and tested for predictors among several factors including age, race/ethnicity, insurance status, use of antibiotics including cephalosporins, clindamycin, and aminopenicillins, and all of the predictors associated with rCDI in the adult risk prediction model.

Of 7,798 iCDI cases reported during the study period, 567 (7.3%), experienced a subsequent rCDI. No association between rCDI was seen among children who were administered histamine-2 receptor blocker (H2RB) gastric acid suppressors (P = .81), or any of all generations of cephalosporins, clindamycin, aminopenicillins, aminoglycosides, carbapenems, and fluoroquinolone antibiotics (all P greater than .10). A positive association (P less than .05) was seen among children 1-3 years, those covered by Medicaid insurance, those who had community-acquired iCDI, those who had a prior hospitalization, those administered tetracycline antibiotics, and those who were administered proton pump inhibitors.

In addition, rCDI was significantly associated with a number of iCDI comorbid diagnoses, including Hodgkin’s disease; non-Hodgkin’s lymphoma; spondylosis, intervertebral disk disorders, or other back problems; cancer of bone or connective tissue; cancer of the brain or nervous system; maintenance chemotherapy and radiotherapy; and leukemia (P less than .05 for all).

“Of all of our results, we were especially surprised to find that compared to children covered by private health insurance, those covered by Medicaid had higher odds of having rCDI,” Dr. Goudie said. “While more study is needed, we think that Medicaid in this context may be a proxy for socioeconomic status and at least a part of the solution to reducing rCDI may lie outside the control of hospital-based quality improvement interventions.”

He acknowledged certain limitations of study, including the fact the researchers “have no clinical data on children who may have been seen at other hospitals before or after the incident or rCDI [was] identified at the children’s hospital.”

The researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN DIEGO – Unlike in adults, inpatient administration of “high-risk” antibiotics such as cephalosporins, clindamycin, and aminopenicillins are not risk factors for recurrent Clostridium difficile infection in children, results from a multicenter study demonstrated.

“There are previous studies in which recurrent Clostridium difficile infection risk prediction models have been compiled for adult hospitalized patients,” lead study author Anthony Goudie, Ph.D., said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “Our work is the first known risk prediction model specifically looking at the pediatric population.”

Dr. Goudie of the Center for Applied Research and Evaluation in the department of pediatrics at the University of Arkansas for Medical Sciences, Little Rock, said that an adult risk prediction model (J. Hosp. Med. 2014;9:418-23) for recurrent Clostridium difficile infection (rCDI) found no association between clinical diagnoses during hospitalization for the incident CDI (iCDI). However, the model did find a strong positive association between rCDI and increasing patient age, number of recent prior hospitalizations, and the administration of gastric acid suppressors, high-risk antibiotics, or fluoroquinolones during the iCDI hospitalization.

To test the validity of adult rCDI risk factors in a pediatric population, Dr. Goudie and his associates conducted a secondary analysis of data from 43 children’s hospitals in the United States reporting to the Pediatric Health Information System between 2009 and 2013. They defined iCDI by the discharge ICD-9 code 00.845 and the administration of metronidazole or oral vancomycin during the hospital stay, and they defined rCDI as readmission with CDI within 42 days of the end of iCDI treatment. Next, the researchers statistically modeled all cases of iCDI for rCDI and tested for predictors among several factors including age, race/ethnicity, insurance status, use of antibiotics including cephalosporins, clindamycin, and aminopenicillins, and all of the predictors associated with rCDI in the adult risk prediction model.

Of 7,798 iCDI cases reported during the study period, 567 (7.3%), experienced a subsequent rCDI. No association between rCDI was seen among children who were administered histamine-2 receptor blocker (H2RB) gastric acid suppressors (P = .81), or any of all generations of cephalosporins, clindamycin, aminopenicillins, aminoglycosides, carbapenems, and fluoroquinolone antibiotics (all P greater than .10). A positive association (P less than .05) was seen among children 1-3 years, those covered by Medicaid insurance, those who had community-acquired iCDI, those who had a prior hospitalization, those administered tetracycline antibiotics, and those who were administered proton pump inhibitors.

In addition, rCDI was significantly associated with a number of iCDI comorbid diagnoses, including Hodgkin’s disease; non-Hodgkin’s lymphoma; spondylosis, intervertebral disk disorders, or other back problems; cancer of bone or connective tissue; cancer of the brain or nervous system; maintenance chemotherapy and radiotherapy; and leukemia (P less than .05 for all).

“Of all of our results, we were especially surprised to find that compared to children covered by private health insurance, those covered by Medicaid had higher odds of having rCDI,” Dr. Goudie said. “While more study is needed, we think that Medicaid in this context may be a proxy for socioeconomic status and at least a part of the solution to reducing rCDI may lie outside the control of hospital-based quality improvement interventions.”

He acknowledged certain limitations of study, including the fact the researchers “have no clinical data on children who may have been seen at other hospitals before or after the incident or rCDI [was] identified at the children’s hospital.”

The researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN DIEGO – Unlike in adults, inpatient administration of “high-risk” antibiotics such as cephalosporins, clindamycin, and aminopenicillins are not risk factors for recurrent Clostridium difficile infection in children, results from a multicenter study demonstrated.

“There are previous studies in which recurrent Clostridium difficile infection risk prediction models have been compiled for adult hospitalized patients,” lead study author Anthony Goudie, Ph.D., said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “Our work is the first known risk prediction model specifically looking at the pediatric population.”

Dr. Goudie of the Center for Applied Research and Evaluation in the department of pediatrics at the University of Arkansas for Medical Sciences, Little Rock, said that an adult risk prediction model (J. Hosp. Med. 2014;9:418-23) for recurrent Clostridium difficile infection (rCDI) found no association between clinical diagnoses during hospitalization for the incident CDI (iCDI). However, the model did find a strong positive association between rCDI and increasing patient age, number of recent prior hospitalizations, and the administration of gastric acid suppressors, high-risk antibiotics, or fluoroquinolones during the iCDI hospitalization.

To test the validity of adult rCDI risk factors in a pediatric population, Dr. Goudie and his associates conducted a secondary analysis of data from 43 children’s hospitals in the United States reporting to the Pediatric Health Information System between 2009 and 2013. They defined iCDI by the discharge ICD-9 code 00.845 and the administration of metronidazole or oral vancomycin during the hospital stay, and they defined rCDI as readmission with CDI within 42 days of the end of iCDI treatment. Next, the researchers statistically modeled all cases of iCDI for rCDI and tested for predictors among several factors including age, race/ethnicity, insurance status, use of antibiotics including cephalosporins, clindamycin, and aminopenicillins, and all of the predictors associated with rCDI in the adult risk prediction model.

Of 7,798 iCDI cases reported during the study period, 567 (7.3%), experienced a subsequent rCDI. No association between rCDI was seen among children who were administered histamine-2 receptor blocker (H2RB) gastric acid suppressors (P = .81), or any of all generations of cephalosporins, clindamycin, aminopenicillins, aminoglycosides, carbapenems, and fluoroquinolone antibiotics (all P greater than .10). A positive association (P less than .05) was seen among children 1-3 years, those covered by Medicaid insurance, those who had community-acquired iCDI, those who had a prior hospitalization, those administered tetracycline antibiotics, and those who were administered proton pump inhibitors.

In addition, rCDI was significantly associated with a number of iCDI comorbid diagnoses, including Hodgkin’s disease; non-Hodgkin’s lymphoma; spondylosis, intervertebral disk disorders, or other back problems; cancer of bone or connective tissue; cancer of the brain or nervous system; maintenance chemotherapy and radiotherapy; and leukemia (P less than .05 for all).

“Of all of our results, we were especially surprised to find that compared to children covered by private health insurance, those covered by Medicaid had higher odds of having rCDI,” Dr. Goudie said. “While more study is needed, we think that Medicaid in this context may be a proxy for socioeconomic status and at least a part of the solution to reducing rCDI may lie outside the control of hospital-based quality improvement interventions.”

He acknowledged certain limitations of study, including the fact the researchers “have no clinical data on children who may have been seen at other hospitals before or after the incident or rCDI [was] identified at the children’s hospital.”

The researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

Three-quarters of Crohn’s fistula patients who were treated with one or two doses of autologous mesenchymal stem cells derived from adipose tissue achieved complete closure at 2 years of follow-up, a retrospective analysis showed.

“Crohn’s fistula is one of the most distressing diseases because it decreases patient’s quality of life and frequently recurs,” South Korean researchers led by Dr. Yong Beom Cho wrote in a study published online March 31, 2015, in Stem Cells Translational Medicine. “It has been reported to occur in 13%-38% of patients with Crohn’s disease and a proctectomy is required in 10%-18% of Crohn’s patients over the course of the disease.” To date, they continued, treatment with antibiotics and biological agents remain unsatisfactory “because they fail to achieve complete closure, lower recurrence, and limit adverse effects.”

Over the past several years, researchers have been evaluating the efficacy of stem cell therapy for treating Crohn’s fistula, including those derived from bone marrow and adipose tissue. An earlier phase II trial conducted by Dr. Cho of the department of surgery at Samsung Medical Center, Seoul, South Korea, and associates found that using mesenchymal stem cells derived from adipose tissue (ASCs) resulted in favorable efficacy and complete healing in 82% of 43 patients at 1 year (Stem Cells Trans. Med. 2013;31:2575-81). The purpose of the current trial was to evaluate the outcome of this approach by following the patients for an additional year.

For the current phase II trial, the researchers followed 41 of the 43 patients from the initial trial, which took place at five hospitals in South Korea from January 2010 to August 2012 and involved one or two injections of ASCs into the tract of fistulae associated with Crohn’s disease (Stem Cells Trans. Med. 2015 March 31 [doi:10.5966/sctm.2014-0199]). At baseline the mean age of patients was 26 years, 68% were male, the mean fistula length was 4.6 cm, and the average duration of Crohn’s disease was 58 months. Modified intention-to-treat (mITT) and modified per protocol (mPP) analysis were used to assess efficacy. Patients who received other surgical procedures or operations involving the injection site were excluded from the mPP analysis, while the mITT analysis included patients who received ASC treatment and had efficacy data at month 24.

At 24 months, complete fistula healing was observed in 81% of patients in the mPP analysis and 75% of patients in the mITT analysis. Furthermore, 83% of patients who showed complete closure at week 8 after ASC injection still showed complete closure at 24 months. No adverse events related to the administration of ASCs were observed.

“ASCs represent a novel therapeutic option for Crohn’s fistulae with a high risk of recurrence, showing durable efficacy with low recurrence, even in cases in which healing cannot be achieved with biologics or in which conventional surgical procedures cannot be performed,” the researchers concluded. “Such refractory patients should be referred to tertiary centers where optimal therapy, including stem cell implants, can be offered.”

The work was supported by the National Institutes of Health Clinical Trials. Two of the study authors are employees of Anterogen Co. The remaining researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

Three-quarters of Crohn’s fistula patients who were treated with one or two doses of autologous mesenchymal stem cells derived from adipose tissue achieved complete closure at 2 years of follow-up, a retrospective analysis showed.

“Crohn’s fistula is one of the most distressing diseases because it decreases patient’s quality of life and frequently recurs,” South Korean researchers led by Dr. Yong Beom Cho wrote in a study published online March 31, 2015, in Stem Cells Translational Medicine. “It has been reported to occur in 13%-38% of patients with Crohn’s disease and a proctectomy is required in 10%-18% of Crohn’s patients over the course of the disease.” To date, they continued, treatment with antibiotics and biological agents remain unsatisfactory “because they fail to achieve complete closure, lower recurrence, and limit adverse effects.”

Over the past several years, researchers have been evaluating the efficacy of stem cell therapy for treating Crohn’s fistula, including those derived from bone marrow and adipose tissue. An earlier phase II trial conducted by Dr. Cho of the department of surgery at Samsung Medical Center, Seoul, South Korea, and associates found that using mesenchymal stem cells derived from adipose tissue (ASCs) resulted in favorable efficacy and complete healing in 82% of 43 patients at 1 year (Stem Cells Trans. Med. 2013;31:2575-81). The purpose of the current trial was to evaluate the outcome of this approach by following the patients for an additional year.

For the current phase II trial, the researchers followed 41 of the 43 patients from the initial trial, which took place at five hospitals in South Korea from January 2010 to August 2012 and involved one or two injections of ASCs into the tract of fistulae associated with Crohn’s disease (Stem Cells Trans. Med. 2015 March 31 [doi:10.5966/sctm.2014-0199]). At baseline the mean age of patients was 26 years, 68% were male, the mean fistula length was 4.6 cm, and the average duration of Crohn’s disease was 58 months. Modified intention-to-treat (mITT) and modified per protocol (mPP) analysis were used to assess efficacy. Patients who received other surgical procedures or operations involving the injection site were excluded from the mPP analysis, while the mITT analysis included patients who received ASC treatment and had efficacy data at month 24.

At 24 months, complete fistula healing was observed in 81% of patients in the mPP analysis and 75% of patients in the mITT analysis. Furthermore, 83% of patients who showed complete closure at week 8 after ASC injection still showed complete closure at 24 months. No adverse events related to the administration of ASCs were observed.

“ASCs represent a novel therapeutic option for Crohn’s fistulae with a high risk of recurrence, showing durable efficacy with low recurrence, even in cases in which healing cannot be achieved with biologics or in which conventional surgical procedures cannot be performed,” the researchers concluded. “Such refractory patients should be referred to tertiary centers where optimal therapy, including stem cell implants, can be offered.”

The work was supported by the National Institutes of Health Clinical Trials. Two of the study authors are employees of Anterogen Co. The remaining researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

Three-quarters of Crohn’s fistula patients who were treated with one or two doses of autologous mesenchymal stem cells derived from adipose tissue achieved complete closure at 2 years of follow-up, a retrospective analysis showed.

“Crohn’s fistula is one of the most distressing diseases because it decreases patient’s quality of life and frequently recurs,” South Korean researchers led by Dr. Yong Beom Cho wrote in a study published online March 31, 2015, in Stem Cells Translational Medicine. “It has been reported to occur in 13%-38% of patients with Crohn’s disease and a proctectomy is required in 10%-18% of Crohn’s patients over the course of the disease.” To date, they continued, treatment with antibiotics and biological agents remain unsatisfactory “because they fail to achieve complete closure, lower recurrence, and limit adverse effects.”

Over the past several years, researchers have been evaluating the efficacy of stem cell therapy for treating Crohn’s fistula, including those derived from bone marrow and adipose tissue. An earlier phase II trial conducted by Dr. Cho of the department of surgery at Samsung Medical Center, Seoul, South Korea, and associates found that using mesenchymal stem cells derived from adipose tissue (ASCs) resulted in favorable efficacy and complete healing in 82% of 43 patients at 1 year (Stem Cells Trans. Med. 2013;31:2575-81). The purpose of the current trial was to evaluate the outcome of this approach by following the patients for an additional year.

For the current phase II trial, the researchers followed 41 of the 43 patients from the initial trial, which took place at five hospitals in South Korea from January 2010 to August 2012 and involved one or two injections of ASCs into the tract of fistulae associated with Crohn’s disease (Stem Cells Trans. Med. 2015 March 31 [doi:10.5966/sctm.2014-0199]). At baseline the mean age of patients was 26 years, 68% were male, the mean fistula length was 4.6 cm, and the average duration of Crohn’s disease was 58 months. Modified intention-to-treat (mITT) and modified per protocol (mPP) analysis were used to assess efficacy. Patients who received other surgical procedures or operations involving the injection site were excluded from the mPP analysis, while the mITT analysis included patients who received ASC treatment and had efficacy data at month 24.

At 24 months, complete fistula healing was observed in 81% of patients in the mPP analysis and 75% of patients in the mITT analysis. Furthermore, 83% of patients who showed complete closure at week 8 after ASC injection still showed complete closure at 24 months. No adverse events related to the administration of ASCs were observed.

“ASCs represent a novel therapeutic option for Crohn’s fistulae with a high risk of recurrence, showing durable efficacy with low recurrence, even in cases in which healing cannot be achieved with biologics or in which conventional surgical procedures cannot be performed,” the researchers concluded. “Such refractory patients should be referred to tertiary centers where optimal therapy, including stem cell implants, can be offered.”

The work was supported by the National Institutes of Health Clinical Trials. Two of the study authors are employees of Anterogen Co. The remaining researchers reported having no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – Colonoscopy may be the most commonly used technique to screen for colorectal cancer in the United States, but it’s far from perfect, according to Dr. David A. Lieberman.

For one thing, serious complications occur in 3-5 per 1,000 procedures at 30 days of follow-up, “and if you look at individuals over 65, the rates almost double in terms of serious complications,” Dr. Lieberman, chief of the division of gastroenterology and hepatology at Oregon Health and Science University, said at the 2015 AGA Tech Summit, which is sponsored by the AGA Center for GI Innovation and Technology. “The rate of perforation over age 65 is about 1 per 1,000,” he said.

Colonoscopy is invasive, “and it would never be conceived of as the ideal test for population-based screening,” he added. “It’s expensive, and [clinicians] in many countries simply do not have the resources and expertise to do it.”

Compared with current screening rates in the United States for cervical and breast cancer, a “screening gap” exists in the percentage of adults who are up to date in tests for colorectal cancer, he said. “If you look at what’s been accomplished with cervical cancer screening and mammography, we see that there’s a ways to go for colonoscopy,” he said.

The ideal screening test for colorectal cancer would accurately identify individuals at risk for colon cancer at an early, preventable stage, Dr. Lieberman said. That prevention element “really averts the downstream colon cancer care costs, which would be very attractive in a single-payer health care system,” he said. “If we had a system that took care of us for life, that system would be very invested in trying to prevent colon cancer, because [it would] be worried about those downstream costs.”

One potential alternative to colonoscopy is fecal immunochemical testing (FIT). A recent meta-analysis suggested that FIT detected cancer with a 79% sensitivity (Ann. Intern. Med. 2014;160:171-81), and a separate, recent prospective study found a 74% sensitivity rate in detecting cancer, but a 24% sensitivity rate in detecting advanced adenoma (N. Engl. J. Med. 2014;370:1287-97). “So in terms of early detection, FIT is pretty good,” Dr. Lieberman said. “In terms of cancer prevention? Maybe not so good. There are also issues around the testing program, which requires adherence to both positive and negative tests. Some of these behavioral factors play a major role in the actual effectiveness. So you can have a great test, but if it’s not getting done properly then there’s going to be an issue. There is some potential for CRC prevention, but it’s going to be less than for some others.”

What about stool DNA? A landmark study found that stool DNA detected cancer with a sensitivity of 92%, compared with FIT at 74% (N. Engl. J Med. 2014;370:1287-97). However, the sensitivity for detecting adenomas was relatively low for both methods (42% for stool DNA, compared with 24% for FIT). Stool DNA testing “appears to be an effective screening test [but] the appropriate interval for testing is still uncertain,” Dr. Lieberman said. “The recommendation is a 3-year interval.”

He characterized serum testing as the “holy grail” of screening for colorectal cancer, “because it would be ideal to have a noninvasive test. You’d come in, get a blood draw, and get risk stratified. There are a number of different possible pathways, one looking at specific genetic markers, others looking at genetic fingerprinting: in other words, seeing a pattern of genes that are associated with colon cancer versus patients who do not have colon cancer. Proteomics is another fingerprinting technique, as is metabolomics: looking at a variety of metabolites that may be altered by the presence of having neoplasia. This is an intriguing area but so far there hasn’t been a lot of data.”

To date, the most progress involved in this area involves molecular tests of DNA or proteins. “These studies are all relatively small and somewhat promising in terms of cancer sensitivity, but not so great for adenoma sensitivity,” he said. “It’s fair to say that this is still a work in progress.”

Dr. Lieberman reported having served on the scientific advisory board of Exact Sciences.

In a separate presentation, Dr. Uri Ladabaum updated attendees on the status of PillCam, also known as colon capsule endoscopy (CCE), for detecting colon cancer. The PillCam is cleared by the Food and Drug Administration for detection of colon polyps in patients after an incomplete optical colonoscopy with adequate preparation, or if a complete evaluation of the colon was not technically possible. In a large meta-analysis, the first-generation PillCam achieved a sensitivity of 71% and a specificity of 75% in detecting polyps of any size and a sensitivity of 68% and a specificity of 82% in detecting polyps 6 mm in size or larger (Clin. Gastroenterol. Hepatol. 2010;8:515-22). “The results were somewhat disappointing for a test like this, not hitting the bar that we would want,” said Dr. Ladabaum, professor of medicine in the division of gastroenterology and hepatology at Stanford (Calif.) University.

The second generation PillCam features an improved angle of the imagers, from 156 degrees to 172 degrees, “so you get a bigger view all the way around,” he said. Another new feature is an adaptive imaging rate. The first-generation device captured 4 images per second regardless of where the capsule was moving. The new system “goes at 4 images per second when stationary, goes as fast as 35 imagers per second while moving, and 14 images per second before it reaches the small bowel,” Dr. Ladabaum said.

In an early study of the second-generation system, the device achieved a sensitivity of 89% and a specificity of 76% in detecting polyps of 6 mm in size or larger and a sensitivity of 88% and a specificity of 89% in detecting polyps 10 mm in size or larger (Endoscopy 2009;41:1026-31).

More recently, researchers examined consecutive patients who had incomplete colonoscopy and compared a follow-up with either second-generation CCE or CT colonography (Gut 2015;64:272-81). The diagnostic yield of CCE and CT colonography was 25% and 12%, respectively, for polyps 6 mm or larger and 5% vs. 3% for polyps 10 mm or larger.

In a larger, multisite study, researchers examined the efficacy of the second-generation PillCam as a primary screening tool (Gastroenterology 2015 [doi:10.1053/j.gastro.2015.01.025). Of 884 subjects enrolled, 85 were excluded from the analysis for a variety of reasons. Of these, 12 were excluded because the capsule did not reach the colon within 12 hours and 8 were excluded because the capsule did not pass the cecum within 12 hours. “So if used in practice, we’ll see this – [incomplete capsule studies],” Dr. Ladabaum said.

In addition, 77 were excluded for inadequate cleansing and capsule transit time through the colon in less than 40 minutes. “Maybe that’s due to the booster regimen,” he said. “There are still some things to work out in the bowel prep. Overall, there were a good number of people [in this study] who didn’t really have the exam [completed as intended]. Is that going to pan out as a big problem in clinical practice? That remains to be seen.”

The study found that the second-generation PillCam achieved a sensitivity of 87% and a specificity of 94% in detecting polyps 6 mm or larger and a sensitivity of 85% and a specificity of 97% in detecting polyps 10 mm in size or larger. “Is this good enough for this kind of technology?” Dr. Ladabaum asked. “There’s lots of room for debate here. Interestingly, the numbers for sessile serrated polyps didn’t look that good” (a sensitivity of 29% for polyps 6 mm in size or greater and 33% for polyps 10 mm in size or greater).

Dr. Ladabaum disclosed that he has served as a consultant for Given Imaging and Exact Sciences. He has also served on the advisory board for Mauna Kea Technologies.

In conclusion, according to Dr. Lieberman, there are several feasible alternatives to colonoscopy for primary colon cancer screening in average-risk individuals. Each has advantages and limitations and offers a less invasive approach to screening. The bar for screening has been raised from early cancer detection alone to both early detection and prevention. These less invasive tests will be expected to achieve accurate detection of individuals with early stage colon cancer and those at risk for colon cancer.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Colonoscopy may be the most commonly used technique to screen for colorectal cancer in the United States, but it’s far from perfect, according to Dr. David A. Lieberman.

For one thing, serious complications occur in 3-5 per 1,000 procedures at 30 days of follow-up, “and if you look at individuals over 65, the rates almost double in terms of serious complications,” Dr. Lieberman, chief of the division of gastroenterology and hepatology at Oregon Health and Science University, said at the 2015 AGA Tech Summit, which is sponsored by the AGA Center for GI Innovation and Technology. “The rate of perforation over age 65 is about 1 per 1,000,” he said.

Colonoscopy is invasive, “and it would never be conceived of as the ideal test for population-based screening,” he added. “It’s expensive, and [clinicians] in many countries simply do not have the resources and expertise to do it.”

Compared with current screening rates in the United States for cervical and breast cancer, a “screening gap” exists in the percentage of adults who are up to date in tests for colorectal cancer, he said. “If you look at what’s been accomplished with cervical cancer screening and mammography, we see that there’s a ways to go for colonoscopy,” he said.

The ideal screening test for colorectal cancer would accurately identify individuals at risk for colon cancer at an early, preventable stage, Dr. Lieberman said. That prevention element “really averts the downstream colon cancer care costs, which would be very attractive in a single-payer health care system,” he said. “If we had a system that took care of us for life, that system would be very invested in trying to prevent colon cancer, because [it would] be worried about those downstream costs.”

One potential alternative to colonoscopy is fecal immunochemical testing (FIT). A recent meta-analysis suggested that FIT detected cancer with a 79% sensitivity (Ann. Intern. Med. 2014;160:171-81), and a separate, recent prospective study found a 74% sensitivity rate in detecting cancer, but a 24% sensitivity rate in detecting advanced adenoma (N. Engl. J. Med. 2014;370:1287-97). “So in terms of early detection, FIT is pretty good,” Dr. Lieberman said. “In terms of cancer prevention? Maybe not so good. There are also issues around the testing program, which requires adherence to both positive and negative tests. Some of these behavioral factors play a major role in the actual effectiveness. So you can have a great test, but if it’s not getting done properly then there’s going to be an issue. There is some potential for CRC prevention, but it’s going to be less than for some others.”

What about stool DNA? A landmark study found that stool DNA detected cancer with a sensitivity of 92%, compared with FIT at 74% (N. Engl. J Med. 2014;370:1287-97). However, the sensitivity for detecting adenomas was relatively low for both methods (42% for stool DNA, compared with 24% for FIT). Stool DNA testing “appears to be an effective screening test [but] the appropriate interval for testing is still uncertain,” Dr. Lieberman said. “The recommendation is a 3-year interval.”

He characterized serum testing as the “holy grail” of screening for colorectal cancer, “because it would be ideal to have a noninvasive test. You’d come in, get a blood draw, and get risk stratified. There are a number of different possible pathways, one looking at specific genetic markers, others looking at genetic fingerprinting: in other words, seeing a pattern of genes that are associated with colon cancer versus patients who do not have colon cancer. Proteomics is another fingerprinting technique, as is metabolomics: looking at a variety of metabolites that may be altered by the presence of having neoplasia. This is an intriguing area but so far there hasn’t been a lot of data.”

To date, the most progress involved in this area involves molecular tests of DNA or proteins. “These studies are all relatively small and somewhat promising in terms of cancer sensitivity, but not so great for adenoma sensitivity,” he said. “It’s fair to say that this is still a work in progress.”

Dr. Lieberman reported having served on the scientific advisory board of Exact Sciences.

In a separate presentation, Dr. Uri Ladabaum updated attendees on the status of PillCam, also known as colon capsule endoscopy (CCE), for detecting colon cancer. The PillCam is cleared by the Food and Drug Administration for detection of colon polyps in patients after an incomplete optical colonoscopy with adequate preparation, or if a complete evaluation of the colon was not technically possible. In a large meta-analysis, the first-generation PillCam achieved a sensitivity of 71% and a specificity of 75% in detecting polyps of any size and a sensitivity of 68% and a specificity of 82% in detecting polyps 6 mm in size or larger (Clin. Gastroenterol. Hepatol. 2010;8:515-22). “The results were somewhat disappointing for a test like this, not hitting the bar that we would want,” said Dr. Ladabaum, professor of medicine in the division of gastroenterology and hepatology at Stanford (Calif.) University.

The second generation PillCam features an improved angle of the imagers, from 156 degrees to 172 degrees, “so you get a bigger view all the way around,” he said. Another new feature is an adaptive imaging rate. The first-generation device captured 4 images per second regardless of where the capsule was moving. The new system “goes at 4 images per second when stationary, goes as fast as 35 imagers per second while moving, and 14 images per second before it reaches the small bowel,” Dr. Ladabaum said.

In an early study of the second-generation system, the device achieved a sensitivity of 89% and a specificity of 76% in detecting polyps of 6 mm in size or larger and a sensitivity of 88% and a specificity of 89% in detecting polyps 10 mm in size or larger (Endoscopy 2009;41:1026-31).

More recently, researchers examined consecutive patients who had incomplete colonoscopy and compared a follow-up with either second-generation CCE or CT colonography (Gut 2015;64:272-81). The diagnostic yield of CCE and CT colonography was 25% and 12%, respectively, for polyps 6 mm or larger and 5% vs. 3% for polyps 10 mm or larger.

In a larger, multisite study, researchers examined the efficacy of the second-generation PillCam as a primary screening tool (Gastroenterology 2015 [doi:10.1053/j.gastro.2015.01.025). Of 884 subjects enrolled, 85 were excluded from the analysis for a variety of reasons. Of these, 12 were excluded because the capsule did not reach the colon within 12 hours and 8 were excluded because the capsule did not pass the cecum within 12 hours. “So if used in practice, we’ll see this – [incomplete capsule studies],” Dr. Ladabaum said.

In addition, 77 were excluded for inadequate cleansing and capsule transit time through the colon in less than 40 minutes. “Maybe that’s due to the booster regimen,” he said. “There are still some things to work out in the bowel prep. Overall, there were a good number of people [in this study] who didn’t really have the exam [completed as intended]. Is that going to pan out as a big problem in clinical practice? That remains to be seen.”

The study found that the second-generation PillCam achieved a sensitivity of 87% and a specificity of 94% in detecting polyps 6 mm or larger and a sensitivity of 85% and a specificity of 97% in detecting polyps 10 mm in size or larger. “Is this good enough for this kind of technology?” Dr. Ladabaum asked. “There’s lots of room for debate here. Interestingly, the numbers for sessile serrated polyps didn’t look that good” (a sensitivity of 29% for polyps 6 mm in size or greater and 33% for polyps 10 mm in size or greater).

Dr. Ladabaum disclosed that he has served as a consultant for Given Imaging and Exact Sciences. He has also served on the advisory board for Mauna Kea Technologies.

In conclusion, according to Dr. Lieberman, there are several feasible alternatives to colonoscopy for primary colon cancer screening in average-risk individuals. Each has advantages and limitations and offers a less invasive approach to screening. The bar for screening has been raised from early cancer detection alone to both early detection and prevention. These less invasive tests will be expected to achieve accurate detection of individuals with early stage colon cancer and those at risk for colon cancer.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Colonoscopy may be the most commonly used technique to screen for colorectal cancer in the United States, but it’s far from perfect, according to Dr. David A. Lieberman.

For one thing, serious complications occur in 3-5 per 1,000 procedures at 30 days of follow-up, “and if you look at individuals over 65, the rates almost double in terms of serious complications,” Dr. Lieberman, chief of the division of gastroenterology and hepatology at Oregon Health and Science University, said at the 2015 AGA Tech Summit, which is sponsored by the AGA Center for GI Innovation and Technology. “The rate of perforation over age 65 is about 1 per 1,000,” he said.

Colonoscopy is invasive, “and it would never be conceived of as the ideal test for population-based screening,” he added. “It’s expensive, and [clinicians] in many countries simply do not have the resources and expertise to do it.”

Compared with current screening rates in the United States for cervical and breast cancer, a “screening gap” exists in the percentage of adults who are up to date in tests for colorectal cancer, he said. “If you look at what’s been accomplished with cervical cancer screening and mammography, we see that there’s a ways to go for colonoscopy,” he said.

The ideal screening test for colorectal cancer would accurately identify individuals at risk for colon cancer at an early, preventable stage, Dr. Lieberman said. That prevention element “really averts the downstream colon cancer care costs, which would be very attractive in a single-payer health care system,” he said. “If we had a system that took care of us for life, that system would be very invested in trying to prevent colon cancer, because [it would] be worried about those downstream costs.”

One potential alternative to colonoscopy is fecal immunochemical testing (FIT). A recent meta-analysis suggested that FIT detected cancer with a 79% sensitivity (Ann. Intern. Med. 2014;160:171-81), and a separate, recent prospective study found a 74% sensitivity rate in detecting cancer, but a 24% sensitivity rate in detecting advanced adenoma (N. Engl. J. Med. 2014;370:1287-97). “So in terms of early detection, FIT is pretty good,” Dr. Lieberman said. “In terms of cancer prevention? Maybe not so good. There are also issues around the testing program, which requires adherence to both positive and negative tests. Some of these behavioral factors play a major role in the actual effectiveness. So you can have a great test, but if it’s not getting done properly then there’s going to be an issue. There is some potential for CRC prevention, but it’s going to be less than for some others.”

What about stool DNA? A landmark study found that stool DNA detected cancer with a sensitivity of 92%, compared with FIT at 74% (N. Engl. J Med. 2014;370:1287-97). However, the sensitivity for detecting adenomas was relatively low for both methods (42% for stool DNA, compared with 24% for FIT). Stool DNA testing “appears to be an effective screening test [but] the appropriate interval for testing is still uncertain,” Dr. Lieberman said. “The recommendation is a 3-year interval.”

He characterized serum testing as the “holy grail” of screening for colorectal cancer, “because it would be ideal to have a noninvasive test. You’d come in, get a blood draw, and get risk stratified. There are a number of different possible pathways, one looking at specific genetic markers, others looking at genetic fingerprinting: in other words, seeing a pattern of genes that are associated with colon cancer versus patients who do not have colon cancer. Proteomics is another fingerprinting technique, as is metabolomics: looking at a variety of metabolites that may be altered by the presence of having neoplasia. This is an intriguing area but so far there hasn’t been a lot of data.”

To date, the most progress involved in this area involves molecular tests of DNA or proteins. “These studies are all relatively small and somewhat promising in terms of cancer sensitivity, but not so great for adenoma sensitivity,” he said. “It’s fair to say that this is still a work in progress.”

Dr. Lieberman reported having served on the scientific advisory board of Exact Sciences.

In a separate presentation, Dr. Uri Ladabaum updated attendees on the status of PillCam, also known as colon capsule endoscopy (CCE), for detecting colon cancer. The PillCam is cleared by the Food and Drug Administration for detection of colon polyps in patients after an incomplete optical colonoscopy with adequate preparation, or if a complete evaluation of the colon was not technically possible. In a large meta-analysis, the first-generation PillCam achieved a sensitivity of 71% and a specificity of 75% in detecting polyps of any size and a sensitivity of 68% and a specificity of 82% in detecting polyps 6 mm in size or larger (Clin. Gastroenterol. Hepatol. 2010;8:515-22). “The results were somewhat disappointing for a test like this, not hitting the bar that we would want,” said Dr. Ladabaum, professor of medicine in the division of gastroenterology and hepatology at Stanford (Calif.) University.

The second generation PillCam features an improved angle of the imagers, from 156 degrees to 172 degrees, “so you get a bigger view all the way around,” he said. Another new feature is an adaptive imaging rate. The first-generation device captured 4 images per second regardless of where the capsule was moving. The new system “goes at 4 images per second when stationary, goes as fast as 35 imagers per second while moving, and 14 images per second before it reaches the small bowel,” Dr. Ladabaum said.

In an early study of the second-generation system, the device achieved a sensitivity of 89% and a specificity of 76% in detecting polyps of 6 mm in size or larger and a sensitivity of 88% and a specificity of 89% in detecting polyps 10 mm in size or larger (Endoscopy 2009;41:1026-31).

More recently, researchers examined consecutive patients who had incomplete colonoscopy and compared a follow-up with either second-generation CCE or CT colonography (Gut 2015;64:272-81). The diagnostic yield of CCE and CT colonography was 25% and 12%, respectively, for polyps 6 mm or larger and 5% vs. 3% for polyps 10 mm or larger.

In a larger, multisite study, researchers examined the efficacy of the second-generation PillCam as a primary screening tool (Gastroenterology 2015 [doi:10.1053/j.gastro.2015.01.025). Of 884 subjects enrolled, 85 were excluded from the analysis for a variety of reasons. Of these, 12 were excluded because the capsule did not reach the colon within 12 hours and 8 were excluded because the capsule did not pass the cecum within 12 hours. “So if used in practice, we’ll see this – [incomplete capsule studies],” Dr. Ladabaum said.

In addition, 77 were excluded for inadequate cleansing and capsule transit time through the colon in less than 40 minutes. “Maybe that’s due to the booster regimen,” he said. “There are still some things to work out in the bowel prep. Overall, there were a good number of people [in this study] who didn’t really have the exam [completed as intended]. Is that going to pan out as a big problem in clinical practice? That remains to be seen.”

The study found that the second-generation PillCam achieved a sensitivity of 87% and a specificity of 94% in detecting polyps 6 mm or larger and a sensitivity of 85% and a specificity of 97% in detecting polyps 10 mm in size or larger. “Is this good enough for this kind of technology?” Dr. Ladabaum asked. “There’s lots of room for debate here. Interestingly, the numbers for sessile serrated polyps didn’t look that good” (a sensitivity of 29% for polyps 6 mm in size or greater and 33% for polyps 10 mm in size or greater).

Dr. Ladabaum disclosed that he has served as a consultant for Given Imaging and Exact Sciences. He has also served on the advisory board for Mauna Kea Technologies.

In conclusion, according to Dr. Lieberman, there are several feasible alternatives to colonoscopy for primary colon cancer screening in average-risk individuals. Each has advantages and limitations and offers a less invasive approach to screening. The bar for screening has been raised from early cancer detection alone to both early detection and prevention. These less invasive tests will be expected to achieve accurate detection of individuals with early stage colon cancer and those at risk for colon cancer.

dbrunk@frontlinemedcom.com

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

©CDC

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

©CDC

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

©CDC

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Women with Crohn’s disease had about a 53% greater risk of developing cervical cancer compared with controls, and women with inflammatory bowel disease had a significantly greater risk of having had cervical neoplasia years earlier, according to a large population-based study reported in the April issue of Clinical Gastroenterology and Hepatology (http://dx.doi.org/10.1016/j.cgh.2014.07.036).

“We found a two-way association between inflammatory bowel disease, notably Crohn’s disease, and neoplastic lesions of the uterine cervix. This observation is not explained by differences in screening activity,” said Dr. Christine Rungoe at Statens Serum Institut in Copenhagen and her associates. “Patients with IBD should be encouraged to follow the screening program for cervical neoplasia, and clinicians should be aware of the slightly increased risk of HPV-related cervical lesions in IBD patients.”

Studies of IBD and cervical neoplasia have yielded mixed results as to a possible association. Some experts have postulated that underlying immunologic changes or the use of immunosuppressive drugs in IBD could thwart patients’ ability to clear HPV infections, thereby increasing their risk of developing cervical neoplasia. To explore that possibility, Dr. Rungoe and her associates compared rates of cervical dysplasia or cervical cancer among 27,408 women newly diagnosed with ulcerative colitis or Crohn’s disease and 1,508,334 controls without IBD. They identified cases and controls from a national patient registry of about 4 million women living in Denmark during 1979-2011. They also calculated the likelihood of a cervical neoplasia diagnosis preceding IBD.

Women with Crohn’s disease had a 26% higher rate of low-grade intraepithelial lesions of the cervix, a 28% greater incidence of high-grade lesions, and a 53% greater risk of cervical cancer compared with controls, the researchers reported (incidence rate ratios and 95% confidence intervals, respectively: 1.26, 1.07-1.48; 1.28, 1.13-1.45; and 1.53, 1.04-2.27). Women with ulcerative colitis also had about a 12%-15% increase in risk of developing cervical dysplasia, compared with controls (IRR for low-grade lesions, 1.15; 95% CI, 1.00-1.32; IRR for high-grade lesions, 1.12; 95% CI, 1.01-1.25), but no significant increase in cervical cancer risk.

Notably, women newly diagnosed with IBD had a “markedly elevated” odds of having been diagnosed with cervical neoplasia up to 10 years beforehand, the investigators reported. “This is a novel finding that may suggest a yet unexplored common susceptibility to IBD and cervical neoplasia, rather than an etiologic role of IBD or its treatment in development of cervical neoplasia,” they said.

Treatment with common IBD therapies such as azathioprine, mesalamine, and corticosteroids did not affect rates of cervical neoplasia, but women with Crohn’s disease who had used tumor necrosis factor–alpha antagonists had an 85% increase in high-grade intraepithelial cervical lesions. They also had a 2% increase in risk of these lesions for each filled prescription for hormonal contraceptives.

The frequency of cervical screening was slightly higher among women with ulcerative colitis, compared with controls, but was similar between controls and women with Crohn’s disease, the investigators noted.

The study was funded in part by the Danish Council of Independent Research. The investigators reported having no relevant financial disclosures.

Women with Crohn’s disease had about a 53% greater risk of developing cervical cancer compared with controls, and women with inflammatory bowel disease had a significantly greater risk of having had cervical neoplasia years earlier, according to a large population-based study reported in the April issue of Clinical Gastroenterology and Hepatology (http://dx.doi.org/10.1016/j.cgh.2014.07.036).

“We found a two-way association between inflammatory bowel disease, notably Crohn’s disease, and neoplastic lesions of the uterine cervix. This observation is not explained by differences in screening activity,” said Dr. Christine Rungoe at Statens Serum Institut in Copenhagen and her associates. “Patients with IBD should be encouraged to follow the screening program for cervical neoplasia, and clinicians should be aware of the slightly increased risk of HPV-related cervical lesions in IBD patients.”

Studies of IBD and cervical neoplasia have yielded mixed results as to a possible association. Some experts have postulated that underlying immunologic changes or the use of immunosuppressive drugs in IBD could thwart patients’ ability to clear HPV infections, thereby increasing their risk of developing cervical neoplasia. To explore that possibility, Dr. Rungoe and her associates compared rates of cervical dysplasia or cervical cancer among 27,408 women newly diagnosed with ulcerative colitis or Crohn’s disease and 1,508,334 controls without IBD. They identified cases and controls from a national patient registry of about 4 million women living in Denmark during 1979-2011. They also calculated the likelihood of a cervical neoplasia diagnosis preceding IBD.

Women with Crohn’s disease had a 26% higher rate of low-grade intraepithelial lesions of the cervix, a 28% greater incidence of high-grade lesions, and a 53% greater risk of cervical cancer compared with controls, the researchers reported (incidence rate ratios and 95% confidence intervals, respectively: 1.26, 1.07-1.48; 1.28, 1.13-1.45; and 1.53, 1.04-2.27). Women with ulcerative colitis also had about a 12%-15% increase in risk of developing cervical dysplasia, compared with controls (IRR for low-grade lesions, 1.15; 95% CI, 1.00-1.32; IRR for high-grade lesions, 1.12; 95% CI, 1.01-1.25), but no significant increase in cervical cancer risk.

Notably, women newly diagnosed with IBD had a “markedly elevated” odds of having been diagnosed with cervical neoplasia up to 10 years beforehand, the investigators reported. “This is a novel finding that may suggest a yet unexplored common susceptibility to IBD and cervical neoplasia, rather than an etiologic role of IBD or its treatment in development of cervical neoplasia,” they said.

Treatment with common IBD therapies such as azathioprine, mesalamine, and corticosteroids did not affect rates of cervical neoplasia, but women with Crohn’s disease who had used tumor necrosis factor–alpha antagonists had an 85% increase in high-grade intraepithelial cervical lesions. They also had a 2% increase in risk of these lesions for each filled prescription for hormonal contraceptives.

The frequency of cervical screening was slightly higher among women with ulcerative colitis, compared with controls, but was similar between controls and women with Crohn’s disease, the investigators noted.

The study was funded in part by the Danish Council of Independent Research. The investigators reported having no relevant financial disclosures.

Women with Crohn’s disease had about a 53% greater risk of developing cervical cancer compared with controls, and women with inflammatory bowel disease had a significantly greater risk of having had cervical neoplasia years earlier, according to a large population-based study reported in the April issue of Clinical Gastroenterology and Hepatology (http://dx.doi.org/10.1016/j.cgh.2014.07.036).

“We found a two-way association between inflammatory bowel disease, notably Crohn’s disease, and neoplastic lesions of the uterine cervix. This observation is not explained by differences in screening activity,” said Dr. Christine Rungoe at Statens Serum Institut in Copenhagen and her associates. “Patients with IBD should be encouraged to follow the screening program for cervical neoplasia, and clinicians should be aware of the slightly increased risk of HPV-related cervical lesions in IBD patients.”

Studies of IBD and cervical neoplasia have yielded mixed results as to a possible association. Some experts have postulated that underlying immunologic changes or the use of immunosuppressive drugs in IBD could thwart patients’ ability to clear HPV infections, thereby increasing their risk of developing cervical neoplasia. To explore that possibility, Dr. Rungoe and her associates compared rates of cervical dysplasia or cervical cancer among 27,408 women newly diagnosed with ulcerative colitis or Crohn’s disease and 1,508,334 controls without IBD. They identified cases and controls from a national patient registry of about 4 million women living in Denmark during 1979-2011. They also calculated the likelihood of a cervical neoplasia diagnosis preceding IBD.

Women with Crohn’s disease had a 26% higher rate of low-grade intraepithelial lesions of the cervix, a 28% greater incidence of high-grade lesions, and a 53% greater risk of cervical cancer compared with controls, the researchers reported (incidence rate ratios and 95% confidence intervals, respectively: 1.26, 1.07-1.48; 1.28, 1.13-1.45; and 1.53, 1.04-2.27). Women with ulcerative colitis also had about a 12%-15% increase in risk of developing cervical dysplasia, compared with controls (IRR for low-grade lesions, 1.15; 95% CI, 1.00-1.32; IRR for high-grade lesions, 1.12; 95% CI, 1.01-1.25), but no significant increase in cervical cancer risk.

Notably, women newly diagnosed with IBD had a “markedly elevated” odds of having been diagnosed with cervical neoplasia up to 10 years beforehand, the investigators reported. “This is a novel finding that may suggest a yet unexplored common susceptibility to IBD and cervical neoplasia, rather than an etiologic role of IBD or its treatment in development of cervical neoplasia,” they said.

Treatment with common IBD therapies such as azathioprine, mesalamine, and corticosteroids did not affect rates of cervical neoplasia, but women with Crohn’s disease who had used tumor necrosis factor–alpha antagonists had an 85% increase in high-grade intraepithelial cervical lesions. They also had a 2% increase in risk of these lesions for each filled prescription for hormonal contraceptives.

The frequency of cervical screening was slightly higher among women with ulcerative colitis, compared with controls, but was similar between controls and women with Crohn’s disease, the investigators noted.

The study was funded in part by the Danish Council of Independent Research. The investigators reported having no relevant financial disclosures.

BIRMINGHAM, ALA.– The time to colonoscopy after a positive fecal occult blood test varied widely between health systems and also varied based on age and comorbidity score, in a study of more than 62,000 patients from four health systems

The median time to colonoscopy after a positive fecal occult blood test (FOBT) in 62,384 patients in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) Network ranged from 41 to 174 days. Most of those who received a follow-up colonoscopy did so within 3-6 months of their positive FOBT.

GroupHealth Research Institute

The percentage of patients followed up with colonoscopy within 12 months ranged from 58.1% to 83.8%, with lowest percentages occurring in the two systems with the longest median time to follow-up, Jessica Chubak, Ph.D., of Group Health Research Institute and her colleagues reported in a poster at the American Society of Preventive Oncology annual meeting.

The rate of colonoscopy follow-up within 12 months also decreased with advancing age and increasing Charlson comorbidity score. For those aged 55-59 years, 60-64 years, 65-69 years, or 70-75 years, the hazard ratios for follow-up were 1.02, 0.98, 0.98, and 0.90, respectively, compared with the youngest age group (50-54 years). But for those patients aged 76-84 years or 85-89 years, the hazard ratios were 0.65 and 0.34, respectively.

For those with a Charlson comorbidity score of 1, 2, or 3 or more, the adjusted hazard ratios for follow-up of were 0.93, 0.87, and 0.70, respectively, compared with those with a score of 0, the investigators said.

No significant differences in follow-up were seen based on gender, body mass index, or race/ethnicity.

The investigators used administrative and clinical data to estimate the time to follow-up and probability of follow-up for all persons with a positive FOBT in 2011 and 2012.

The findings have implications for future research on improving follow-up in older patients and those with comorbidities, the study authors said.

The differences between health care systems may be due to varying practices. The two organizations with the best time to colonoscopy follow-up in the network are health maintenance organizations with targets for time to colonoscopy and monitored appointment supply.

In contrast, the organization with the second longest time to follow-up was an HMO that contracted with external providers for about 60% of colonoscopies. The organization with the longest time to follow-up was a safety-net system with limited colonoscopy capacity that served socioeconomically disadvantaged patients who may have faced more barriers to colonoscopy completion.

Colorectal cancer is the fourth most common cancer in the United States, and FOBT is an important screening strategy that relies on follow-up in the event of a positive finding.

“Our findings that both individual-level factors as well as health care system were associated with follow-up strengthens the rationale for investigating multilevel interventions to improve follow-up after abnormal screening tests,” the researchers concluded.

The National Cancer Institute funded the study.

BIRMINGHAM, ALA.– The time to colonoscopy after a positive fecal occult blood test varied widely between health systems and also varied based on age and comorbidity score, in a study of more than 62,000 patients from four health systems

The median time to colonoscopy after a positive fecal occult blood test (FOBT) in 62,384 patients in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) Network ranged from 41 to 174 days. Most of those who received a follow-up colonoscopy did so within 3-6 months of their positive FOBT.

GroupHealth Research Institute

The percentage of patients followed up with colonoscopy within 12 months ranged from 58.1% to 83.8%, with lowest percentages occurring in the two systems with the longest median time to follow-up, Jessica Chubak, Ph.D., of Group Health Research Institute and her colleagues reported in a poster at the American Society of Preventive Oncology annual meeting.

The rate of colonoscopy follow-up within 12 months also decreased with advancing age and increasing Charlson comorbidity score. For those aged 55-59 years, 60-64 years, 65-69 years, or 70-75 years, the hazard ratios for follow-up were 1.02, 0.98, 0.98, and 0.90, respectively, compared with the youngest age group (50-54 years). But for those patients aged 76-84 years or 85-89 years, the hazard ratios were 0.65 and 0.34, respectively.

For those with a Charlson comorbidity score of 1, 2, or 3 or more, the adjusted hazard ratios for follow-up of were 0.93, 0.87, and 0.70, respectively, compared with those with a score of 0, the investigators said.

No significant differences in follow-up were seen based on gender, body mass index, or race/ethnicity.

The investigators used administrative and clinical data to estimate the time to follow-up and probability of follow-up for all persons with a positive FOBT in 2011 and 2012.

The findings have implications for future research on improving follow-up in older patients and those with comorbidities, the study authors said.

The differences between health care systems may be due to varying practices. The two organizations with the best time to colonoscopy follow-up in the network are health maintenance organizations with targets for time to colonoscopy and monitored appointment supply.

In contrast, the organization with the second longest time to follow-up was an HMO that contracted with external providers for about 60% of colonoscopies. The organization with the longest time to follow-up was a safety-net system with limited colonoscopy capacity that served socioeconomically disadvantaged patients who may have faced more barriers to colonoscopy completion.

Colorectal cancer is the fourth most common cancer in the United States, and FOBT is an important screening strategy that relies on follow-up in the event of a positive finding.

“Our findings that both individual-level factors as well as health care system were associated with follow-up strengthens the rationale for investigating multilevel interventions to improve follow-up after abnormal screening tests,” the researchers concluded.

The National Cancer Institute funded the study.

BIRMINGHAM, ALA.– The time to colonoscopy after a positive fecal occult blood test varied widely between health systems and also varied based on age and comorbidity score, in a study of more than 62,000 patients from four health systems

The median time to colonoscopy after a positive fecal occult blood test (FOBT) in 62,384 patients in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) Network ranged from 41 to 174 days. Most of those who received a follow-up colonoscopy did so within 3-6 months of their positive FOBT.

GroupHealth Research Institute

The percentage of patients followed up with colonoscopy within 12 months ranged from 58.1% to 83.8%, with lowest percentages occurring in the two systems with the longest median time to follow-up, Jessica Chubak, Ph.D., of Group Health Research Institute and her colleagues reported in a poster at the American Society of Preventive Oncology annual meeting.

The rate of colonoscopy follow-up within 12 months also decreased with advancing age and increasing Charlson comorbidity score. For those aged 55-59 years, 60-64 years, 65-69 years, or 70-75 years, the hazard ratios for follow-up were 1.02, 0.98, 0.98, and 0.90, respectively, compared with the youngest age group (50-54 years). But for those patients aged 76-84 years or 85-89 years, the hazard ratios were 0.65 and 0.34, respectively.

For those with a Charlson comorbidity score of 1, 2, or 3 or more, the adjusted hazard ratios for follow-up of were 0.93, 0.87, and 0.70, respectively, compared with those with a score of 0, the investigators said.

No significant differences in follow-up were seen based on gender, body mass index, or race/ethnicity.

The investigators used administrative and clinical data to estimate the time to follow-up and probability of follow-up for all persons with a positive FOBT in 2011 and 2012.

The findings have implications for future research on improving follow-up in older patients and those with comorbidities, the study authors said.

The differences between health care systems may be due to varying practices. The two organizations with the best time to colonoscopy follow-up in the network are health maintenance organizations with targets for time to colonoscopy and monitored appointment supply.

In contrast, the organization with the second longest time to follow-up was an HMO that contracted with external providers for about 60% of colonoscopies. The organization with the longest time to follow-up was a safety-net system with limited colonoscopy capacity that served socioeconomically disadvantaged patients who may have faced more barriers to colonoscopy completion.

Colorectal cancer is the fourth most common cancer in the United States, and FOBT is an important screening strategy that relies on follow-up in the event of a positive finding.

“Our findings that both individual-level factors as well as health care system were associated with follow-up strengthens the rationale for investigating multilevel interventions to improve follow-up after abnormal screening tests,” the researchers concluded.

The National Cancer Institute funded the study.

A mixture of eight probiotic bacterial strains only somewhat outperformed placebo for preventing endoscopic recurrence after ileal resection in Crohn’s disease patients, according to a multicenter, randomized trial.

After 90 days of treatment, 9.3% of patients who received the probiotic mixture (VSL#3) had developed severe endoscopic recurrence, compared with 15.7% of the placebo group (P = .19), reported Dr. Richard Fedorak of the University of Alberta, Edmonton, and his associates.

The recurrence rate for the placebo group was about two-thirds lower than what the researchers had expected based on the sample size calculation, they noted. But the probiotic blend was linked to significantly significant decreases in colonic mucosal levels of proinflammatory cytokines, they reported (Clin. Gastroenterol. Hepatol. 2014 Nov. 6 [doi:10.1016/j.cgh.2014.10.031]).

Investigators have tested probiotics as a preventive therapy for Crohn’s disease because patients with active disease have less diverse intestinal microbiota, compared with those with quiescent disease or healthy controls. Past studies of single-strain probiotics have shown them to be no better than placebo for preventing endoscopic recurrence.

But in one small study, rifampin followed by VSL#3 outperformed mesalamine at 1 year (Gastroenterology 2000;118:A781), the researchers noted. “This mixture could confer protective effects where single-strain or lactobacillus-only formulations had failed,” they hypothesized.

To test that theory, the investigators randomized 120 patients with Crohn’s disease who had undergone ileal resection and ileocolonic anastomosis to twice-daily VSL#3 or placebo. Treatment began within 30 days after surgery and continued for 90 days, after which all patients received open-label VSL#3 for another 9 months.

Among patients who had nonsevere endoscopic lesions at day 90, 1-year rates of severe endoscopic recurrence were 10% for the early VSL#3 group, compared with 26.7% for the late VSL#3 group (P = .09), said the researchers. Likewise, combined rates of severe recurrence on days 90 and 365 were not statistically different, they reported. However, the early VSL#3 group had lower mucosal levels of 13 pro-inflammatory cytokines, compared with patients who received placebo until day 90 (P < .05). Measures of Crohn’s disease activity and disease-related quality of life scores were similar for both groups.

“Early treatment with VSL#3 had a larger effect than late treatment,” concluded the investigators. “Future larger studies will be needed to confirm the effect of VSL#3 in prevention of postoperative recurrence.”

The study was funded by VSL Pharmaceuticals, the Canadian Institutes of Health Research, and Crohn’s and Colitis Foundation of Canada. Dr. Fedorak reported having served on a speakers bureau for VSL Pharmaceuticals. The other authors declared no relevant conflicts of interest.

A mixture of eight probiotic bacterial strains only somewhat outperformed placebo for preventing endoscopic recurrence after ileal resection in Crohn’s disease patients, according to a multicenter, randomized trial.

After 90 days of treatment, 9.3% of patients who received the probiotic mixture (VSL#3) had developed severe endoscopic recurrence, compared with 15.7% of the placebo group (P = .19), reported Dr. Richard Fedorak of the University of Alberta, Edmonton, and his associates.

The recurrence rate for the placebo group was about two-thirds lower than what the researchers had expected based on the sample size calculation, they noted. But the probiotic blend was linked to significantly significant decreases in colonic mucosal levels of proinflammatory cytokines, they reported (Clin. Gastroenterol. Hepatol. 2014 Nov. 6 [doi:10.1016/j.cgh.2014.10.031]).

Investigators have tested probiotics as a preventive therapy for Crohn’s disease because patients with active disease have less diverse intestinal microbiota, compared with those with quiescent disease or healthy controls. Past studies of single-strain probiotics have shown them to be no better than placebo for preventing endoscopic recurrence.

But in one small study, rifampin followed by VSL#3 outperformed mesalamine at 1 year (Gastroenterology 2000;118:A781), the researchers noted. “This mixture could confer protective effects where single-strain or lactobacillus-only formulations had failed,” they hypothesized.

To test that theory, the investigators randomized 120 patients with Crohn’s disease who had undergone ileal resection and ileocolonic anastomosis to twice-daily VSL#3 or placebo. Treatment began within 30 days after surgery and continued for 90 days, after which all patients received open-label VSL#3 for another 9 months.

Among patients who had nonsevere endoscopic lesions at day 90, 1-year rates of severe endoscopic recurrence were 10% for the early VSL#3 group, compared with 26.7% for the late VSL#3 group (P = .09), said the researchers. Likewise, combined rates of severe recurrence on days 90 and 365 were not statistically different, they reported. However, the early VSL#3 group had lower mucosal levels of 13 pro-inflammatory cytokines, compared with patients who received placebo until day 90 (P < .05). Measures of Crohn’s disease activity and disease-related quality of life scores were similar for both groups.

“Early treatment with VSL#3 had a larger effect than late treatment,” concluded the investigators. “Future larger studies will be needed to confirm the effect of VSL#3 in prevention of postoperative recurrence.”

The study was funded by VSL Pharmaceuticals, the Canadian Institutes of Health Research, and Crohn’s and Colitis Foundation of Canada. Dr. Fedorak reported having served on a speakers bureau for VSL Pharmaceuticals. The other authors declared no relevant conflicts of interest.

A mixture of eight probiotic bacterial strains only somewhat outperformed placebo for preventing endoscopic recurrence after ileal resection in Crohn’s disease patients, according to a multicenter, randomized trial.

After 90 days of treatment, 9.3% of patients who received the probiotic mixture (VSL#3) had developed severe endoscopic recurrence, compared with 15.7% of the placebo group (P = .19), reported Dr. Richard Fedorak of the University of Alberta, Edmonton, and his associates.

The recurrence rate for the placebo group was about two-thirds lower than what the researchers had expected based on the sample size calculation, they noted. But the probiotic blend was linked to significantly significant decreases in colonic mucosal levels of proinflammatory cytokines, they reported (Clin. Gastroenterol. Hepatol. 2014 Nov. 6 [doi:10.1016/j.cgh.2014.10.031]).

Investigators have tested probiotics as a preventive therapy for Crohn’s disease because patients with active disease have less diverse intestinal microbiota, compared with those with quiescent disease or healthy controls. Past studies of single-strain probiotics have shown them to be no better than placebo for preventing endoscopic recurrence.

But in one small study, rifampin followed by VSL#3 outperformed mesalamine at 1 year (Gastroenterology 2000;118:A781), the researchers noted. “This mixture could confer protective effects where single-strain or lactobacillus-only formulations had failed,” they hypothesized.

To test that theory, the investigators randomized 120 patients with Crohn’s disease who had undergone ileal resection and ileocolonic anastomosis to twice-daily VSL#3 or placebo. Treatment began within 30 days after surgery and continued for 90 days, after which all patients received open-label VSL#3 for another 9 months.

Among patients who had nonsevere endoscopic lesions at day 90, 1-year rates of severe endoscopic recurrence were 10% for the early VSL#3 group, compared with 26.7% for the late VSL#3 group (P = .09), said the researchers. Likewise, combined rates of severe recurrence on days 90 and 365 were not statistically different, they reported. However, the early VSL#3 group had lower mucosal levels of 13 pro-inflammatory cytokines, compared with patients who received placebo until day 90 (P < .05). Measures of Crohn’s disease activity and disease-related quality of life scores were similar for both groups.

“Early treatment with VSL#3 had a larger effect than late treatment,” concluded the investigators. “Future larger studies will be needed to confirm the effect of VSL#3 in prevention of postoperative recurrence.”

The study was funded by VSL Pharmaceuticals, the Canadian Institutes of Health Research, and Crohn’s and Colitis Foundation of Canada. Dr. Fedorak reported having served on a speakers bureau for VSL Pharmaceuticals. The other authors declared no relevant conflicts of interest.

Humans can host up to 6 pounds of microbes in our gut alone. We comprise about 10 trillion human cells – they comprise 100 trillion bacterial cells. Their genetic material outstrips us even more impressively – we are the product of 20,000 human genes. But inside our gut, we carry up to 2 million microbial genes.

Emerging research suggests that these complex communities – which interact fluidly not only with their human host, but also with each other – play important roles in health and disease. They appear to confer both protection from and risk for many chronic illnesses, from asthma and allergies to obesity and diabetes.

And what we don’t know about them dwarfs what we do know, according to Dr. Robert Ratner, the chief medical officer of the American Diabetes Association.

“We’re literally at the forefront of an unknown universe,” Dr. Ratner said at the annual advanced postgraduate course held by the ADA. “Research into the microbiome and how it interacts with human health is one of our most intriguing investigations.”

The microbiome is as vastly individual as every person who carries it. The differences are myriad, in the amount and variety of species, and in the sheer numbers of microbes that make up each community. Each region of the gut, from mouth to rectum, hosts a completely different population.

Two main phyla populate the gut: Bacteroidetes, which are involved in protein and carbohydrate breakdown, and Firmicutes, which promote the absorption of fat. The ratios of these communities, however, has changed over the last 30 years, diverging along a path that mirrors global spikes in obesity, diabetes, and allergic and inflammatory disorders.

“We have seen dramatic increases worldwide in these disorders,” Dr. Ratner said. “We’ve also seen decreased diversity of the microbiome, with a progressive change in density from Bacteroidetes to Firmicutes. These are associations – not causations – but I think the time has come to ask ‘What are we doing to change these bacteria?’ ”

The rampant use of antibiotics is the first place suspicion falls – and it’s no wonder, since the epidemiologic changes Dr. Ratner described began to appear shortly after World War II. Antibiotics could exert their flora-changing effects a couple of ways, he noted.

They directly alter the composition of communities in the person who consumes the drug, even if just in the short-term. There is someevidence that early-life antibiotics, though changing the microbiome only temporarily, can change fat metabolism for the entire lifespan (Cell 2014;158:705-21).

The associations between an altered gut microbiome and long-term health is unproven. But a picture does seem to emerge when viewed in light of the exponential increases in obesity and its attendant rise in diabetes.

The Type 1 Diabetes Prediction and Prevention Project (DIPP) is an effort to predict and search for means to delay or prevent type 1 diabetes. Launched in 1994, it’s following a cohort of children who had genetic risk factors for type 1 diabetes. Data have consistently shown that those who develop the disease have significantly lower diversity in their gut flora, Dr. Ratner said. Certain species of Bacteroides increased the risk of autoimmunity by up to 20 times.

Again, he said, this is association, not causation. But some very new evidence suggests that these are functional, not just observational, links. “It does now appear that our microbes are actually controlling our metabolism,” he said. “Some of these species liberate lipopolysaccharides, which function as endotoxins. These cross the mucosal barrier in the intestine, enter the interstitial space, and set up an inflammation that impacts the liver and adipocytes, potentially decreasing insulin sensitivity.”

Unpublished data from the laboratory of Dr. Martin J. Blaser at New York University show for the first time that a specific bacterium can cause diabetes, and removing it cures the disease. The bacterium in question, Ralstonia, is a gram-negative pathogen that contaminates drinking water. Mice engineered as a model of prediabetes gained much more weight when they consumed live Ralstonia than when they got a heat-inactivated version. They also developed insulin resistance and hyperglycemia in the presence of the live version. But when the same mice were given a Ralstonia antibody, they lost weight and their glycemic profile normalized.

“This is the first direct evidence we have of causality,” Dr. Ratner said.

Strong evidence of causation is also emerging in the surgical realm. Roux-en-Y gastric bypass seems to change the microbiome in a way that facilitates weight loss, beyond caloric intake.Randy Seeley, Ph.D., of the University of Michigan, Ann Arbor, has been studying how weight-loss surgery affects the microbiome. He theorizes that the physical manipulation of the gut induces what he calls “enteroplasticity” – a fluid adaptation of both the gut’s structure and its bacterial communities to the altered physical and chemical environment. “There’s more going on during postsurgical weight loss than just food restriction and malabsorption,” Dr. Seeley said in an interview. “It’s logical to think that when you do this kind of surgery, the microbes in the intestine will change.”

Roseburia intestinalis is a Firmicute that typically increases after bariatric surgery. It’s also found to be deficient in people who have diabetes. Dr. Seeley coauthored an article showing that Roseburia and other beneficial firmicutes increased significantly in mice that underwent vertical sleeve gastrectomy (Nature 2014;509:183-8). These mice lost weight after surgery, as would be expected, but then showed a preference for the high-protein and carbohydrate-rich foods that Firmicutes need. Their microbiome also showed decreases in the concentration of fat-loving Bacteroides species.

But interestingly, weight loss and microbiome improvement happened only in mice that had a normal bile acid–signaling system. Immediately after surgery, mice engineered to lack bile acid receptors did eat less and lose weight. But a week later, their appetites came back full force, and they actually seemed driven to eat fat. They quickly returned to their presurgical weight. Their microbiome didn’t show the same improvement as their cousins with normal signaling pathways, suggesting that a complex interaction between bacteria and the gut’s physical alteration may be driving weight loss.

“Is weight-loss surgery, then, fixing this ‘broken’ component of the microbiome?” Dr. Seeley asked. “Is Roseburia the causal agent of improvement? Or is it a marker of improvement in an entire community? I would say it’s probably the entire community changing, and changing its interaction with its host organism.”

Dr. Seeley disclosed that he has received financial support from Johnson & Johnson, Novo Nordisk, and Eisai.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Humans can host up to 6 pounds of microbes in our gut alone. We comprise about 10 trillion human cells – they comprise 100 trillion bacterial cells. Their genetic material outstrips us even more impressively – we are the product of 20,000 human genes. But inside our gut, we carry up to 2 million microbial genes.

Emerging research suggests that these complex communities – which interact fluidly not only with their human host, but also with each other – play important roles in health and disease. They appear to confer both protection from and risk for many chronic illnesses, from asthma and allergies to obesity and diabetes.

And what we don’t know about them dwarfs what we do know, according to Dr. Robert Ratner, the chief medical officer of the American Diabetes Association.

“We’re literally at the forefront of an unknown universe,” Dr. Ratner said at the annual advanced postgraduate course held by the ADA. “Research into the microbiome and how it interacts with human health is one of our most intriguing investigations.”

The microbiome is as vastly individual as every person who carries it. The differences are myriad, in the amount and variety of species, and in the sheer numbers of microbes that make up each community. Each region of the gut, from mouth to rectum, hosts a completely different population.

Two main phyla populate the gut: Bacteroidetes, which are involved in protein and carbohydrate breakdown, and Firmicutes, which promote the absorption of fat. The ratios of these communities, however, has changed over the last 30 years, diverging along a path that mirrors global spikes in obesity, diabetes, and allergic and inflammatory disorders.

“We have seen dramatic increases worldwide in these disorders,” Dr. Ratner said. “We’ve also seen decreased diversity of the microbiome, with a progressive change in density from Bacteroidetes to Firmicutes. These are associations – not causations – but I think the time has come to ask ‘What are we doing to change these bacteria?’ ”

The rampant use of antibiotics is the first place suspicion falls – and it’s no wonder, since the epidemiologic changes Dr. Ratner described began to appear shortly after World War II. Antibiotics could exert their flora-changing effects a couple of ways, he noted.

They directly alter the composition of communities in the person who consumes the drug, even if just in the short-term. There is someevidence that early-life antibiotics, though changing the microbiome only temporarily, can change fat metabolism for the entire lifespan (Cell 2014;158:705-21).

The associations between an altered gut microbiome and long-term health is unproven. But a picture does seem to emerge when viewed in light of the exponential increases in obesity and its attendant rise in diabetes.

The Type 1 Diabetes Prediction and Prevention Project (DIPP) is an effort to predict and search for means to delay or prevent type 1 diabetes. Launched in 1994, it’s following a cohort of children who had genetic risk factors for type 1 diabetes. Data have consistently shown that those who develop the disease have significantly lower diversity in their gut flora, Dr. Ratner said. Certain species of Bacteroides increased the risk of autoimmunity by up to 20 times.

Again, he said, this is association, not causation. But some very new evidence suggests that these are functional, not just observational, links. “It does now appear that our microbes are actually controlling our metabolism,” he said. “Some of these species liberate lipopolysaccharides, which function as endotoxins. These cross the mucosal barrier in the intestine, enter the interstitial space, and set up an inflammation that impacts the liver and adipocytes, potentially decreasing insulin sensitivity.”

Unpublished data from the laboratory of Dr. Martin J. Blaser at New York University show for the first time that a specific bacterium can cause diabetes, and removing it cures the disease. The bacterium in question, Ralstonia, is a gram-negative pathogen that contaminates drinking water. Mice engineered as a model of prediabetes gained much more weight when they consumed live Ralstonia than when they got a heat-inactivated version. They also developed insulin resistance and hyperglycemia in the presence of the live version. But when the same mice were given a Ralstonia antibody, they lost weight and their glycemic profile normalized.

“This is the first direct evidence we have of causality,” Dr. Ratner said.

Strong evidence of causation is also emerging in the surgical realm. Roux-en-Y gastric bypass seems to change the microbiome in a way that facilitates weight loss, beyond caloric intake.Randy Seeley, Ph.D., of the University of Michigan, Ann Arbor, has been studying how weight-loss surgery affects the microbiome. He theorizes that the physical manipulation of the gut induces what he calls “enteroplasticity” – a fluid adaptation of both the gut’s structure and its bacterial communities to the altered physical and chemical environment. “There’s more going on during postsurgical weight loss than just food restriction and malabsorption,” Dr. Seeley said in an interview. “It’s logical to think that when you do this kind of surgery, the microbes in the intestine will change.”

Roseburia intestinalis is a Firmicute that typically increases after bariatric surgery. It’s also found to be deficient in people who have diabetes. Dr. Seeley coauthored an article showing that Roseburia and other beneficial firmicutes increased significantly in mice that underwent vertical sleeve gastrectomy (Nature 2014;509:183-8). These mice lost weight after surgery, as would be expected, but then showed a preference for the high-protein and carbohydrate-rich foods that Firmicutes need. Their microbiome also showed decreases in the concentration of fat-loving Bacteroides species.

But interestingly, weight loss and microbiome improvement happened only in mice that had a normal bile acid–signaling system. Immediately after surgery, mice engineered to lack bile acid receptors did eat less and lose weight. But a week later, their appetites came back full force, and they actually seemed driven to eat fat. They quickly returned to their presurgical weight. Their microbiome didn’t show the same improvement as their cousins with normal signaling pathways, suggesting that a complex interaction between bacteria and the gut’s physical alteration may be driving weight loss.

“Is weight-loss surgery, then, fixing this ‘broken’ component of the microbiome?” Dr. Seeley asked. “Is Roseburia the causal agent of improvement? Or is it a marker of improvement in an entire community? I would say it’s probably the entire community changing, and changing its interaction with its host organism.”

Dr. Seeley disclosed that he has received financial support from Johnson & Johnson, Novo Nordisk, and Eisai.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Humans can host up to 6 pounds of microbes in our gut alone. We comprise about 10 trillion human cells – they comprise 100 trillion bacterial cells. Their genetic material outstrips us even more impressively – we are the product of 20,000 human genes. But inside our gut, we carry up to 2 million microbial genes.

Emerging research suggests that these complex communities – which interact fluidly not only with their human host, but also with each other – play important roles in health and disease. They appear to confer both protection from and risk for many chronic illnesses, from asthma and allergies to obesity and diabetes.

And what we don’t know about them dwarfs what we do know, according to Dr. Robert Ratner, the chief medical officer of the American Diabetes Association.

“We’re literally at the forefront of an unknown universe,” Dr. Ratner said at the annual advanced postgraduate course held by the ADA. “Research into the microbiome and how it interacts with human health is one of our most intriguing investigations.”

The microbiome is as vastly individual as every person who carries it. The differences are myriad, in the amount and variety of species, and in the sheer numbers of microbes that make up each community. Each region of the gut, from mouth to rectum, hosts a completely different population.

Two main phyla populate the gut: Bacteroidetes, which are involved in protein and carbohydrate breakdown, and Firmicutes, which promote the absorption of fat. The ratios of these communities, however, has changed over the last 30 years, diverging along a path that mirrors global spikes in obesity, diabetes, and allergic and inflammatory disorders.

“We have seen dramatic increases worldwide in these disorders,” Dr. Ratner said. “We’ve also seen decreased diversity of the microbiome, with a progressive change in density from Bacteroidetes to Firmicutes. These are associations – not causations – but I think the time has come to ask ‘What are we doing to change these bacteria?’ ”

The rampant use of antibiotics is the first place suspicion falls – and it’s no wonder, since the epidemiologic changes Dr. Ratner described began to appear shortly after World War II. Antibiotics could exert their flora-changing effects a couple of ways, he noted.

They directly alter the composition of communities in the person who consumes the drug, even if just in the short-term. There is someevidence that early-life antibiotics, though changing the microbiome only temporarily, can change fat metabolism for the entire lifespan (Cell 2014;158:705-21).

The associations between an altered gut microbiome and long-term health is unproven. But a picture does seem to emerge when viewed in light of the exponential increases in obesity and its attendant rise in diabetes.

The Type 1 Diabetes Prediction and Prevention Project (DIPP) is an effort to predict and search for means to delay or prevent type 1 diabetes. Launched in 1994, it’s following a cohort of children who had genetic risk factors for type 1 diabetes. Data have consistently shown that those who develop the disease have significantly lower diversity in their gut flora, Dr. Ratner said. Certain species of Bacteroides increased the risk of autoimmunity by up to 20 times.

Again, he said, this is association, not causation. But some very new evidence suggests that these are functional, not just observational, links. “It does now appear that our microbes are actually controlling our metabolism,” he said. “Some of these species liberate lipopolysaccharides, which function as endotoxins. These cross the mucosal barrier in the intestine, enter the interstitial space, and set up an inflammation that impacts the liver and adipocytes, potentially decreasing insulin sensitivity.”

Unpublished data from the laboratory of Dr. Martin J. Blaser at New York University show for the first time that a specific bacterium can cause diabetes, and removing it cures the disease. The bacterium in question, Ralstonia, is a gram-negative pathogen that contaminates drinking water. Mice engineered as a model of prediabetes gained much more weight when they consumed live Ralstonia than when they got a heat-inactivated version. They also developed insulin resistance and hyperglycemia in the presence of the live version. But when the same mice were given a Ralstonia antibody, they lost weight and their glycemic profile normalized.

“This is the first direct evidence we have of causality,” Dr. Ratner said.

Strong evidence of causation is also emerging in the surgical realm. Roux-en-Y gastric bypass seems to change the microbiome in a way that facilitates weight loss, beyond caloric intake.Randy Seeley, Ph.D., of the University of Michigan, Ann Arbor, has been studying how weight-loss surgery affects the microbiome. He theorizes that the physical manipulation of the gut induces what he calls “enteroplasticity” – a fluid adaptation of both the gut’s structure and its bacterial communities to the altered physical and chemical environment. “There’s more going on during postsurgical weight loss than just food restriction and malabsorption,” Dr. Seeley said in an interview. “It’s logical to think that when you do this kind of surgery, the microbes in the intestine will change.”

Roseburia intestinalis is a Firmicute that typically increases after bariatric surgery. It’s also found to be deficient in people who have diabetes. Dr. Seeley coauthored an article showing that Roseburia and other beneficial firmicutes increased significantly in mice that underwent vertical sleeve gastrectomy (Nature 2014;509:183-8). These mice lost weight after surgery, as would be expected, but then showed a preference for the high-protein and carbohydrate-rich foods that Firmicutes need. Their microbiome also showed decreases in the concentration of fat-loving Bacteroides species.

But interestingly, weight loss and microbiome improvement happened only in mice that had a normal bile acid–signaling system. Immediately after surgery, mice engineered to lack bile acid receptors did eat less and lose weight. But a week later, their appetites came back full force, and they actually seemed driven to eat fat. They quickly returned to their presurgical weight. Their microbiome didn’t show the same improvement as their cousins with normal signaling pathways, suggesting that a complex interaction between bacteria and the gut’s physical alteration may be driving weight loss.

“Is weight-loss surgery, then, fixing this ‘broken’ component of the microbiome?” Dr. Seeley asked. “Is Roseburia the causal agent of improvement? Or is it a marker of improvement in an entire community? I would say it’s probably the entire community changing, and changing its interaction with its host organism.”

Dr. Seeley disclosed that he has received financial support from Johnson & Johnson, Novo Nordisk, and Eisai.

msullivan@frontlinemedcom.com

On Twitter @alz_gal