Endoscopy, Pancreas, & Biliary Tract

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

Neither time of day, nor number of procedures performed by the clinician impacted adenoma detection rates in a large community-based setting, a study has shown.

Previously, mixed and scanty data on whether endoscopist fatigue correlates with colonoscopy quality in a community-based setting – where the majority of colonoscopies are performed – brought into question the link between a clinician’s detection rates and patient mortality rates due to interval cancers. Colorectal cancer is the second leading cause of cancer death in the U.S.

The most recent recommended adenoma detection rates – considered benchmarks of colonoscopic quality – are at or above 20% in men and at or above 30% in women, according to the American College of Gastroenterology.

A new study published online in Gastrointestinal Endoscopy, however, indicates that the endoscopists working in a large, integrated, community-based health care system exceeded those quality benchmarks.

Gastroenterologist Alexander T. Lee, MD, and his colleagues identified 126 gastroenterologists in the health system, Kaiser Permanente Northern California, who performed an average of six endoscopy procedures per day – 259,064 in all – between 2010 and 2013, including 76,445 screenings and surveillance colonoscopies. They found that per physician, adenoma detection rates for screening colonoscopy examinations averaged 28.9% and 45.4% for surveillance examinations. By patient gender, the average detection rates per screening were 34.8% for men and 24.0% for women; detection rates per surveillance, the rates were 51.1% for men and 37.8% for women.

After adjusting for confounders, the investigators analyzed each physician’s average adenoma detection rates in association with the time of day each GI procedure was performed, the number of GI procedures performed before each colonoscopy, and the level of complexity of any prior procedures performed at the time of the screening or surveillance colonoscopy. Dr. Lee and his coinvestigators also found that compared with morning examinations, afternoon colonoscopies were not associated with lower adenoma detection for screening examinations, surveillance examinations, or their combination (odds ratio for combination, 0.99; 95% confidence interval, 0.96-1.03). Additionally, neither the number of procedures performed before a given colonoscopy, nor a prior procedure’s complexity, was inversely associated with adenoma detection (OR for detection rates late in the day vs. first procedure of the day, 0.99; 95% CI, 0.94-1.04).

In systems where physicians have larger daily GI procedure loads, there could be an adverse impact on adenoma detection rates, wrote Dr. Lee and his coauthors, but they also noted that quality could similarly be diluted by a lower ratio of procedures to clinician, as well. Whether other demands on a physician’s time, such as other clinical procedures or office tasks, might adversely impact detection rates, Dr. Lee and his colleagues didn’t know because they measured only the colonoscopic screening and surveillance activities. “The reported lack of an association with time of day would argue against this being a substantial factor in [this] study,” they wrote.

“The fact that increased adenoma detection was found only for screening colonoscopy examinations raises the question of whether endoscopists were systematically more vigilant during screening procedures, although the higher observed adenoma detection rates for surveillance examinations suggest otherwise,” the investigators wrote.

None of the investigators listed had any relevant disclosures.
 

[email protected]

On Twitter @whitneymcknight

Neither time of day, nor number of procedures performed by the clinician impacted adenoma detection rates in a large community-based setting, a study has shown.

Previously, mixed and scanty data on whether endoscopist fatigue correlates with colonoscopy quality in a community-based setting – where the majority of colonoscopies are performed – brought into question the link between a clinician’s detection rates and patient mortality rates due to interval cancers. Colorectal cancer is the second leading cause of cancer death in the U.S.

The most recent recommended adenoma detection rates – considered benchmarks of colonoscopic quality – are at or above 20% in men and at or above 30% in women, according to the American College of Gastroenterology.

A new study published online in Gastrointestinal Endoscopy, however, indicates that the endoscopists working in a large, integrated, community-based health care system exceeded those quality benchmarks.

Gastroenterologist Alexander T. Lee, MD, and his colleagues identified 126 gastroenterologists in the health system, Kaiser Permanente Northern California, who performed an average of six endoscopy procedures per day – 259,064 in all – between 2010 and 2013, including 76,445 screenings and surveillance colonoscopies. They found that per physician, adenoma detection rates for screening colonoscopy examinations averaged 28.9% and 45.4% for surveillance examinations. By patient gender, the average detection rates per screening were 34.8% for men and 24.0% for women; detection rates per surveillance, the rates were 51.1% for men and 37.8% for women.

After adjusting for confounders, the investigators analyzed each physician’s average adenoma detection rates in association with the time of day each GI procedure was performed, the number of GI procedures performed before each colonoscopy, and the level of complexity of any prior procedures performed at the time of the screening or surveillance colonoscopy. Dr. Lee and his coinvestigators also found that compared with morning examinations, afternoon colonoscopies were not associated with lower adenoma detection for screening examinations, surveillance examinations, or their combination (odds ratio for combination, 0.99; 95% confidence interval, 0.96-1.03). Additionally, neither the number of procedures performed before a given colonoscopy, nor a prior procedure’s complexity, was inversely associated with adenoma detection (OR for detection rates late in the day vs. first procedure of the day, 0.99; 95% CI, 0.94-1.04).

In systems where physicians have larger daily GI procedure loads, there could be an adverse impact on adenoma detection rates, wrote Dr. Lee and his coauthors, but they also noted that quality could similarly be diluted by a lower ratio of procedures to clinician, as well. Whether other demands on a physician’s time, such as other clinical procedures or office tasks, might adversely impact detection rates, Dr. Lee and his colleagues didn’t know because they measured only the colonoscopic screening and surveillance activities. “The reported lack of an association with time of day would argue against this being a substantial factor in [this] study,” they wrote.

“The fact that increased adenoma detection was found only for screening colonoscopy examinations raises the question of whether endoscopists were systematically more vigilant during screening procedures, although the higher observed adenoma detection rates for surveillance examinations suggest otherwise,” the investigators wrote.

None of the investigators listed had any relevant disclosures.
 

[email protected]

On Twitter @whitneymcknight

Neither time of day, nor number of procedures performed by the clinician impacted adenoma detection rates in a large community-based setting, a study has shown.

Previously, mixed and scanty data on whether endoscopist fatigue correlates with colonoscopy quality in a community-based setting – where the majority of colonoscopies are performed – brought into question the link between a clinician’s detection rates and patient mortality rates due to interval cancers. Colorectal cancer is the second leading cause of cancer death in the U.S.

The most recent recommended adenoma detection rates – considered benchmarks of colonoscopic quality – are at or above 20% in men and at or above 30% in women, according to the American College of Gastroenterology.

A new study published online in Gastrointestinal Endoscopy, however, indicates that the endoscopists working in a large, integrated, community-based health care system exceeded those quality benchmarks.

Gastroenterologist Alexander T. Lee, MD, and his colleagues identified 126 gastroenterologists in the health system, Kaiser Permanente Northern California, who performed an average of six endoscopy procedures per day – 259,064 in all – between 2010 and 2013, including 76,445 screenings and surveillance colonoscopies. They found that per physician, adenoma detection rates for screening colonoscopy examinations averaged 28.9% and 45.4% for surveillance examinations. By patient gender, the average detection rates per screening were 34.8% for men and 24.0% for women; detection rates per surveillance, the rates were 51.1% for men and 37.8% for women.

After adjusting for confounders, the investigators analyzed each physician’s average adenoma detection rates in association with the time of day each GI procedure was performed, the number of GI procedures performed before each colonoscopy, and the level of complexity of any prior procedures performed at the time of the screening or surveillance colonoscopy. Dr. Lee and his coinvestigators also found that compared with morning examinations, afternoon colonoscopies were not associated with lower adenoma detection for screening examinations, surveillance examinations, or their combination (odds ratio for combination, 0.99; 95% confidence interval, 0.96-1.03). Additionally, neither the number of procedures performed before a given colonoscopy, nor a prior procedure’s complexity, was inversely associated with adenoma detection (OR for detection rates late in the day vs. first procedure of the day, 0.99; 95% CI, 0.94-1.04).

In systems where physicians have larger daily GI procedure loads, there could be an adverse impact on adenoma detection rates, wrote Dr. Lee and his coauthors, but they also noted that quality could similarly be diluted by a lower ratio of procedures to clinician, as well. Whether other demands on a physician’s time, such as other clinical procedures or office tasks, might adversely impact detection rates, Dr. Lee and his colleagues didn’t know because they measured only the colonoscopic screening and surveillance activities. “The reported lack of an association with time of day would argue against this being a substantial factor in [this] study,” they wrote.

“The fact that increased adenoma detection was found only for screening colonoscopy examinations raises the question of whether endoscopists were systematically more vigilant during screening procedures, although the higher observed adenoma detection rates for surveillance examinations suggest otherwise,” the investigators wrote.

None of the investigators listed had any relevant disclosures.
 

[email protected]

On Twitter @whitneymcknight

NEW ORLEANS – Early weight loss on liraglutide – specifically, dropping at least 4% of body weight at 16 weeks – is a strong and clinically useful identifier of patients with a high likelihood of significant weight loss 13 months into treatment, with an accompanying improvement in cardiometabolic risk factors, according to Ken Fujioka, MD.

Conversely, patients who aren’t early responders to subcutaneous liraglutide at 3 mg/day are unlikely to achieve at least 5% weight loss after a full year on the drug, the regulatory benchmark for clinically meaningful weight loss, added Dr. Fujioka, an internist and director of the center for weight management at the Scripps Clinic in La Jolla, Calif.

“Using this early response criterion at week 16 to predict long-term weight loss is to me a very valuable tool. Obesity is an odd disease because it has so many different causes. Finding the right drug is tough, and how long to keep trying with a particular medication is something we haven’t known. So I think the biggest change in obesity medicine is the creation of stopping rules that allow you to say, ‘OK, maybe this isn’t going to work. There’s some other reason you’re gaining weight, so let’s move on to something else,’” Dr. Fujioka said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

“When you stop the medication, you improve the risk-benefit ratio by removing all risk. That’s a win-win to me, and I applaud the FDA for getting on the pharmaceutical companies to make sure they put stopping rules in their medication labels,” he added.

He presented a post hoc pooled analysis of two previously published large, double-blind phase III clinical trials of subcutaneous liraglutide at 3 mg/day (Saxenda) or placebo in combination with a diet and exercise intervention for weight loss: the 3,731-patient SCALE Obesity and Prediabetes trial and the 846-patient SCALE Diabetes trial. In both trials liraglutide was started at a dose of 0.6 mg and titrated to 3.0 mg by week 4. The lifestyle intervention entailed a 500-kcal/day deficit diet and a minimum of 150 minutes of physical activity per week.

The purpose of the pooled analysis was to identify the best early predictor of response status at 56 weeks by examining the impact of 3%, 4%, and 5% weight loss after 8, 12, and 16 weeks of treatment as cut points. This post hoc analysis was prespecified at the request of the Food and Drug Administration before the trials were completed.

The bottom line: The best predictor of long-term outcome on liraglutide, a glucagonlike peptide–1 analog, proved to be a weight loss of 4% or greater at 16 weeks. It had an 81% positive predictive value and a 76% negative predictive value for at least a 5% weight loss at 56 weeks. It correctly predicted weight outcomes at 56 weeks in 80.1% of patients, the highest success rate of all the combinations studied. This finding was the impetus for the current product labeling, which contains the stopping rule. Dr. Fujioka shared study data not included in the labeling; namely, the marked contrast in how early responders and early nonresponders fared at 56 weeks.

The mean weight loss at 56 weeks in nondiabetic early responders to liraglutide was 10.8%, compared with only 3% in early nondiabetic nonresponders. Diabetic early responders averaged an 8.5% weight loss at 56 weeks, while early nonresponders had a mean 3.1% weight loss.

In the SCALE Obesity and Prediabetes trial, 50% of early responders to liraglutide ended up with a greater than 10% weight loss at 56 weeks, and 21% had more than 15% weight loss, compared with rates of 6% and 2%, respectively, in early nonresponders.

In the SCALE Diabetes study, 38% of early responders had greater than 10% weight loss long term, a rate nearly fourfold higher than in early nonresponders. Moreover, 10% of early responder diabetic patients had greater than 15% weight loss, versus a mere 2% of early nonresponders, the internist continued.

The ratio of early responders to early nonresponders in the nondiabetic population was 77%:23%. In diabetic patients, it was 63%:37%.

Turning to cardiometabolic endpoints, Dr. Fujioka noted that early responders in the SCALE Obesity and Prediabetes trial went on to show a mean reduction in systolic blood pressure of 5.1 mm Hg at 56 weeks, compared with a 2–mm Hg decrease in early nonresponders. Early responders also averaged a 10.5-cm shrinkage in waist circumference from a baseline of 115 cm, which was more than twice that observed at 56 weeks in early nonresponders. HDL-cholesterol level rose by 3.9% in early responders but remained unchanged over time in early nonresponders.

Diabetic patients who were early responders to liraglutide 3.0 mg/day had a mean 44.2-mg/dL reduction in fasting plasma glucose at 56 weeks from a baseline of 158 mg/dL, compared with a 30.1-mg/dL decrease in early nonresponders.

“The drop in fasting blood glucose is very quick – within a matter of weeks – so if you already have diabetic patients on drugs that are going to bring their blood sugar down, you may have to back titrate those other drugs really quickly. You don’t want to make your patients hypoglycemic,” the physician said.

Mean hemoglobin A_1c values in early responder diabetic patients fell by 1.6% from a baseline of 7.9%, a full 0.5% greater reduction than in early nonresponders.

By far the most frequent adverse events in the two SCALE trials were gastrointestinal, with nausea leading the way. Rates were modestly higher in the early responders.

 

This analysis and the clinical trials on which it was based were sponsored by Novo Nordisk, which markets liraglutide under the brand names Saxenda and Voctoza. The presenter reported receiving research grants from and serving as a consultant to Novo Nordisk and other pharmaceutical companies.

NEW ORLEANS – Early weight loss on liraglutide – specifically, dropping at least 4% of body weight at 16 weeks – is a strong and clinically useful identifier of patients with a high likelihood of significant weight loss 13 months into treatment, with an accompanying improvement in cardiometabolic risk factors, according to Ken Fujioka, MD.

Conversely, patients who aren’t early responders to subcutaneous liraglutide at 3 mg/day are unlikely to achieve at least 5% weight loss after a full year on the drug, the regulatory benchmark for clinically meaningful weight loss, added Dr. Fujioka, an internist and director of the center for weight management at the Scripps Clinic in La Jolla, Calif.

“Using this early response criterion at week 16 to predict long-term weight loss is to me a very valuable tool. Obesity is an odd disease because it has so many different causes. Finding the right drug is tough, and how long to keep trying with a particular medication is something we haven’t known. So I think the biggest change in obesity medicine is the creation of stopping rules that allow you to say, ‘OK, maybe this isn’t going to work. There’s some other reason you’re gaining weight, so let’s move on to something else,’” Dr. Fujioka said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

“When you stop the medication, you improve the risk-benefit ratio by removing all risk. That’s a win-win to me, and I applaud the FDA for getting on the pharmaceutical companies to make sure they put stopping rules in their medication labels,” he added.

He presented a post hoc pooled analysis of two previously published large, double-blind phase III clinical trials of subcutaneous liraglutide at 3 mg/day (Saxenda) or placebo in combination with a diet and exercise intervention for weight loss: the 3,731-patient SCALE Obesity and Prediabetes trial and the 846-patient SCALE Diabetes trial. In both trials liraglutide was started at a dose of 0.6 mg and titrated to 3.0 mg by week 4. The lifestyle intervention entailed a 500-kcal/day deficit diet and a minimum of 150 minutes of physical activity per week.

The purpose of the pooled analysis was to identify the best early predictor of response status at 56 weeks by examining the impact of 3%, 4%, and 5% weight loss after 8, 12, and 16 weeks of treatment as cut points. This post hoc analysis was prespecified at the request of the Food and Drug Administration before the trials were completed.

The bottom line: The best predictor of long-term outcome on liraglutide, a glucagonlike peptide–1 analog, proved to be a weight loss of 4% or greater at 16 weeks. It had an 81% positive predictive value and a 76% negative predictive value for at least a 5% weight loss at 56 weeks. It correctly predicted weight outcomes at 56 weeks in 80.1% of patients, the highest success rate of all the combinations studied. This finding was the impetus for the current product labeling, which contains the stopping rule. Dr. Fujioka shared study data not included in the labeling; namely, the marked contrast in how early responders and early nonresponders fared at 56 weeks.

The mean weight loss at 56 weeks in nondiabetic early responders to liraglutide was 10.8%, compared with only 3% in early nondiabetic nonresponders. Diabetic early responders averaged an 8.5% weight loss at 56 weeks, while early nonresponders had a mean 3.1% weight loss.

In the SCALE Obesity and Prediabetes trial, 50% of early responders to liraglutide ended up with a greater than 10% weight loss at 56 weeks, and 21% had more than 15% weight loss, compared with rates of 6% and 2%, respectively, in early nonresponders.

In the SCALE Diabetes study, 38% of early responders had greater than 10% weight loss long term, a rate nearly fourfold higher than in early nonresponders. Moreover, 10% of early responder diabetic patients had greater than 15% weight loss, versus a mere 2% of early nonresponders, the internist continued.

The ratio of early responders to early nonresponders in the nondiabetic population was 77%:23%. In diabetic patients, it was 63%:37%.

Turning to cardiometabolic endpoints, Dr. Fujioka noted that early responders in the SCALE Obesity and Prediabetes trial went on to show a mean reduction in systolic blood pressure of 5.1 mm Hg at 56 weeks, compared with a 2–mm Hg decrease in early nonresponders. Early responders also averaged a 10.5-cm shrinkage in waist circumference from a baseline of 115 cm, which was more than twice that observed at 56 weeks in early nonresponders. HDL-cholesterol level rose by 3.9% in early responders but remained unchanged over time in early nonresponders.

Diabetic patients who were early responders to liraglutide 3.0 mg/day had a mean 44.2-mg/dL reduction in fasting plasma glucose at 56 weeks from a baseline of 158 mg/dL, compared with a 30.1-mg/dL decrease in early nonresponders.

“The drop in fasting blood glucose is very quick – within a matter of weeks – so if you already have diabetic patients on drugs that are going to bring their blood sugar down, you may have to back titrate those other drugs really quickly. You don’t want to make your patients hypoglycemic,” the physician said.

Mean hemoglobin A_1c values in early responder diabetic patients fell by 1.6% from a baseline of 7.9%, a full 0.5% greater reduction than in early nonresponders.

By far the most frequent adverse events in the two SCALE trials were gastrointestinal, with nausea leading the way. Rates were modestly higher in the early responders.

 

This analysis and the clinical trials on which it was based were sponsored by Novo Nordisk, which markets liraglutide under the brand names Saxenda and Voctoza. The presenter reported receiving research grants from and serving as a consultant to Novo Nordisk and other pharmaceutical companies.

NEW ORLEANS – Early weight loss on liraglutide – specifically, dropping at least 4% of body weight at 16 weeks – is a strong and clinically useful identifier of patients with a high likelihood of significant weight loss 13 months into treatment, with an accompanying improvement in cardiometabolic risk factors, according to Ken Fujioka, MD.

Conversely, patients who aren’t early responders to subcutaneous liraglutide at 3 mg/day are unlikely to achieve at least 5% weight loss after a full year on the drug, the regulatory benchmark for clinically meaningful weight loss, added Dr. Fujioka, an internist and director of the center for weight management at the Scripps Clinic in La Jolla, Calif.

“Using this early response criterion at week 16 to predict long-term weight loss is to me a very valuable tool. Obesity is an odd disease because it has so many different causes. Finding the right drug is tough, and how long to keep trying with a particular medication is something we haven’t known. So I think the biggest change in obesity medicine is the creation of stopping rules that allow you to say, ‘OK, maybe this isn’t going to work. There’s some other reason you’re gaining weight, so let’s move on to something else,’” Dr. Fujioka said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

“When you stop the medication, you improve the risk-benefit ratio by removing all risk. That’s a win-win to me, and I applaud the FDA for getting on the pharmaceutical companies to make sure they put stopping rules in their medication labels,” he added.

He presented a post hoc pooled analysis of two previously published large, double-blind phase III clinical trials of subcutaneous liraglutide at 3 mg/day (Saxenda) or placebo in combination with a diet and exercise intervention for weight loss: the 3,731-patient SCALE Obesity and Prediabetes trial and the 846-patient SCALE Diabetes trial. In both trials liraglutide was started at a dose of 0.6 mg and titrated to 3.0 mg by week 4. The lifestyle intervention entailed a 500-kcal/day deficit diet and a minimum of 150 minutes of physical activity per week.

The purpose of the pooled analysis was to identify the best early predictor of response status at 56 weeks by examining the impact of 3%, 4%, and 5% weight loss after 8, 12, and 16 weeks of treatment as cut points. This post hoc analysis was prespecified at the request of the Food and Drug Administration before the trials were completed.

The bottom line: The best predictor of long-term outcome on liraglutide, a glucagonlike peptide–1 analog, proved to be a weight loss of 4% or greater at 16 weeks. It had an 81% positive predictive value and a 76% negative predictive value for at least a 5% weight loss at 56 weeks. It correctly predicted weight outcomes at 56 weeks in 80.1% of patients, the highest success rate of all the combinations studied. This finding was the impetus for the current product labeling, which contains the stopping rule. Dr. Fujioka shared study data not included in the labeling; namely, the marked contrast in how early responders and early nonresponders fared at 56 weeks.

The mean weight loss at 56 weeks in nondiabetic early responders to liraglutide was 10.8%, compared with only 3% in early nondiabetic nonresponders. Diabetic early responders averaged an 8.5% weight loss at 56 weeks, while early nonresponders had a mean 3.1% weight loss.

In the SCALE Obesity and Prediabetes trial, 50% of early responders to liraglutide ended up with a greater than 10% weight loss at 56 weeks, and 21% had more than 15% weight loss, compared with rates of 6% and 2%, respectively, in early nonresponders.

In the SCALE Diabetes study, 38% of early responders had greater than 10% weight loss long term, a rate nearly fourfold higher than in early nonresponders. Moreover, 10% of early responder diabetic patients had greater than 15% weight loss, versus a mere 2% of early nonresponders, the internist continued.

The ratio of early responders to early nonresponders in the nondiabetic population was 77%:23%. In diabetic patients, it was 63%:37%.

Turning to cardiometabolic endpoints, Dr. Fujioka noted that early responders in the SCALE Obesity and Prediabetes trial went on to show a mean reduction in systolic blood pressure of 5.1 mm Hg at 56 weeks, compared with a 2–mm Hg decrease in early nonresponders. Early responders also averaged a 10.5-cm shrinkage in waist circumference from a baseline of 115 cm, which was more than twice that observed at 56 weeks in early nonresponders. HDL-cholesterol level rose by 3.9% in early responders but remained unchanged over time in early nonresponders.

Diabetic patients who were early responders to liraglutide 3.0 mg/day had a mean 44.2-mg/dL reduction in fasting plasma glucose at 56 weeks from a baseline of 158 mg/dL, compared with a 30.1-mg/dL decrease in early nonresponders.

“The drop in fasting blood glucose is very quick – within a matter of weeks – so if you already have diabetic patients on drugs that are going to bring their blood sugar down, you may have to back titrate those other drugs really quickly. You don’t want to make your patients hypoglycemic,” the physician said.

Mean hemoglobin A_1c values in early responder diabetic patients fell by 1.6% from a baseline of 7.9%, a full 0.5% greater reduction than in early nonresponders.

By far the most frequent adverse events in the two SCALE trials were gastrointestinal, with nausea leading the way. Rates were modestly higher in the early responders.

 

This analysis and the clinical trials on which it was based were sponsored by Novo Nordisk, which markets liraglutide under the brand names Saxenda and Voctoza. The presenter reported receiving research grants from and serving as a consultant to Novo Nordisk and other pharmaceutical companies.

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
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“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

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The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

[email protected]

The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
[[{"attributes":{},"fields":{}}]]

“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

[[{"attributes":{},"fields":{}}]]

The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

[email protected]

The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
[[{"attributes":{},"fields":{}}]]

“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

[[{"attributes":{},"fields":{}}]]

The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

[email protected]