Mary Ann Moon

A patient’s body mass index before bariatric surgery is unrelated to remission of his or her diabetes afterward, according to a report published online in Annals of Surgery.

In a meta-analysis of 94 observational and interventional clinical studies, the efficacy of the surgery as a metabolic procedure had nothing to do with baseline body mass index (BMI) and instead depended on the degree of diabetic compromise at baseline. “We believe therefore that the use of baseline BMIs to gauge the metabolic effect of surgery is misleading and should be avoided,” said Simona Panunzi, Ph.D., of the Italian National Council of Research-Institute of Systems Analysis and Computer Sciences, Biomathematics Laboratory, Rome, and her associates.

At present, baseline BMI is considered the only valid selection criterion for bariatric surgery in diabetic adults, even though numerous studies have reported that neither BMI nor body weight are good predictors of diabetes remission. In contrast, many other studies have reported that body fat distribution, and visceral obesity in particular, directly affects glycemic control, insulin resistance, and the metabolic syndrome, the investigators commented (Ann. Surg. 2014 Oct. 30 [E-pub ahead of print]).

To assess which factors best predict diabetes remission after bariatric surgery, Dr. Panunzi and her associates performed a systematic review and meta-analysis of the literature. They screened 1,437 articles and focused on 94: 35 studies included patients with a baseline BMI of less than 35 kg/m², 56 studies included patients with a baseline BMI of 35 kg/m² or more, and 3 studies included patients with any baseline BMI. There were a total of 94,579 patients, of whom 4,944 had type 2 diabetes.

The mean age of the study participants was approximately 46 years. Bariatric procedures included sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion, laparoscopic gastric banding, and duodenal-jejunal bypass. Across all the studies, the percent reduction in mean BMI after surgery was 17% for patients with a baseline BMI of less than 35 kg/m² (group 1) and 35% for those with a baseline BMI of 35 kg/m² or more (group 2).

Diabetes remitted in 72% of the patients in group 1 and 71% of those in group 2, a nonsignificant difference. The only factor found to predict remission, defined as the normalization of HbA_1c, was the severity of diabetes as measured by fasting levels of glucose, insulin, and HbA_1c at baseline, the investigators said.

“The appropriateness of the BMI criterion proposed by the National Institutes of Health for determining the eligibility of patients with diabetes for bariatric surgery has already been challenged by other authors. However, until now there was no direct evidence of its lack of relevance. It seems clear from the results of [our] study that baseline BMI does not carry prognostic information for diabetes resolution after bariatric surgery,” they added.

This meta-analysis was limited in that few of the reviewed studies reported diabetes duration, a well-known predictor of remission. And the definition of diabetes remission varied widely among the studies, from simple withdrawal of diabetes medications to various specific plasma glucose or HbA_1c levels, the investigators noted.

A patient’s body mass index before bariatric surgery is unrelated to remission of his or her diabetes afterward, according to a report published online in Annals of Surgery.

In a meta-analysis of 94 observational and interventional clinical studies, the efficacy of the surgery as a metabolic procedure had nothing to do with baseline body mass index (BMI) and instead depended on the degree of diabetic compromise at baseline. “We believe therefore that the use of baseline BMIs to gauge the metabolic effect of surgery is misleading and should be avoided,” said Simona Panunzi, Ph.D., of the Italian National Council of Research-Institute of Systems Analysis and Computer Sciences, Biomathematics Laboratory, Rome, and her associates.

At present, baseline BMI is considered the only valid selection criterion for bariatric surgery in diabetic adults, even though numerous studies have reported that neither BMI nor body weight are good predictors of diabetes remission. In contrast, many other studies have reported that body fat distribution, and visceral obesity in particular, directly affects glycemic control, insulin resistance, and the metabolic syndrome, the investigators commented (Ann. Surg. 2014 Oct. 30 [E-pub ahead of print]).

To assess which factors best predict diabetes remission after bariatric surgery, Dr. Panunzi and her associates performed a systematic review and meta-analysis of the literature. They screened 1,437 articles and focused on 94: 35 studies included patients with a baseline BMI of less than 35 kg/m², 56 studies included patients with a baseline BMI of 35 kg/m² or more, and 3 studies included patients with any baseline BMI. There were a total of 94,579 patients, of whom 4,944 had type 2 diabetes.

The mean age of the study participants was approximately 46 years. Bariatric procedures included sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion, laparoscopic gastric banding, and duodenal-jejunal bypass. Across all the studies, the percent reduction in mean BMI after surgery was 17% for patients with a baseline BMI of less than 35 kg/m² (group 1) and 35% for those with a baseline BMI of 35 kg/m² or more (group 2).

Diabetes remitted in 72% of the patients in group 1 and 71% of those in group 2, a nonsignificant difference. The only factor found to predict remission, defined as the normalization of HbA_1c, was the severity of diabetes as measured by fasting levels of glucose, insulin, and HbA_1c at baseline, the investigators said.

“The appropriateness of the BMI criterion proposed by the National Institutes of Health for determining the eligibility of patients with diabetes for bariatric surgery has already been challenged by other authors. However, until now there was no direct evidence of its lack of relevance. It seems clear from the results of [our] study that baseline BMI does not carry prognostic information for diabetes resolution after bariatric surgery,” they added.

This meta-analysis was limited in that few of the reviewed studies reported diabetes duration, a well-known predictor of remission. And the definition of diabetes remission varied widely among the studies, from simple withdrawal of diabetes medications to various specific plasma glucose or HbA_1c levels, the investigators noted.

A patient’s body mass index before bariatric surgery is unrelated to remission of his or her diabetes afterward, according to a report published online in Annals of Surgery.

In a meta-analysis of 94 observational and interventional clinical studies, the efficacy of the surgery as a metabolic procedure had nothing to do with baseline body mass index (BMI) and instead depended on the degree of diabetic compromise at baseline. “We believe therefore that the use of baseline BMIs to gauge the metabolic effect of surgery is misleading and should be avoided,” said Simona Panunzi, Ph.D., of the Italian National Council of Research-Institute of Systems Analysis and Computer Sciences, Biomathematics Laboratory, Rome, and her associates.

At present, baseline BMI is considered the only valid selection criterion for bariatric surgery in diabetic adults, even though numerous studies have reported that neither BMI nor body weight are good predictors of diabetes remission. In contrast, many other studies have reported that body fat distribution, and visceral obesity in particular, directly affects glycemic control, insulin resistance, and the metabolic syndrome, the investigators commented (Ann. Surg. 2014 Oct. 30 [E-pub ahead of print]).

To assess which factors best predict diabetes remission after bariatric surgery, Dr. Panunzi and her associates performed a systematic review and meta-analysis of the literature. They screened 1,437 articles and focused on 94: 35 studies included patients with a baseline BMI of less than 35 kg/m², 56 studies included patients with a baseline BMI of 35 kg/m² or more, and 3 studies included patients with any baseline BMI. There were a total of 94,579 patients, of whom 4,944 had type 2 diabetes.

The mean age of the study participants was approximately 46 years. Bariatric procedures included sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion, laparoscopic gastric banding, and duodenal-jejunal bypass. Across all the studies, the percent reduction in mean BMI after surgery was 17% for patients with a baseline BMI of less than 35 kg/m² (group 1) and 35% for those with a baseline BMI of 35 kg/m² or more (group 2).

Diabetes remitted in 72% of the patients in group 1 and 71% of those in group 2, a nonsignificant difference. The only factor found to predict remission, defined as the normalization of HbA_1c, was the severity of diabetes as measured by fasting levels of glucose, insulin, and HbA_1c at baseline, the investigators said.

“The appropriateness of the BMI criterion proposed by the National Institutes of Health for determining the eligibility of patients with diabetes for bariatric surgery has already been challenged by other authors. However, until now there was no direct evidence of its lack of relevance. It seems clear from the results of [our] study that baseline BMI does not carry prognostic information for diabetes resolution after bariatric surgery,” they added.

This meta-analysis was limited in that few of the reviewed studies reported diabetes duration, a well-known predictor of remission. And the definition of diabetes remission varied widely among the studies, from simple withdrawal of diabetes medications to various specific plasma glucose or HbA_1c levels, the investigators noted.

Differences in circulating biomarkers distinguished blunt trauma patients who improved over time from those who instead developed serial persistent infections and multiple organ failures in a single-center retrospective cohort study published online in Annals of Surgery.

The distinctly different patterns in biomarkers were already becoming apparent in blood samples taken at admission to the ICU, and they evolved over the first week of hospitalization. The patterns in patients who went on to develop infections and organ failures most likely reflect an excessive inflammatory response to injury, which caused further immune dysregulation and impairment of host physiological function that rendered patients susceptible to severe infection.

“We propose that a combination of traditional parameters of inflammation, such as white blood cell differential, combined with a novel subset of circulating biomarkers measured upon presentation and over the initial 24 hours, could be used to stratify ICU patients for either more or less intensive care and monitoring,” wrote the investigators. This would optimize both resource utilization and patient outcomes, wrote the investigators, led by Dr. Rami A. Namas of the department of surgery and Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh (Ann. Surg. 2014 Nov. 3).

They analyzed blood test results from 472 adults who survived severe blunt trauma and were admitted to the emergency department of a trauma center during an 8-year period. A total of 127 (27%) went on to develop persistent nosocomial infections – including 79 cases of pneumonia, 39 of urinary tract infections, 15 of bloodstream infections, 5 of wound infections, 2 of empyema, and 1 of Clostridium difficile infection – and organ failure. The study participants had undergone blood sampling via central venous or arterial catheters at least three times during the first 24 hours in the ICU, as well as at frequent intervals for at least a week. Samples were tested for the levels of 26 inflammatory biomarkers.

The investigators then performed a case-control analysis differentiating the blood test results between a subgroup of 44 patients who never developed nosocomial infections from 44 who had. They excluded patients who received blood transfusions or underwent emergency surgery within the first 24 hours, “to avoid the confounding impact of these interventions on the overall inflammatory response.” They also selected only patients whose trauma was caused by a motor vehicle accident, to avoid confounding factors related to the mechanism of injury. The two study groups were rigorously matched for patient age, patient sex, and Injury Severity Score.

Overall, injury severity was comparable between the two study groups. The severity of brain injury in particular, as reflected in Glasgow Coma Scores, was not significantly worse for patients who developed persistent infections. Both groups also showed a virtually identical pattern of elevation in the chemokines MIG/CXCL9, IL-8/CXCL8, and eotaxins, beginning at admission and continuing throughout the first week of ICU care. This suggests that these mediators are a component of a normal immune response to injury.

However, patients who developed persistent infections had “larger and more highly connected networks of systemic inflammation biomarkers” than did the other patients, suggesting that “mounting an adequately robust inflammatory response is essential for effective restoration of homeostasis after injury, [but] an overly exuberant and sustained immune response may be detrimental,” the investigators said.

At admission, the patients who later developed persistent infections had much higher levels than did the patients who recovered of the biomarkers IL-6, MCP-1/CCL2, HMGB1, and IL-1RA. “The early peak suggests that these mediators are produced in response to preexisting factors or variables associated with injury mechanism/pattern or prehospital management that are not revealed in our analysis. It is unclear, for example, if this pattern reflects the higher incidence of thoracic trauma in the [persistent infection] group,” Dr. Namas and his associates wrote.

After 12 hours, this pattern of biomarkers gave way to an increase in cytokines either produced by lymphoid cells or involved in the regulation of lymphocyte responses. This relatively early engagement of the lymphocyte response correlated with the development of multiple organ dysfunction beginning on day 2, which progressed over time in the infection group but rapidly resolved in the group that had an uncomplicated recovery. “We speculate that the gradual elevations of cytokines such as IL-1beta and TNF-alpha ... could reflect the response to microbes in the early phases of infection, though further studies are needed to test this hypothesis,” the researchers said. Compared with the patients who recovered, those who developed persistent infections also showed significant elevations in total leukocyte counts and polymorphonuclear neutrophils percentage, beginning at admission and continuing throughout the first week. They showed sustained lymphopenia from admission through 2 weeks of ICU care. This suggests that lymphocyte depletion “plays a detrimental role in the evolution of nosocomial sepsis-induced multiple organ failure after traumatic injury,” they noted.

Differences in circulating biomarkers distinguished blunt trauma patients who improved over time from those who instead developed serial persistent infections and multiple organ failures in a single-center retrospective cohort study published online in Annals of Surgery.

The distinctly different patterns in biomarkers were already becoming apparent in blood samples taken at admission to the ICU, and they evolved over the first week of hospitalization. The patterns in patients who went on to develop infections and organ failures most likely reflect an excessive inflammatory response to injury, which caused further immune dysregulation and impairment of host physiological function that rendered patients susceptible to severe infection.

“We propose that a combination of traditional parameters of inflammation, such as white blood cell differential, combined with a novel subset of circulating biomarkers measured upon presentation and over the initial 24 hours, could be used to stratify ICU patients for either more or less intensive care and monitoring,” wrote the investigators. This would optimize both resource utilization and patient outcomes, wrote the investigators, led by Dr. Rami A. Namas of the department of surgery and Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh (Ann. Surg. 2014 Nov. 3).

They analyzed blood test results from 472 adults who survived severe blunt trauma and were admitted to the emergency department of a trauma center during an 8-year period. A total of 127 (27%) went on to develop persistent nosocomial infections – including 79 cases of pneumonia, 39 of urinary tract infections, 15 of bloodstream infections, 5 of wound infections, 2 of empyema, and 1 of Clostridium difficile infection – and organ failure. The study participants had undergone blood sampling via central venous or arterial catheters at least three times during the first 24 hours in the ICU, as well as at frequent intervals for at least a week. Samples were tested for the levels of 26 inflammatory biomarkers.

The investigators then performed a case-control analysis differentiating the blood test results between a subgroup of 44 patients who never developed nosocomial infections from 44 who had. They excluded patients who received blood transfusions or underwent emergency surgery within the first 24 hours, “to avoid the confounding impact of these interventions on the overall inflammatory response.” They also selected only patients whose trauma was caused by a motor vehicle accident, to avoid confounding factors related to the mechanism of injury. The two study groups were rigorously matched for patient age, patient sex, and Injury Severity Score.

Overall, injury severity was comparable between the two study groups. The severity of brain injury in particular, as reflected in Glasgow Coma Scores, was not significantly worse for patients who developed persistent infections. Both groups also showed a virtually identical pattern of elevation in the chemokines MIG/CXCL9, IL-8/CXCL8, and eotaxins, beginning at admission and continuing throughout the first week of ICU care. This suggests that these mediators are a component of a normal immune response to injury.

However, patients who developed persistent infections had “larger and more highly connected networks of systemic inflammation biomarkers” than did the other patients, suggesting that “mounting an adequately robust inflammatory response is essential for effective restoration of homeostasis after injury, [but] an overly exuberant and sustained immune response may be detrimental,” the investigators said.

At admission, the patients who later developed persistent infections had much higher levels than did the patients who recovered of the biomarkers IL-6, MCP-1/CCL2, HMGB1, and IL-1RA. “The early peak suggests that these mediators are produced in response to preexisting factors or variables associated with injury mechanism/pattern or prehospital management that are not revealed in our analysis. It is unclear, for example, if this pattern reflects the higher incidence of thoracic trauma in the [persistent infection] group,” Dr. Namas and his associates wrote.

After 12 hours, this pattern of biomarkers gave way to an increase in cytokines either produced by lymphoid cells or involved in the regulation of lymphocyte responses. This relatively early engagement of the lymphocyte response correlated with the development of multiple organ dysfunction beginning on day 2, which progressed over time in the infection group but rapidly resolved in the group that had an uncomplicated recovery. “We speculate that the gradual elevations of cytokines such as IL-1beta and TNF-alpha ... could reflect the response to microbes in the early phases of infection, though further studies are needed to test this hypothesis,” the researchers said. Compared with the patients who recovered, those who developed persistent infections also showed significant elevations in total leukocyte counts and polymorphonuclear neutrophils percentage, beginning at admission and continuing throughout the first week. They showed sustained lymphopenia from admission through 2 weeks of ICU care. This suggests that lymphocyte depletion “plays a detrimental role in the evolution of nosocomial sepsis-induced multiple organ failure after traumatic injury,” they noted.

Differences in circulating biomarkers distinguished blunt trauma patients who improved over time from those who instead developed serial persistent infections and multiple organ failures in a single-center retrospective cohort study published online in Annals of Surgery.

The distinctly different patterns in biomarkers were already becoming apparent in blood samples taken at admission to the ICU, and they evolved over the first week of hospitalization. The patterns in patients who went on to develop infections and organ failures most likely reflect an excessive inflammatory response to injury, which caused further immune dysregulation and impairment of host physiological function that rendered patients susceptible to severe infection.

“We propose that a combination of traditional parameters of inflammation, such as white blood cell differential, combined with a novel subset of circulating biomarkers measured upon presentation and over the initial 24 hours, could be used to stratify ICU patients for either more or less intensive care and monitoring,” wrote the investigators. This would optimize both resource utilization and patient outcomes, wrote the investigators, led by Dr. Rami A. Namas of the department of surgery and Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh (Ann. Surg. 2014 Nov. 3).

They analyzed blood test results from 472 adults who survived severe blunt trauma and were admitted to the emergency department of a trauma center during an 8-year period. A total of 127 (27%) went on to develop persistent nosocomial infections – including 79 cases of pneumonia, 39 of urinary tract infections, 15 of bloodstream infections, 5 of wound infections, 2 of empyema, and 1 of Clostridium difficile infection – and organ failure. The study participants had undergone blood sampling via central venous or arterial catheters at least three times during the first 24 hours in the ICU, as well as at frequent intervals for at least a week. Samples were tested for the levels of 26 inflammatory biomarkers.

The investigators then performed a case-control analysis differentiating the blood test results between a subgroup of 44 patients who never developed nosocomial infections from 44 who had. They excluded patients who received blood transfusions or underwent emergency surgery within the first 24 hours, “to avoid the confounding impact of these interventions on the overall inflammatory response.” They also selected only patients whose trauma was caused by a motor vehicle accident, to avoid confounding factors related to the mechanism of injury. The two study groups were rigorously matched for patient age, patient sex, and Injury Severity Score.

Overall, injury severity was comparable between the two study groups. The severity of brain injury in particular, as reflected in Glasgow Coma Scores, was not significantly worse for patients who developed persistent infections. Both groups also showed a virtually identical pattern of elevation in the chemokines MIG/CXCL9, IL-8/CXCL8, and eotaxins, beginning at admission and continuing throughout the first week of ICU care. This suggests that these mediators are a component of a normal immune response to injury.

However, patients who developed persistent infections had “larger and more highly connected networks of systemic inflammation biomarkers” than did the other patients, suggesting that “mounting an adequately robust inflammatory response is essential for effective restoration of homeostasis after injury, [but] an overly exuberant and sustained immune response may be detrimental,” the investigators said.

At admission, the patients who later developed persistent infections had much higher levels than did the patients who recovered of the biomarkers IL-6, MCP-1/CCL2, HMGB1, and IL-1RA. “The early peak suggests that these mediators are produced in response to preexisting factors or variables associated with injury mechanism/pattern or prehospital management that are not revealed in our analysis. It is unclear, for example, if this pattern reflects the higher incidence of thoracic trauma in the [persistent infection] group,” Dr. Namas and his associates wrote.

After 12 hours, this pattern of biomarkers gave way to an increase in cytokines either produced by lymphoid cells or involved in the regulation of lymphocyte responses. This relatively early engagement of the lymphocyte response correlated with the development of multiple organ dysfunction beginning on day 2, which progressed over time in the infection group but rapidly resolved in the group that had an uncomplicated recovery. “We speculate that the gradual elevations of cytokines such as IL-1beta and TNF-alpha ... could reflect the response to microbes in the early phases of infection, though further studies are needed to test this hypothesis,” the researchers said. Compared with the patients who recovered, those who developed persistent infections also showed significant elevations in total leukocyte counts and polymorphonuclear neutrophils percentage, beginning at admission and continuing throughout the first week. They showed sustained lymphopenia from admission through 2 weeks of ICU care. This suggests that lymphocyte depletion “plays a detrimental role in the evolution of nosocomial sepsis-induced multiple organ failure after traumatic injury,” they noted.

Receiving the Tdap vaccine during pregnancy did not raise the risk of maternal hypertensive disorders, preterm birth, or small-for-gestational age infants in an observational study of 123,494 California pregnancies, according to a report published online November 11 in JAMA.

In response to recent outbreaks of pertussis, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends that the Tdap vaccine be given to all pregnant women, preferably at 27-36 weeks’ gestation. However, specific data regarding possible adverse effects on mothers or children are “limited,” said Dr. Elyse O. Kharbanda of HealthPartners Institute for Education and Research, Minneapolis, and her associates.

To examine the issue, the investigators analyzed information from the Vaccine Safety Datalink regarding singleton pregnancies resulting in a live birth at two California sites during a 3-year period. A total of 26,229 (21%) of mothers received the Tdap vaccine during pregnancy, and the remaining 97,265 did not, although 46% of them had received Tdap prior to pregnancy.

© AvailableLight / stockphoto.com

The rates of preterm birth were 6.3% in vaccine-exposed pregnancies and 7.8% in nonexposed pregnancies, a nonsignificant difference. Similarly, the rates of SGA infants were nearly identical between the two study groups at 8.4% and 8.3%, respectively. And the rates of maternal hypertensive disorders – including gestational hypertension, hypertension in pregnancy not otherwise specified, preeclampsia, and eclampsia – were not significantly different at 8.2% and 8.0%, respectively, Dr. Kharbanda and her associates said (JAMA 2014 [doi:10.1001/jama.2014.14825]).

“We detected an increased risk of being diagnosed with chorioamnionitis following vaccination,” but that finding should be interpreted with caution because the magnitude of the risk was small, and it didn’t translate into increased risk of preterm delivery. This weak association may have been due to residual confounding, especially since the data could not be adjusted to account for important chorioamnionitis risk factors such as prolonged rupture of membranes, prolonged labor, or the presence of pathogens in the mother’s genital tract, the investigators noted.

This study was funded by the Centers for Disease Control and Prevention. Dr. Kharbanda reported having no financial disclosures; some of her associates reported ties to GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Novartis, Nuron Biotech, Protein Science, and MedImmune. Two associates are CDC employees.

Receiving the Tdap vaccine during pregnancy did not raise the risk of maternal hypertensive disorders, preterm birth, or small-for-gestational age infants in an observational study of 123,494 California pregnancies, according to a report published online November 11 in JAMA.

In response to recent outbreaks of pertussis, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends that the Tdap vaccine be given to all pregnant women, preferably at 27-36 weeks’ gestation. However, specific data regarding possible adverse effects on mothers or children are “limited,” said Dr. Elyse O. Kharbanda of HealthPartners Institute for Education and Research, Minneapolis, and her associates.

To examine the issue, the investigators analyzed information from the Vaccine Safety Datalink regarding singleton pregnancies resulting in a live birth at two California sites during a 3-year period. A total of 26,229 (21%) of mothers received the Tdap vaccine during pregnancy, and the remaining 97,265 did not, although 46% of them had received Tdap prior to pregnancy.

© AvailableLight / stockphoto.com

The rates of preterm birth were 6.3% in vaccine-exposed pregnancies and 7.8% in nonexposed pregnancies, a nonsignificant difference. Similarly, the rates of SGA infants were nearly identical between the two study groups at 8.4% and 8.3%, respectively. And the rates of maternal hypertensive disorders – including gestational hypertension, hypertension in pregnancy not otherwise specified, preeclampsia, and eclampsia – were not significantly different at 8.2% and 8.0%, respectively, Dr. Kharbanda and her associates said (JAMA 2014 [doi:10.1001/jama.2014.14825]).

“We detected an increased risk of being diagnosed with chorioamnionitis following vaccination,” but that finding should be interpreted with caution because the magnitude of the risk was small, and it didn’t translate into increased risk of preterm delivery. This weak association may have been due to residual confounding, especially since the data could not be adjusted to account for important chorioamnionitis risk factors such as prolonged rupture of membranes, prolonged labor, or the presence of pathogens in the mother’s genital tract, the investigators noted.

This study was funded by the Centers for Disease Control and Prevention. Dr. Kharbanda reported having no financial disclosures; some of her associates reported ties to GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Novartis, Nuron Biotech, Protein Science, and MedImmune. Two associates are CDC employees.

Receiving the Tdap vaccine during pregnancy did not raise the risk of maternal hypertensive disorders, preterm birth, or small-for-gestational age infants in an observational study of 123,494 California pregnancies, according to a report published online November 11 in JAMA.

In response to recent outbreaks of pertussis, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends that the Tdap vaccine be given to all pregnant women, preferably at 27-36 weeks’ gestation. However, specific data regarding possible adverse effects on mothers or children are “limited,” said Dr. Elyse O. Kharbanda of HealthPartners Institute for Education and Research, Minneapolis, and her associates.

To examine the issue, the investigators analyzed information from the Vaccine Safety Datalink regarding singleton pregnancies resulting in a live birth at two California sites during a 3-year period. A total of 26,229 (21%) of mothers received the Tdap vaccine during pregnancy, and the remaining 97,265 did not, although 46% of them had received Tdap prior to pregnancy.

© AvailableLight / stockphoto.com

The rates of preterm birth were 6.3% in vaccine-exposed pregnancies and 7.8% in nonexposed pregnancies, a nonsignificant difference. Similarly, the rates of SGA infants were nearly identical between the two study groups at 8.4% and 8.3%, respectively. And the rates of maternal hypertensive disorders – including gestational hypertension, hypertension in pregnancy not otherwise specified, preeclampsia, and eclampsia – were not significantly different at 8.2% and 8.0%, respectively, Dr. Kharbanda and her associates said (JAMA 2014 [doi:10.1001/jama.2014.14825]).

“We detected an increased risk of being diagnosed with chorioamnionitis following vaccination,” but that finding should be interpreted with caution because the magnitude of the risk was small, and it didn’t translate into increased risk of preterm delivery. This weak association may have been due to residual confounding, especially since the data could not be adjusted to account for important chorioamnionitis risk factors such as prolonged rupture of membranes, prolonged labor, or the presence of pathogens in the mother’s genital tract, the investigators noted.

This study was funded by the Centers for Disease Control and Prevention. Dr. Kharbanda reported having no financial disclosures; some of her associates reported ties to GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Novartis, Nuron Biotech, Protein Science, and MedImmune. Two associates are CDC employees.

Patients with chronic hepatitis C viral infection and cirrhosis can achieve a normal life expectancy if they attain a sustained virologic response with interferon-based antiviral therapy, according to a Research Letter published online Nov. 11 in JAMA.

Researchers performed a secondary analysis of data from a previous study involving consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis who initiated interferon during 1990-2003 at five large hepatology centers in Europe and Canada. A subgroup of 530 of these study participants was followed for a median of 8 years after completing the treatment, said Adriaan J. van der Meer, M.D., Ph.D., of the department of gastroenterology and hepatology, Erasmus University Medical Center, Rotterdam, and his associates.

The median patient age at baseline was 48 years. A total of 192 patients (36%) attained SVR.

Thirteen patients with SVR died during follow-up, yielding a cumulative 10-year overall survival of 91.1%. This did not differ significantly from survival in the age- and sex-matched general population, despite the study participants’ severe illness, the investigators reported (JAMA 2014;312:1927-8).

In contrast, 100 patients without SVR died during follow-up, for a cumulative 10-year survival of 74.0%. This was significantly lower than survival in the age- and sex-matched general population.

The “excellent” survival benefit of SVR for patients with advanced liver disease might be attributable to regression of hepatic inflammation and fibrosis; reduction of the hepatic venous pressure gradient; a decrease in the rate of hepatocellular carcinoma and liver failure; and a decreased incidence of diabetes, end-stage renal disease, and cardiovascular events, Dr. van der Meer and his associates said.

This study was funded by the Foundation for Liver and Gastrointestinal Research in Rotterdam. Dr. van der Meer reported having received compensation for previous work from Merck Sharp & Dohme and Gilead, and his associates reported ties to numerous industry sources.

Patients with chronic hepatitis C viral infection and cirrhosis can achieve a normal life expectancy if they attain a sustained virologic response with interferon-based antiviral therapy, according to a Research Letter published online Nov. 11 in JAMA.

Researchers performed a secondary analysis of data from a previous study involving consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis who initiated interferon during 1990-2003 at five large hepatology centers in Europe and Canada. A subgroup of 530 of these study participants was followed for a median of 8 years after completing the treatment, said Adriaan J. van der Meer, M.D., Ph.D., of the department of gastroenterology and hepatology, Erasmus University Medical Center, Rotterdam, and his associates.

The median patient age at baseline was 48 years. A total of 192 patients (36%) attained SVR.

Thirteen patients with SVR died during follow-up, yielding a cumulative 10-year overall survival of 91.1%. This did not differ significantly from survival in the age- and sex-matched general population, despite the study participants’ severe illness, the investigators reported (JAMA 2014;312:1927-8).

In contrast, 100 patients without SVR died during follow-up, for a cumulative 10-year survival of 74.0%. This was significantly lower than survival in the age- and sex-matched general population.

The “excellent” survival benefit of SVR for patients with advanced liver disease might be attributable to regression of hepatic inflammation and fibrosis; reduction of the hepatic venous pressure gradient; a decrease in the rate of hepatocellular carcinoma and liver failure; and a decreased incidence of diabetes, end-stage renal disease, and cardiovascular events, Dr. van der Meer and his associates said.

This study was funded by the Foundation for Liver and Gastrointestinal Research in Rotterdam. Dr. van der Meer reported having received compensation for previous work from Merck Sharp & Dohme and Gilead, and his associates reported ties to numerous industry sources.

Patients with chronic hepatitis C viral infection and cirrhosis can achieve a normal life expectancy if they attain a sustained virologic response with interferon-based antiviral therapy, according to a Research Letter published online Nov. 11 in JAMA.

Researchers performed a secondary analysis of data from a previous study involving consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis who initiated interferon during 1990-2003 at five large hepatology centers in Europe and Canada. A subgroup of 530 of these study participants was followed for a median of 8 years after completing the treatment, said Adriaan J. van der Meer, M.D., Ph.D., of the department of gastroenterology and hepatology, Erasmus University Medical Center, Rotterdam, and his associates.

The median patient age at baseline was 48 years. A total of 192 patients (36%) attained SVR.

Thirteen patients with SVR died during follow-up, yielding a cumulative 10-year overall survival of 91.1%. This did not differ significantly from survival in the age- and sex-matched general population, despite the study participants’ severe illness, the investigators reported (JAMA 2014;312:1927-8).

In contrast, 100 patients without SVR died during follow-up, for a cumulative 10-year survival of 74.0%. This was significantly lower than survival in the age- and sex-matched general population.

The “excellent” survival benefit of SVR for patients with advanced liver disease might be attributable to regression of hepatic inflammation and fibrosis; reduction of the hepatic venous pressure gradient; a decrease in the rate of hepatocellular carcinoma and liver failure; and a decreased incidence of diabetes, end-stage renal disease, and cardiovascular events, Dr. van der Meer and his associates said.

This study was funded by the Foundation for Liver and Gastrointestinal Research in Rotterdam. Dr. van der Meer reported having received compensation for previous work from Merck Sharp & Dohme and Gilead, and his associates reported ties to numerous industry sources.

An oral, interferon-free drug regimen produced a 97% rate of sustained virologic response in liver transplant recipients who had recurrent hepatitis C viral infection – “an historically difficult-to-treat population” at high risk of death who have extremely limited treatment options, according to a study reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an industry-sponsored, open-label phase II trial involving 34 adults with recurrent HCV infection following liver transplantation, 24 weeks of daily ombitasvir plus the ritonavir-boosted protease inhibitor ABT-450 (ABT-50/r), added to dasabuvir and ribavirin, eradicated every patient’s HCV RNA levels within 4 months. Only one patient had a relapse during a further 24 weeks of follow-up, said Dr. Parvez Mantry of the Liver Institute at Methodist Dallas, who presented the data at the meeting.*

Results of the study, which was conducted at 10 transplant centers in the United States and Spain, were presented at the meeting and simultaneously published online Nov. 11 in the New England Journal of Medicine (N. Engl. J. Med. 2014 Nov. 11 [doi: 10.1056/NEJMoa1408921]).

The standard of care for treating recurrent HCV infection after liver transplantation has been 48 weeks of peginterferon with ribavirin, but response rates are relatively low (13%-43%) because of interferon’s toxic effects. Moreover, the agent is known to induce graft injury, reducing both graft and patient survival.

The investigators assessed the safety and efficacy of a tablet formulation combining ombitasvir, a potent NS5A inhibitor, with ABT-50/r, a protease inhibitor that increases peak, trough, and overall drug exposure and allows once-daily dosing. To this was added standard dasabuvir and ribavirin, with ribavirin dosing adjusted according to the treating physician’s discretion to avert adverse hematologic effects in these immunosuppressed transplant recipients. Modified doses of standard calcineurin inhibitors (cyclosporine or tacrolimus) also were recommended for all patients, and low-dose glucocorticoids were permitted as needed.

The study participants were 18-70 years of age (mean age, 59.6 years) and had received liver transplants because of chronic HCV infection a minimum of 1 year previously. They had no or only mild liver fibrosis, were receiving stable cyclosporine- or tacrolimus-based immunosuppression, and were not coinfected with HIV or hepatitis B.

The primary efficacy endpoint was a sustained virologic response (SVR) 12 weeks after treatment was completed. All the study participants achieved an SVR by week 4 of treatment, which persisted in all of them until treatment was completed. At that time, 1 patient relapsed, so the overall SVR rate was 97%. This same SVR rate was sustained through final follow-up at post-treatment week 24.

In the patient who relapsed, HCV DNA showed resistance-associated genetic variants that had not been present at baseline. This patient also had been unresponsive to previous peginterferon-ribavirin therapy.

Adverse events were common, although the majority were mild or moderate in severity. Fatigue, headache, and cough were the most frequent adverse events. Grade 2 elevations in total bilirubin developed in two patients (6%), with no jaundice or scleral icterus. Nine patients showed grade 2 decreases in hemoglobin; none required a blood transfusion, and five required erythropoietin. There were no deaths and no cases of graft rejection.

One patient discontinued the study drug at week 18 after developing moderate rash, memory impairment, and anxiety deemed to be possibly drug related. However, that patient had already achieved an SVR before discontinuing treatment, and that SVR persisted at final follow-up 12 weeks later.

However, this study was not large enough to allow adequate assessment of adverse event rates or comparison of them with rates for other treatments, the investigators noted.

The researchers also noted that these study participants were easier to treat than the general population of liver transplant recipients with recurrent HCV, because they did not have advanced fibrosis or comorbid infections. In addition, patients with early, aggressive forms of recurrent HCV, such as fibrosing cholestatic hepatitis, were excluded from this study, as were patients maintained on immunosuppressive agents other than cyclosporine or tacrolimus.

This trial was sponsored by AbbVie, whose employees also designed the study, gathered and analyzed the data, and wrote the report. Study investigator Dr. Paul Y. Kwo reported receiving personal fees and grants from, and serving on advisory boards for, AbbVie, Bristol-Myers Squibb, and other companies. His associates reported ties to numerous industry sources.

AGA Resource:

HCV Clinical Service Line: http://www.gastro.org/practice/clinical-service-line/hcv-clinical-service-line

An oral, interferon-free drug regimen produced a 97% rate of sustained virologic response in liver transplant recipients who had recurrent hepatitis C viral infection – “an historically difficult-to-treat population” at high risk of death who have extremely limited treatment options, according to a study reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an industry-sponsored, open-label phase II trial involving 34 adults with recurrent HCV infection following liver transplantation, 24 weeks of daily ombitasvir plus the ritonavir-boosted protease inhibitor ABT-450 (ABT-50/r), added to dasabuvir and ribavirin, eradicated every patient’s HCV RNA levels within 4 months. Only one patient had a relapse during a further 24 weeks of follow-up, said Dr. Parvez Mantry of the Liver Institute at Methodist Dallas, who presented the data at the meeting.*

Results of the study, which was conducted at 10 transplant centers in the United States and Spain, were presented at the meeting and simultaneously published online Nov. 11 in the New England Journal of Medicine (N. Engl. J. Med. 2014 Nov. 11 [doi: 10.1056/NEJMoa1408921]).

The standard of care for treating recurrent HCV infection after liver transplantation has been 48 weeks of peginterferon with ribavirin, but response rates are relatively low (13%-43%) because of interferon’s toxic effects. Moreover, the agent is known to induce graft injury, reducing both graft and patient survival.

The investigators assessed the safety and efficacy of a tablet formulation combining ombitasvir, a potent NS5A inhibitor, with ABT-50/r, a protease inhibitor that increases peak, trough, and overall drug exposure and allows once-daily dosing. To this was added standard dasabuvir and ribavirin, with ribavirin dosing adjusted according to the treating physician’s discretion to avert adverse hematologic effects in these immunosuppressed transplant recipients. Modified doses of standard calcineurin inhibitors (cyclosporine or tacrolimus) also were recommended for all patients, and low-dose glucocorticoids were permitted as needed.

The study participants were 18-70 years of age (mean age, 59.6 years) and had received liver transplants because of chronic HCV infection a minimum of 1 year previously. They had no or only mild liver fibrosis, were receiving stable cyclosporine- or tacrolimus-based immunosuppression, and were not coinfected with HIV or hepatitis B.

The primary efficacy endpoint was a sustained virologic response (SVR) 12 weeks after treatment was completed. All the study participants achieved an SVR by week 4 of treatment, which persisted in all of them until treatment was completed. At that time, 1 patient relapsed, so the overall SVR rate was 97%. This same SVR rate was sustained through final follow-up at post-treatment week 24.

In the patient who relapsed, HCV DNA showed resistance-associated genetic variants that had not been present at baseline. This patient also had been unresponsive to previous peginterferon-ribavirin therapy.

Adverse events were common, although the majority were mild or moderate in severity. Fatigue, headache, and cough were the most frequent adverse events. Grade 2 elevations in total bilirubin developed in two patients (6%), with no jaundice or scleral icterus. Nine patients showed grade 2 decreases in hemoglobin; none required a blood transfusion, and five required erythropoietin. There were no deaths and no cases of graft rejection.

One patient discontinued the study drug at week 18 after developing moderate rash, memory impairment, and anxiety deemed to be possibly drug related. However, that patient had already achieved an SVR before discontinuing treatment, and that SVR persisted at final follow-up 12 weeks later.

However, this study was not large enough to allow adequate assessment of adverse event rates or comparison of them with rates for other treatments, the investigators noted.

The researchers also noted that these study participants were easier to treat than the general population of liver transplant recipients with recurrent HCV, because they did not have advanced fibrosis or comorbid infections. In addition, patients with early, aggressive forms of recurrent HCV, such as fibrosing cholestatic hepatitis, were excluded from this study, as were patients maintained on immunosuppressive agents other than cyclosporine or tacrolimus.

This trial was sponsored by AbbVie, whose employees also designed the study, gathered and analyzed the data, and wrote the report. Study investigator Dr. Paul Y. Kwo reported receiving personal fees and grants from, and serving on advisory boards for, AbbVie, Bristol-Myers Squibb, and other companies. His associates reported ties to numerous industry sources.

AGA Resource:

HCV Clinical Service Line: http://www.gastro.org/practice/clinical-service-line/hcv-clinical-service-line

An oral, interferon-free drug regimen produced a 97% rate of sustained virologic response in liver transplant recipients who had recurrent hepatitis C viral infection – “an historically difficult-to-treat population” at high risk of death who have extremely limited treatment options, according to a study reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an industry-sponsored, open-label phase II trial involving 34 adults with recurrent HCV infection following liver transplantation, 24 weeks of daily ombitasvir plus the ritonavir-boosted protease inhibitor ABT-450 (ABT-50/r), added to dasabuvir and ribavirin, eradicated every patient’s HCV RNA levels within 4 months. Only one patient had a relapse during a further 24 weeks of follow-up, said Dr. Parvez Mantry of the Liver Institute at Methodist Dallas, who presented the data at the meeting.*

Results of the study, which was conducted at 10 transplant centers in the United States and Spain, were presented at the meeting and simultaneously published online Nov. 11 in the New England Journal of Medicine (N. Engl. J. Med. 2014 Nov. 11 [doi: 10.1056/NEJMoa1408921]).

The standard of care for treating recurrent HCV infection after liver transplantation has been 48 weeks of peginterferon with ribavirin, but response rates are relatively low (13%-43%) because of interferon’s toxic effects. Moreover, the agent is known to induce graft injury, reducing both graft and patient survival.

The investigators assessed the safety and efficacy of a tablet formulation combining ombitasvir, a potent NS5A inhibitor, with ABT-50/r, a protease inhibitor that increases peak, trough, and overall drug exposure and allows once-daily dosing. To this was added standard dasabuvir and ribavirin, with ribavirin dosing adjusted according to the treating physician’s discretion to avert adverse hematologic effects in these immunosuppressed transplant recipients. Modified doses of standard calcineurin inhibitors (cyclosporine or tacrolimus) also were recommended for all patients, and low-dose glucocorticoids were permitted as needed.

The study participants were 18-70 years of age (mean age, 59.6 years) and had received liver transplants because of chronic HCV infection a minimum of 1 year previously. They had no or only mild liver fibrosis, were receiving stable cyclosporine- or tacrolimus-based immunosuppression, and were not coinfected with HIV or hepatitis B.

The primary efficacy endpoint was a sustained virologic response (SVR) 12 weeks after treatment was completed. All the study participants achieved an SVR by week 4 of treatment, which persisted in all of them until treatment was completed. At that time, 1 patient relapsed, so the overall SVR rate was 97%. This same SVR rate was sustained through final follow-up at post-treatment week 24.

In the patient who relapsed, HCV DNA showed resistance-associated genetic variants that had not been present at baseline. This patient also had been unresponsive to previous peginterferon-ribavirin therapy.

Adverse events were common, although the majority were mild or moderate in severity. Fatigue, headache, and cough were the most frequent adverse events. Grade 2 elevations in total bilirubin developed in two patients (6%), with no jaundice or scleral icterus. Nine patients showed grade 2 decreases in hemoglobin; none required a blood transfusion, and five required erythropoietin. There were no deaths and no cases of graft rejection.

One patient discontinued the study drug at week 18 after developing moderate rash, memory impairment, and anxiety deemed to be possibly drug related. However, that patient had already achieved an SVR before discontinuing treatment, and that SVR persisted at final follow-up 12 weeks later.

However, this study was not large enough to allow adequate assessment of adverse event rates or comparison of them with rates for other treatments, the investigators noted.

The researchers also noted that these study participants were easier to treat than the general population of liver transplant recipients with recurrent HCV, because they did not have advanced fibrosis or comorbid infections. In addition, patients with early, aggressive forms of recurrent HCV, such as fibrosing cholestatic hepatitis, were excluded from this study, as were patients maintained on immunosuppressive agents other than cyclosporine or tacrolimus.

This trial was sponsored by AbbVie, whose employees also designed the study, gathered and analyzed the data, and wrote the report. Study investigator Dr. Paul Y. Kwo reported receiving personal fees and grants from, and serving on advisory boards for, AbbVie, Bristol-Myers Squibb, and other companies. His associates reported ties to numerous industry sources.

AGA Resource:

HCV Clinical Service Line: http://www.gastro.org/practice/clinical-service-line/hcv-clinical-service-line

Infusions of rituximab proved superior to the standard of care, daily oral azathioprine, at maintaining remission of ANCA-associated vasculitis in a randomized trial.

At final follow-up after 28 months, the rate of major relapse was 5% for rituximab, compared with 29% for standard azathioprine maintenance. Rates of severe adverse events were similar in the two study groups, Dr. Loic Guillevin of Hôpital Cochin, Paris, and his associates reported in the New England Journal of Medicine.

Despite the decrease in major relapse rate with rituximab and no increase in the rate of severe adverse events, Dr. David Jayne wrote in an editorial accompanying the report that these still remain worrisome, and patients will still require prolonged observation after rituximab withdrawal. The duration of follow-up after the last rituximab dose was short in this study at only 10 months, and previous research indicates that at least half of patients will relapse after a 2-year maintenance course of the drug. Thus, the long-term risk of relapse also requires prolonged patient observation, said Dr. Jayne of the University of Cambridge (England) (N. Engl. J. Med. 2014;371:1839-40).

Dr. Guillevin and his colleagues performed the trial because maintenance of remission is still “a major challenge” in these patients, and serial rituximab infusions have not been thoroughly assessed in prospective studies. They chose to study a relatively low 500-mg dose of the drug. That dose is “lower than that used for induction or maintenance in other conditions, such as rheumatoid arthritis. We opted for this dose because enrolled patients were in remission – that is, already B-cell depleted – and with the aim of limiting the risk of infection,” they wrote.

The study participants were 115 adults who had granulomatosis with polyangiitis (87 patients), microscopic polyangiitis (23 patients), or renal-limited antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (5 patients) and were in complete remission after combined therapy using glucocorticoids plus pulsed cyclophosphamide. They were randomly assigned to receive either the experimental therapy of rituximab infusions at days 0 and 14 and at 6-month intervals for 18 months (57 patients) or the control therapy of azathioprine at 2 mg/kg per day for 12 months, then 1.5 mg/kg per day for 6 months, and finally 1 mg/kg per day for 4 months (58 patients). All patients also further tapered their prednisone dose, which was then kept low at about 5 mg/day for 18 months.

These participants were followed until month 28, which was 10 months after completing rituximab infusions or 6 months after completing oral azathioprine. The primary endpoint of the study – the percentage of patients who experienced a major relapse until the end of follow-up – was 5% for rituximab, which was significantly better than the 29% in the control group (hazard ratio, 6.61; 95% confidence interval, 1.56-27.96; P = .002). The number needed to treat with rituximab rather than azathioprine to avoid a major relapse was only 4, Dr. Guillevin and his associates reported (N. Engl. J. Med. 2014;371:1771-80).

Six patients (11%) who received rituximab and nine (16%) who received azathioprine had minor relapses.

There were no significant differences between the two groups in decreases in total immunoglobulin, IgG, or IgM levels. A total of 25 patients in each group developed at least one severe adverse event. Severe adverse infections developed in 11 patients who received rituximab (19%) and in 8 in the control group (14%). Cancers developed in one patient on rituximab and in two in the control group. There were two patient deaths, both in the control group: one from sepsis and one from pancreatic cancer.

This trial was supported by the French Ministry of Health. Hoffmann-La Roche provided rituximab for the study. Dr. Guillevin reported serving on an advisory board for GlaxoSmithKline and receiving lecture fees from Roche, Actelion, and other companies. His associates reported ties to numerous industry sources. Dr. Jayne reported ties to Sanofi/Genzyme, Roche/Genentech, and other companies.

Infusions of rituximab proved superior to the standard of care, daily oral azathioprine, at maintaining remission of ANCA-associated vasculitis in a randomized trial.

At final follow-up after 28 months, the rate of major relapse was 5% for rituximab, compared with 29% for standard azathioprine maintenance. Rates of severe adverse events were similar in the two study groups, Dr. Loic Guillevin of Hôpital Cochin, Paris, and his associates reported in the New England Journal of Medicine.

Despite the decrease in major relapse rate with rituximab and no increase in the rate of severe adverse events, Dr. David Jayne wrote in an editorial accompanying the report that these still remain worrisome, and patients will still require prolonged observation after rituximab withdrawal. The duration of follow-up after the last rituximab dose was short in this study at only 10 months, and previous research indicates that at least half of patients will relapse after a 2-year maintenance course of the drug. Thus, the long-term risk of relapse also requires prolonged patient observation, said Dr. Jayne of the University of Cambridge (England) (N. Engl. J. Med. 2014;371:1839-40).

Dr. Guillevin and his colleagues performed the trial because maintenance of remission is still “a major challenge” in these patients, and serial rituximab infusions have not been thoroughly assessed in prospective studies. They chose to study a relatively low 500-mg dose of the drug. That dose is “lower than that used for induction or maintenance in other conditions, such as rheumatoid arthritis. We opted for this dose because enrolled patients were in remission – that is, already B-cell depleted – and with the aim of limiting the risk of infection,” they wrote.

The study participants were 115 adults who had granulomatosis with polyangiitis (87 patients), microscopic polyangiitis (23 patients), or renal-limited antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (5 patients) and were in complete remission after combined therapy using glucocorticoids plus pulsed cyclophosphamide. They were randomly assigned to receive either the experimental therapy of rituximab infusions at days 0 and 14 and at 6-month intervals for 18 months (57 patients) or the control therapy of azathioprine at 2 mg/kg per day for 12 months, then 1.5 mg/kg per day for 6 months, and finally 1 mg/kg per day for 4 months (58 patients). All patients also further tapered their prednisone dose, which was then kept low at about 5 mg/day for 18 months.

These participants were followed until month 28, which was 10 months after completing rituximab infusions or 6 months after completing oral azathioprine. The primary endpoint of the study – the percentage of patients who experienced a major relapse until the end of follow-up – was 5% for rituximab, which was significantly better than the 29% in the control group (hazard ratio, 6.61; 95% confidence interval, 1.56-27.96; P = .002). The number needed to treat with rituximab rather than azathioprine to avoid a major relapse was only 4, Dr. Guillevin and his associates reported (N. Engl. J. Med. 2014;371:1771-80).

Six patients (11%) who received rituximab and nine (16%) who received azathioprine had minor relapses.

There were no significant differences between the two groups in decreases in total immunoglobulin, IgG, or IgM levels. A total of 25 patients in each group developed at least one severe adverse event. Severe adverse infections developed in 11 patients who received rituximab (19%) and in 8 in the control group (14%). Cancers developed in one patient on rituximab and in two in the control group. There were two patient deaths, both in the control group: one from sepsis and one from pancreatic cancer.

This trial was supported by the French Ministry of Health. Hoffmann-La Roche provided rituximab for the study. Dr. Guillevin reported serving on an advisory board for GlaxoSmithKline and receiving lecture fees from Roche, Actelion, and other companies. His associates reported ties to numerous industry sources. Dr. Jayne reported ties to Sanofi/Genzyme, Roche/Genentech, and other companies.

Infusions of rituximab proved superior to the standard of care, daily oral azathioprine, at maintaining remission of ANCA-associated vasculitis in a randomized trial.

At final follow-up after 28 months, the rate of major relapse was 5% for rituximab, compared with 29% for standard azathioprine maintenance. Rates of severe adverse events were similar in the two study groups, Dr. Loic Guillevin of Hôpital Cochin, Paris, and his associates reported in the New England Journal of Medicine.

Despite the decrease in major relapse rate with rituximab and no increase in the rate of severe adverse events, Dr. David Jayne wrote in an editorial accompanying the report that these still remain worrisome, and patients will still require prolonged observation after rituximab withdrawal. The duration of follow-up after the last rituximab dose was short in this study at only 10 months, and previous research indicates that at least half of patients will relapse after a 2-year maintenance course of the drug. Thus, the long-term risk of relapse also requires prolonged patient observation, said Dr. Jayne of the University of Cambridge (England) (N. Engl. J. Med. 2014;371:1839-40).

Dr. Guillevin and his colleagues performed the trial because maintenance of remission is still “a major challenge” in these patients, and serial rituximab infusions have not been thoroughly assessed in prospective studies. They chose to study a relatively low 500-mg dose of the drug. That dose is “lower than that used for induction or maintenance in other conditions, such as rheumatoid arthritis. We opted for this dose because enrolled patients were in remission – that is, already B-cell depleted – and with the aim of limiting the risk of infection,” they wrote.

The study participants were 115 adults who had granulomatosis with polyangiitis (87 patients), microscopic polyangiitis (23 patients), or renal-limited antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (5 patients) and were in complete remission after combined therapy using glucocorticoids plus pulsed cyclophosphamide. They were randomly assigned to receive either the experimental therapy of rituximab infusions at days 0 and 14 and at 6-month intervals for 18 months (57 patients) or the control therapy of azathioprine at 2 mg/kg per day for 12 months, then 1.5 mg/kg per day for 6 months, and finally 1 mg/kg per day for 4 months (58 patients). All patients also further tapered their prednisone dose, which was then kept low at about 5 mg/day for 18 months.

These participants were followed until month 28, which was 10 months after completing rituximab infusions or 6 months after completing oral azathioprine. The primary endpoint of the study – the percentage of patients who experienced a major relapse until the end of follow-up – was 5% for rituximab, which was significantly better than the 29% in the control group (hazard ratio, 6.61; 95% confidence interval, 1.56-27.96; P = .002). The number needed to treat with rituximab rather than azathioprine to avoid a major relapse was only 4, Dr. Guillevin and his associates reported (N. Engl. J. Med. 2014;371:1771-80).

Six patients (11%) who received rituximab and nine (16%) who received azathioprine had minor relapses.

There were no significant differences between the two groups in decreases in total immunoglobulin, IgG, or IgM levels. A total of 25 patients in each group developed at least one severe adverse event. Severe adverse infections developed in 11 patients who received rituximab (19%) and in 8 in the control group (14%). Cancers developed in one patient on rituximab and in two in the control group. There were two patient deaths, both in the control group: one from sepsis and one from pancreatic cancer.

This trial was supported by the French Ministry of Health. Hoffmann-La Roche provided rituximab for the study. Dr. Guillevin reported serving on an advisory board for GlaxoSmithKline and receiving lecture fees from Roche, Actelion, and other companies. His associates reported ties to numerous industry sources. Dr. Jayne reported ties to Sanofi/Genzyme, Roche/Genentech, and other companies.

For patients with early rheumatoid arthritis who achieved remission on full-dose etanercept plus methotrexate, continuing this combination treatment at a reduced dose controlled the disease better than did methotrexate alone or placebo in the randomized, controlled PRIZE trial.

The results of the PRIZE (Productivity and Remission in a Randomized Controlled Trial of Etanercept vs. Standard of Care in Early Rheumatoid Arthritis) trial, which was designed and funded by Pfizer, also showed that maintenance therapy with etanercept plus methotrexate increased the number of patients with sustained remission and extended the duration of remission after treatment was discontinued. However, it did not alter the radiographic progression of RA, said Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at Leeds (England) University, and his associates.

The trial, conducted at 57 medical centers in Europe and Asia during 2009-2012, included 193 patients who responded to the combination therapy during a 1-year, open-label phase (N. Engl. J. Med. 2014;371:1781-92).

This open-label phase consisted of subcutaneous injections of 50 mg etanercept plus oral methotrexate initiated at a dose of 10 mg/week and adjusted up to a maximum dose of 25 mg/week during the first 8 weeks. Patients who did not have low disease activity, defined as a 28-joint Disease Activity Score (DAS28) of 3.2 or less, at week 13 or 26 received glucocorticoids as rescue medication unless contraindicated or if they had unacceptable side effects.

The patients who met the criteria for response during the open-label phase by having a DAS28 of 3.2 or less at week 39 and a DAS28 of less than 2.6 at 1 year were randomly assigned in a double-blind fashion to 39 weeks of 25 mg etanercept plus methotrexate (63 participants), placebo injection plus methotrexate (65 participants), or a double placebo (65 participants). Afterward, the study treatments were withdrawn and 131 participants were followed to week 65.

The primary efficacy endpoint of the trial was the proportion of patients who had sustained remission at the end of the double-blind maintenance phase. With DAS28-defined remission, this percentage was significantly higher for patients who received etanercept plus methotrexate (79%) than for those who received methotrexate alone (54%) or placebo alone (38%). When remission was defined by the stricter American College of Rheumatology and European League Against Rheumatism (ACR-EULAR) criteria, the differences were still significant: 68%, 46%, and 23%, respectively.

At this time, 78% of patients who received combination therapy achieved a normal score on the Health Assessment Questionnaire-Disability Index (HAQ-DI), compared with 72% of those who received methotrexate alone and 45% of those who received placebo. The difference was statistically significant between the combination-therapy group and the placebo group, the investigators said.

At week 65, which was 26 weeks after all study treatments had been withdrawn, a significantly higher percentage of patients in the combination-therapy group than in the methotrexate group or the placebo group met both sets of remission criteria and still had a normal HAQ-DI score, although the percentages between the two active treatment groups were not significantly different when examining only those who met DAS28 remission criteria or those who had a normal HAQ-DI score.

But patients in the combination-therapy group remained in remission significantly longer than did those in the other study groups, and their mean DAS28 scores were significantly lower.

However, there were no differences among the three study groups in radiographic progression of RA measured at the hands, wrists, and feet at the end of the double-blind phase.

Rates of serious adverse events were 5% with combination therapy, 3% with methotrexate alone, and 3% with placebo during the maintenance phase of the trial and 0%, 0%, and 6%, respectively, during the treatment-withdrawal phase.

This study was limited in that it included only patients newly diagnosed as having RA who had not received any other treatments. Therefore the findings may not be generalizable to patients with RA of longer duration and those who have undergone other treatments, Dr. Emery and his associates said.

This study was funded by Pfizer, maker of etanercept (Enbrel); Pfizer also designed the study, collected and analyzed the data, and participated in writing the report. Dr. Emery reported ties to AbbVie, Bristol-Myers Squibb, Pfizer, UCB, Merck Sharpe & Dohme, Roche, and Takeda, and his associates reported ties to numerous industry sources.

For patients with early rheumatoid arthritis who achieved remission on full-dose etanercept plus methotrexate, continuing this combination treatment at a reduced dose controlled the disease better than did methotrexate alone or placebo in the randomized, controlled PRIZE trial.

The results of the PRIZE (Productivity and Remission in a Randomized Controlled Trial of Etanercept vs. Standard of Care in Early Rheumatoid Arthritis) trial, which was designed and funded by Pfizer, also showed that maintenance therapy with etanercept plus methotrexate increased the number of patients with sustained remission and extended the duration of remission after treatment was discontinued. However, it did not alter the radiographic progression of RA, said Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at Leeds (England) University, and his associates.

The trial, conducted at 57 medical centers in Europe and Asia during 2009-2012, included 193 patients who responded to the combination therapy during a 1-year, open-label phase (N. Engl. J. Med. 2014;371:1781-92).

This open-label phase consisted of subcutaneous injections of 50 mg etanercept plus oral methotrexate initiated at a dose of 10 mg/week and adjusted up to a maximum dose of 25 mg/week during the first 8 weeks. Patients who did not have low disease activity, defined as a 28-joint Disease Activity Score (DAS28) of 3.2 or less, at week 13 or 26 received glucocorticoids as rescue medication unless contraindicated or if they had unacceptable side effects.

The patients who met the criteria for response during the open-label phase by having a DAS28 of 3.2 or less at week 39 and a DAS28 of less than 2.6 at 1 year were randomly assigned in a double-blind fashion to 39 weeks of 25 mg etanercept plus methotrexate (63 participants), placebo injection plus methotrexate (65 participants), or a double placebo (65 participants). Afterward, the study treatments were withdrawn and 131 participants were followed to week 65.

The primary efficacy endpoint of the trial was the proportion of patients who had sustained remission at the end of the double-blind maintenance phase. With DAS28-defined remission, this percentage was significantly higher for patients who received etanercept plus methotrexate (79%) than for those who received methotrexate alone (54%) or placebo alone (38%). When remission was defined by the stricter American College of Rheumatology and European League Against Rheumatism (ACR-EULAR) criteria, the differences were still significant: 68%, 46%, and 23%, respectively.

At this time, 78% of patients who received combination therapy achieved a normal score on the Health Assessment Questionnaire-Disability Index (HAQ-DI), compared with 72% of those who received methotrexate alone and 45% of those who received placebo. The difference was statistically significant between the combination-therapy group and the placebo group, the investigators said.

At week 65, which was 26 weeks after all study treatments had been withdrawn, a significantly higher percentage of patients in the combination-therapy group than in the methotrexate group or the placebo group met both sets of remission criteria and still had a normal HAQ-DI score, although the percentages between the two active treatment groups were not significantly different when examining only those who met DAS28 remission criteria or those who had a normal HAQ-DI score.

But patients in the combination-therapy group remained in remission significantly longer than did those in the other study groups, and their mean DAS28 scores were significantly lower.

However, there were no differences among the three study groups in radiographic progression of RA measured at the hands, wrists, and feet at the end of the double-blind phase.

Rates of serious adverse events were 5% with combination therapy, 3% with methotrexate alone, and 3% with placebo during the maintenance phase of the trial and 0%, 0%, and 6%, respectively, during the treatment-withdrawal phase.

This study was limited in that it included only patients newly diagnosed as having RA who had not received any other treatments. Therefore the findings may not be generalizable to patients with RA of longer duration and those who have undergone other treatments, Dr. Emery and his associates said.

This study was funded by Pfizer, maker of etanercept (Enbrel); Pfizer also designed the study, collected and analyzed the data, and participated in writing the report. Dr. Emery reported ties to AbbVie, Bristol-Myers Squibb, Pfizer, UCB, Merck Sharpe & Dohme, Roche, and Takeda, and his associates reported ties to numerous industry sources.

For patients with early rheumatoid arthritis who achieved remission on full-dose etanercept plus methotrexate, continuing this combination treatment at a reduced dose controlled the disease better than did methotrexate alone or placebo in the randomized, controlled PRIZE trial.

The results of the PRIZE (Productivity and Remission in a Randomized Controlled Trial of Etanercept vs. Standard of Care in Early Rheumatoid Arthritis) trial, which was designed and funded by Pfizer, also showed that maintenance therapy with etanercept plus methotrexate increased the number of patients with sustained remission and extended the duration of remission after treatment was discontinued. However, it did not alter the radiographic progression of RA, said Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at Leeds (England) University, and his associates.

The trial, conducted at 57 medical centers in Europe and Asia during 2009-2012, included 193 patients who responded to the combination therapy during a 1-year, open-label phase (N. Engl. J. Med. 2014;371:1781-92).

This open-label phase consisted of subcutaneous injections of 50 mg etanercept plus oral methotrexate initiated at a dose of 10 mg/week and adjusted up to a maximum dose of 25 mg/week during the first 8 weeks. Patients who did not have low disease activity, defined as a 28-joint Disease Activity Score (DAS28) of 3.2 or less, at week 13 or 26 received glucocorticoids as rescue medication unless contraindicated or if they had unacceptable side effects.

The patients who met the criteria for response during the open-label phase by having a DAS28 of 3.2 or less at week 39 and a DAS28 of less than 2.6 at 1 year were randomly assigned in a double-blind fashion to 39 weeks of 25 mg etanercept plus methotrexate (63 participants), placebo injection plus methotrexate (65 participants), or a double placebo (65 participants). Afterward, the study treatments were withdrawn and 131 participants were followed to week 65.

The primary efficacy endpoint of the trial was the proportion of patients who had sustained remission at the end of the double-blind maintenance phase. With DAS28-defined remission, this percentage was significantly higher for patients who received etanercept plus methotrexate (79%) than for those who received methotrexate alone (54%) or placebo alone (38%). When remission was defined by the stricter American College of Rheumatology and European League Against Rheumatism (ACR-EULAR) criteria, the differences were still significant: 68%, 46%, and 23%, respectively.

At this time, 78% of patients who received combination therapy achieved a normal score on the Health Assessment Questionnaire-Disability Index (HAQ-DI), compared with 72% of those who received methotrexate alone and 45% of those who received placebo. The difference was statistically significant between the combination-therapy group and the placebo group, the investigators said.

At week 65, which was 26 weeks after all study treatments had been withdrawn, a significantly higher percentage of patients in the combination-therapy group than in the methotrexate group or the placebo group met both sets of remission criteria and still had a normal HAQ-DI score, although the percentages between the two active treatment groups were not significantly different when examining only those who met DAS28 remission criteria or those who had a normal HAQ-DI score.

But patients in the combination-therapy group remained in remission significantly longer than did those in the other study groups, and their mean DAS28 scores were significantly lower.

However, there were no differences among the three study groups in radiographic progression of RA measured at the hands, wrists, and feet at the end of the double-blind phase.

Rates of serious adverse events were 5% with combination therapy, 3% with methotrexate alone, and 3% with placebo during the maintenance phase of the trial and 0%, 0%, and 6%, respectively, during the treatment-withdrawal phase.

This study was limited in that it included only patients newly diagnosed as having RA who had not received any other treatments. Therefore the findings may not be generalizable to patients with RA of longer duration and those who have undergone other treatments, Dr. Emery and his associates said.

This study was funded by Pfizer, maker of etanercept (Enbrel); Pfizer also designed the study, collected and analyzed the data, and participated in writing the report. Dr. Emery reported ties to AbbVie, Bristol-Myers Squibb, Pfizer, UCB, Merck Sharpe & Dohme, Roche, and Takeda, and his associates reported ties to numerous industry sources.

No studies have yet assessed the efficacy of intensive behavioral weight-loss counseling delivered in the primary care setting in accordance with Medicare/Medicaid requirements, according to a systematic review of the literature published online Nov. 4 in JAMA.

The U.S. Preventive Services Task Force recommends that all primary care physicians screen all their adult patients for obesity and offer the affected patients such intensive counseling, either by providing it themselves or by referral, said Thomas A. Wadden, Ph.D., of the Center for Weight and Eating Disorders, University of Pennsylvania, Philadelphia, and his associates.

© DAJ/Thinkstock

In 2011, the Centers for Medicare & Medicaid Services (CMS) approved the provision of intensive behavioral counseling for obese beneficiaries seen in primary care practices for approximately 14 face-to-face sessions over 6 months when delivered by physicians and other select practitioners. While the CMS covers the costs of such counseling, it does so only when counseling meets specifics on treatment intensity, who may provide it, and where it may be provided.

In their systematic review, the investigators identified 3,304 articles on the topic, and winnowed their detailed review to 12 good-quality trials involving 3,893 participants. They found that to date, not a single study has assessed even one real-world primary care practice that complies with all the CMS requirements.

Data from two of the reviewed clinical trials supported the “treatment intensity” requirement, which is that intensive behavioral weight-loss counseling must include approximately 14 face-to-face sessions during the initial 6 months: weekly sessions for the first month, every-other-week sessions for months 2-6, and monthly sessions during months 7-12. In these two studies, participants attended three sessions with the primary care physician and eight with a trained interventionist for 6 months, and achieved mean weight losses of 4.4 kg and 3.5 kg, respectively.

However, one of these trials substituted brief telephone sessions with trained interventionists at a call center for face-to-face interviews, with good results. “A growing literature suggests that telephone-delivered counseling is generally as effective as traditional face-to-face contact, potentially is more convenient and less costly for patients, and can reach more individuals in underserved areas,” Dr. Wadden and his associates said (JAMA 2014 Nov. 4 [doi: 10.1001/jama.2014.14173]).

Similarly, data from three trials supported the requirement that counseling be provided by trained medical assistants in collaboration with primary care physicians. Weight loss achieved with this approach was far greater than that achieved with counseling provided by trained interventionists who had limited or no collaboration with the primary care physicians. The results of several trials confirmed the requirement that this counseling must be comprehensive, incorporating a dietary component, an exercise component, and a behavioral component to maximize results. In particular, interventions that provided specific goals for energy restriction and expenditure were successful, whereas those that did not were unsuccessful, the investigators said.

This study was funded in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadden and his associates reported ties to Novo Nordisk, Nutrisystem, Orexigen, Shire Pharmaceuticals, and Weight Watchers.

No studies have yet assessed the efficacy of intensive behavioral weight-loss counseling delivered in the primary care setting in accordance with Medicare/Medicaid requirements, according to a systematic review of the literature published online Nov. 4 in JAMA.

The U.S. Preventive Services Task Force recommends that all primary care physicians screen all their adult patients for obesity and offer the affected patients such intensive counseling, either by providing it themselves or by referral, said Thomas A. Wadden, Ph.D., of the Center for Weight and Eating Disorders, University of Pennsylvania, Philadelphia, and his associates.

© DAJ/Thinkstock

In 2011, the Centers for Medicare & Medicaid Services (CMS) approved the provision of intensive behavioral counseling for obese beneficiaries seen in primary care practices for approximately 14 face-to-face sessions over 6 months when delivered by physicians and other select practitioners. While the CMS covers the costs of such counseling, it does so only when counseling meets specifics on treatment intensity, who may provide it, and where it may be provided.

In their systematic review, the investigators identified 3,304 articles on the topic, and winnowed their detailed review to 12 good-quality trials involving 3,893 participants. They found that to date, not a single study has assessed even one real-world primary care practice that complies with all the CMS requirements.

Data from two of the reviewed clinical trials supported the “treatment intensity” requirement, which is that intensive behavioral weight-loss counseling must include approximately 14 face-to-face sessions during the initial 6 months: weekly sessions for the first month, every-other-week sessions for months 2-6, and monthly sessions during months 7-12. In these two studies, participants attended three sessions with the primary care physician and eight with a trained interventionist for 6 months, and achieved mean weight losses of 4.4 kg and 3.5 kg, respectively.

However, one of these trials substituted brief telephone sessions with trained interventionists at a call center for face-to-face interviews, with good results. “A growing literature suggests that telephone-delivered counseling is generally as effective as traditional face-to-face contact, potentially is more convenient and less costly for patients, and can reach more individuals in underserved areas,” Dr. Wadden and his associates said (JAMA 2014 Nov. 4 [doi: 10.1001/jama.2014.14173]).

Similarly, data from three trials supported the requirement that counseling be provided by trained medical assistants in collaboration with primary care physicians. Weight loss achieved with this approach was far greater than that achieved with counseling provided by trained interventionists who had limited or no collaboration with the primary care physicians. The results of several trials confirmed the requirement that this counseling must be comprehensive, incorporating a dietary component, an exercise component, and a behavioral component to maximize results. In particular, interventions that provided specific goals for energy restriction and expenditure were successful, whereas those that did not were unsuccessful, the investigators said.

This study was funded in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadden and his associates reported ties to Novo Nordisk, Nutrisystem, Orexigen, Shire Pharmaceuticals, and Weight Watchers.

No studies have yet assessed the efficacy of intensive behavioral weight-loss counseling delivered in the primary care setting in accordance with Medicare/Medicaid requirements, according to a systematic review of the literature published online Nov. 4 in JAMA.

The U.S. Preventive Services Task Force recommends that all primary care physicians screen all their adult patients for obesity and offer the affected patients such intensive counseling, either by providing it themselves or by referral, said Thomas A. Wadden, Ph.D., of the Center for Weight and Eating Disorders, University of Pennsylvania, Philadelphia, and his associates.

© DAJ/Thinkstock

In 2011, the Centers for Medicare & Medicaid Services (CMS) approved the provision of intensive behavioral counseling for obese beneficiaries seen in primary care practices for approximately 14 face-to-face sessions over 6 months when delivered by physicians and other select practitioners. While the CMS covers the costs of such counseling, it does so only when counseling meets specifics on treatment intensity, who may provide it, and where it may be provided.

In their systematic review, the investigators identified 3,304 articles on the topic, and winnowed their detailed review to 12 good-quality trials involving 3,893 participants. They found that to date, not a single study has assessed even one real-world primary care practice that complies with all the CMS requirements.

Data from two of the reviewed clinical trials supported the “treatment intensity” requirement, which is that intensive behavioral weight-loss counseling must include approximately 14 face-to-face sessions during the initial 6 months: weekly sessions for the first month, every-other-week sessions for months 2-6, and monthly sessions during months 7-12. In these two studies, participants attended three sessions with the primary care physician and eight with a trained interventionist for 6 months, and achieved mean weight losses of 4.4 kg and 3.5 kg, respectively.

However, one of these trials substituted brief telephone sessions with trained interventionists at a call center for face-to-face interviews, with good results. “A growing literature suggests that telephone-delivered counseling is generally as effective as traditional face-to-face contact, potentially is more convenient and less costly for patients, and can reach more individuals in underserved areas,” Dr. Wadden and his associates said (JAMA 2014 Nov. 4 [doi: 10.1001/jama.2014.14173]).

Similarly, data from three trials supported the requirement that counseling be provided by trained medical assistants in collaboration with primary care physicians. Weight loss achieved with this approach was far greater than that achieved with counseling provided by trained interventionists who had limited or no collaboration with the primary care physicians. The results of several trials confirmed the requirement that this counseling must be comprehensive, incorporating a dietary component, an exercise component, and a behavioral component to maximize results. In particular, interventions that provided specific goals for energy restriction and expenditure were successful, whereas those that did not were unsuccessful, the investigators said.

This study was funded in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadden and his associates reported ties to Novo Nordisk, Nutrisystem, Orexigen, Shire Pharmaceuticals, and Weight Watchers.

The greatest research need regarding bariatric surgery is the critical lack of information about long-term durability and complications of the procedures, according to a report published online Nov. 4 in JAMA Surgery.

Bariatric surgery “results in greater weight loss than nonsurgical treatment,” but that crucial information about long-term outcomes – “at least 10 years’ worth” – is still missing, said Dr. Bruce M. Wolfe of Oregon Health and Science University, Portland, and Steven H. Belle, Ph.D., of the epidemiology department, University of Pittsburgh. They were speaking at a symposium sponsored by the National Institute of Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute to review the best available evidence on bariatric surgery outcomes from the most recent large observational studies and randomized clinical trials.

Very large multicenter, randomized, controlled trials are the best type of study to provide this information but are prohibitively expensive, especially given the difficulty retaining participants in weight-loss studies. Any such trial would require very large numbers of treatment centers and patients to generate results that were adequately powered and generalizable, they wrote (JAMA Surg. 2014 Nov. 4 [doi: 10.1001/jamasurg.2014.2440]).

Future research must address the substantial variability in weight loss after bariatric surgery, as well as the equally substantial variability in its effect on diabetes, hypertension, dyslipidemia, obstructive sleep apnea, and psychological and psychosocial issues. And long-term gastrointestinal complications must be a specific focus because these procedures alter the GI anatomy, and adverse effects may take many years to manifest.

“In summary, bariatric surgery offers the potential to address the morbidity and mortality of the obesity epidemic, but important research questions remain unresolved,” according to Dr. Wolfe and Dr. Belle.

The symposium was convened by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute’s division of cardiovascular sciences. Dr. Wolfe reported serving as a research consultant to EnteroMedics.

fpnews@frontlinemedcom.com

The greatest research need regarding bariatric surgery is the critical lack of information about long-term durability and complications of the procedures, according to a report published online Nov. 4 in JAMA Surgery.

Bariatric surgery “results in greater weight loss than nonsurgical treatment,” but that crucial information about long-term outcomes – “at least 10 years’ worth” – is still missing, said Dr. Bruce M. Wolfe of Oregon Health and Science University, Portland, and Steven H. Belle, Ph.D., of the epidemiology department, University of Pittsburgh. They were speaking at a symposium sponsored by the National Institute of Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute to review the best available evidence on bariatric surgery outcomes from the most recent large observational studies and randomized clinical trials.

Very large multicenter, randomized, controlled trials are the best type of study to provide this information but are prohibitively expensive, especially given the difficulty retaining participants in weight-loss studies. Any such trial would require very large numbers of treatment centers and patients to generate results that were adequately powered and generalizable, they wrote (JAMA Surg. 2014 Nov. 4 [doi: 10.1001/jamasurg.2014.2440]).

Future research must address the substantial variability in weight loss after bariatric surgery, as well as the equally substantial variability in its effect on diabetes, hypertension, dyslipidemia, obstructive sleep apnea, and psychological and psychosocial issues. And long-term gastrointestinal complications must be a specific focus because these procedures alter the GI anatomy, and adverse effects may take many years to manifest.

“In summary, bariatric surgery offers the potential to address the morbidity and mortality of the obesity epidemic, but important research questions remain unresolved,” according to Dr. Wolfe and Dr. Belle.

The symposium was convened by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute’s division of cardiovascular sciences. Dr. Wolfe reported serving as a research consultant to EnteroMedics.

fpnews@frontlinemedcom.com

The greatest research need regarding bariatric surgery is the critical lack of information about long-term durability and complications of the procedures, according to a report published online Nov. 4 in JAMA Surgery.

Bariatric surgery “results in greater weight loss than nonsurgical treatment,” but that crucial information about long-term outcomes – “at least 10 years’ worth” – is still missing, said Dr. Bruce M. Wolfe of Oregon Health and Science University, Portland, and Steven H. Belle, Ph.D., of the epidemiology department, University of Pittsburgh. They were speaking at a symposium sponsored by the National Institute of Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute to review the best available evidence on bariatric surgery outcomes from the most recent large observational studies and randomized clinical trials.

Very large multicenter, randomized, controlled trials are the best type of study to provide this information but are prohibitively expensive, especially given the difficulty retaining participants in weight-loss studies. Any such trial would require very large numbers of treatment centers and patients to generate results that were adequately powered and generalizable, they wrote (JAMA Surg. 2014 Nov. 4 [doi: 10.1001/jamasurg.2014.2440]).

Future research must address the substantial variability in weight loss after bariatric surgery, as well as the equally substantial variability in its effect on diabetes, hypertension, dyslipidemia, obstructive sleep apnea, and psychological and psychosocial issues. And long-term gastrointestinal complications must be a specific focus because these procedures alter the GI anatomy, and adverse effects may take many years to manifest.

“In summary, bariatric surgery offers the potential to address the morbidity and mortality of the obesity epidemic, but important research questions remain unresolved,” according to Dr. Wolfe and Dr. Belle.

The symposium was convened by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute’s division of cardiovascular sciences. Dr. Wolfe reported serving as a research consultant to EnteroMedics.

fpnews@frontlinemedcom.com