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Bezafibrate shows promise as second-line option for PBC
Nearly one-third of patients with primary biliary cholangitis treated with bezafibrate showed clinical improvement after 24 months, according to data from a randomized trial of 100 adults.
Ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), but many patients have an incomplete response to the treatment, and consequently their long-term survival is limited, wrote Christophe Corpechot, MD, of Sorbonne University, Paris, and his colleagues. PBC is also known as primary biliary cirrhosis.
In the BEZURSO trial (Bezafibrate in Combination with Ursodeoxycholic Acid in Primary Biliary Cirrhosis), published in the New England Journal of Medicine, the researchers randomized 100 primary PBC patients with an inadequate response to ursodeoxycholic acid to receive 400 mg per day of bezafibrate or a placebo for 24 months. Inadequate response was defined as “a serum level of alkaline phosphatase or aspartate aminotransferase more than 1.5 times the upper limit of the normal range or an abnormal total bilirubin level, assessed after at least 6 months of treatment with ursodeoxycholic acid,” the researchers said.
Baseline demographics were not significantly different between the groups. The average age of the patients was 53 years, and 95% were white women.
After 24 months, 31% of the patients in the treatment group met the primary outcome, which was the achievement of normal levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin, plus a normal prothrombin index. By contrast, none of the patients in the placebo group achieved the primary outcome.
In particular, bezafibrate patients showed a 60% reduction in alkaline phosphatase levels from baseline to 3 months, and a 14% decrease in total bilirubin from baseline during the course of the study.
Clinical outcomes were similar between the groups; 20% of the bezafibrate group and 18% of the placebo group developed portal hypertension, and two patients in each group developed liver complications. No deaths occurred in either group during the study. Approximately half of the patients in each group reported adverse events. Serious adverse events occurred in 14 bezafibrate patients and 12 placebo patients.
The findings were limited by the small study population, which prevented assessment of bezafibrate on liver transplantation and death, and by the limited histologic data to look at the impact on liver fibrosis and hepatic inflammation, the researchers said.
However, the results support the use of bezafibrate as an add-on to ursodeoxycholic acid in PBC patients, and merit larger, longer studies, they noted.
The study was supported by the Programme Hospitalier de Recherche Clinique 2010, Ministry of Health, and Arrow Génériques. Dr. Corpechot disclosed relationships with companies including Intercept France, Inventiva Pharma, and GlaxoSmithKline.
SOURCE: Corpechot C et al. N Engl J Med. 2018 June 6. doi: 10.1056/NEJMoa1714519.
The BEZURSO study findings “merit cautious excitement,” Elizabeth J. Carey, MD, wrote in an editorial.
“This pivotal trial effectively doubles the limited options for second-line therapy of primary biliary cholangitis,” she said.
Approximately 40% of primary biliary cholangitis patients fail to respond adequately to ursodeoxycholic acid, the first-line therapy, and they remain at risk for progression of liver disease and liver failure, wrote Dr. Carey. Bezafibrate is the first drug to generate improvement in these patients not only in measures of biochemical markers, but also measures of fibrosis and disease symptoms, she said. Patient reports of reduced itching and lower levels of fatigue are worth noting, although they were not the primary outcomes, said Dr. Carey.
“Improvement in patient-reported outcomes prompts the question of whether there is a role for the use of bezafibrate for the management of fatigue or pruritus, even in patients who have a biochemical response to ursodeoxycholic acid,” she noted (N Engl J Med. 2018 June 6. doi: 10.1056/NEJMe1804945).
Despite the promising results, challenges remain for primary biliary cholangitis patients, as approximately 70% did not meet the primary outcome, and those with more severe disease were less likely to respond, Dr. Carey said. However, she added, any agent “that both delays disease progression and alleviates symptoms is a potential boon for patients with the debilitating symptoms of primary biliary cholangitis.”
Dr. Carey is affiliated with the Mayo Clinic in Phoenix, Ariz. Disclosure forms provided by the author are available at NEJM.org.
The BEZURSO study findings “merit cautious excitement,” Elizabeth J. Carey, MD, wrote in an editorial.
“This pivotal trial effectively doubles the limited options for second-line therapy of primary biliary cholangitis,” she said.
Approximately 40% of primary biliary cholangitis patients fail to respond adequately to ursodeoxycholic acid, the first-line therapy, and they remain at risk for progression of liver disease and liver failure, wrote Dr. Carey. Bezafibrate is the first drug to generate improvement in these patients not only in measures of biochemical markers, but also measures of fibrosis and disease symptoms, she said. Patient reports of reduced itching and lower levels of fatigue are worth noting, although they were not the primary outcomes, said Dr. Carey.
“Improvement in patient-reported outcomes prompts the question of whether there is a role for the use of bezafibrate for the management of fatigue or pruritus, even in patients who have a biochemical response to ursodeoxycholic acid,” she noted (N Engl J Med. 2018 June 6. doi: 10.1056/NEJMe1804945).
Despite the promising results, challenges remain for primary biliary cholangitis patients, as approximately 70% did not meet the primary outcome, and those with more severe disease were less likely to respond, Dr. Carey said. However, she added, any agent “that both delays disease progression and alleviates symptoms is a potential boon for patients with the debilitating symptoms of primary biliary cholangitis.”
Dr. Carey is affiliated with the Mayo Clinic in Phoenix, Ariz. Disclosure forms provided by the author are available at NEJM.org.
The BEZURSO study findings “merit cautious excitement,” Elizabeth J. Carey, MD, wrote in an editorial.
“This pivotal trial effectively doubles the limited options for second-line therapy of primary biliary cholangitis,” she said.
Approximately 40% of primary biliary cholangitis patients fail to respond adequately to ursodeoxycholic acid, the first-line therapy, and they remain at risk for progression of liver disease and liver failure, wrote Dr. Carey. Bezafibrate is the first drug to generate improvement in these patients not only in measures of biochemical markers, but also measures of fibrosis and disease symptoms, she said. Patient reports of reduced itching and lower levels of fatigue are worth noting, although they were not the primary outcomes, said Dr. Carey.
“Improvement in patient-reported outcomes prompts the question of whether there is a role for the use of bezafibrate for the management of fatigue or pruritus, even in patients who have a biochemical response to ursodeoxycholic acid,” she noted (N Engl J Med. 2018 June 6. doi: 10.1056/NEJMe1804945).
Despite the promising results, challenges remain for primary biliary cholangitis patients, as approximately 70% did not meet the primary outcome, and those with more severe disease were less likely to respond, Dr. Carey said. However, she added, any agent “that both delays disease progression and alleviates symptoms is a potential boon for patients with the debilitating symptoms of primary biliary cholangitis.”
Dr. Carey is affiliated with the Mayo Clinic in Phoenix, Ariz. Disclosure forms provided by the author are available at NEJM.org.
Nearly one-third of patients with primary biliary cholangitis treated with bezafibrate showed clinical improvement after 24 months, according to data from a randomized trial of 100 adults.
Ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), but many patients have an incomplete response to the treatment, and consequently their long-term survival is limited, wrote Christophe Corpechot, MD, of Sorbonne University, Paris, and his colleagues. PBC is also known as primary biliary cirrhosis.
In the BEZURSO trial (Bezafibrate in Combination with Ursodeoxycholic Acid in Primary Biliary Cirrhosis), published in the New England Journal of Medicine, the researchers randomized 100 primary PBC patients with an inadequate response to ursodeoxycholic acid to receive 400 mg per day of bezafibrate or a placebo for 24 months. Inadequate response was defined as “a serum level of alkaline phosphatase or aspartate aminotransferase more than 1.5 times the upper limit of the normal range or an abnormal total bilirubin level, assessed after at least 6 months of treatment with ursodeoxycholic acid,” the researchers said.
Baseline demographics were not significantly different between the groups. The average age of the patients was 53 years, and 95% were white women.
After 24 months, 31% of the patients in the treatment group met the primary outcome, which was the achievement of normal levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin, plus a normal prothrombin index. By contrast, none of the patients in the placebo group achieved the primary outcome.
In particular, bezafibrate patients showed a 60% reduction in alkaline phosphatase levels from baseline to 3 months, and a 14% decrease in total bilirubin from baseline during the course of the study.
Clinical outcomes were similar between the groups; 20% of the bezafibrate group and 18% of the placebo group developed portal hypertension, and two patients in each group developed liver complications. No deaths occurred in either group during the study. Approximately half of the patients in each group reported adverse events. Serious adverse events occurred in 14 bezafibrate patients and 12 placebo patients.
The findings were limited by the small study population, which prevented assessment of bezafibrate on liver transplantation and death, and by the limited histologic data to look at the impact on liver fibrosis and hepatic inflammation, the researchers said.
However, the results support the use of bezafibrate as an add-on to ursodeoxycholic acid in PBC patients, and merit larger, longer studies, they noted.
The study was supported by the Programme Hospitalier de Recherche Clinique 2010, Ministry of Health, and Arrow Génériques. Dr. Corpechot disclosed relationships with companies including Intercept France, Inventiva Pharma, and GlaxoSmithKline.
SOURCE: Corpechot C et al. N Engl J Med. 2018 June 6. doi: 10.1056/NEJMoa1714519.
Nearly one-third of patients with primary biliary cholangitis treated with bezafibrate showed clinical improvement after 24 months, according to data from a randomized trial of 100 adults.
Ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), but many patients have an incomplete response to the treatment, and consequently their long-term survival is limited, wrote Christophe Corpechot, MD, of Sorbonne University, Paris, and his colleagues. PBC is also known as primary biliary cirrhosis.
In the BEZURSO trial (Bezafibrate in Combination with Ursodeoxycholic Acid in Primary Biliary Cirrhosis), published in the New England Journal of Medicine, the researchers randomized 100 primary PBC patients with an inadequate response to ursodeoxycholic acid to receive 400 mg per day of bezafibrate or a placebo for 24 months. Inadequate response was defined as “a serum level of alkaline phosphatase or aspartate aminotransferase more than 1.5 times the upper limit of the normal range or an abnormal total bilirubin level, assessed after at least 6 months of treatment with ursodeoxycholic acid,” the researchers said.
Baseline demographics were not significantly different between the groups. The average age of the patients was 53 years, and 95% were white women.
After 24 months, 31% of the patients in the treatment group met the primary outcome, which was the achievement of normal levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin, plus a normal prothrombin index. By contrast, none of the patients in the placebo group achieved the primary outcome.
In particular, bezafibrate patients showed a 60% reduction in alkaline phosphatase levels from baseline to 3 months, and a 14% decrease in total bilirubin from baseline during the course of the study.
Clinical outcomes were similar between the groups; 20% of the bezafibrate group and 18% of the placebo group developed portal hypertension, and two patients in each group developed liver complications. No deaths occurred in either group during the study. Approximately half of the patients in each group reported adverse events. Serious adverse events occurred in 14 bezafibrate patients and 12 placebo patients.
The findings were limited by the small study population, which prevented assessment of bezafibrate on liver transplantation and death, and by the limited histologic data to look at the impact on liver fibrosis and hepatic inflammation, the researchers said.
However, the results support the use of bezafibrate as an add-on to ursodeoxycholic acid in PBC patients, and merit larger, longer studies, they noted.
The study was supported by the Programme Hospitalier de Recherche Clinique 2010, Ministry of Health, and Arrow Génériques. Dr. Corpechot disclosed relationships with companies including Intercept France, Inventiva Pharma, and GlaxoSmithKline.
SOURCE: Corpechot C et al. N Engl J Med. 2018 June 6. doi: 10.1056/NEJMoa1714519.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Primary biliary cholangitis patients who took bezafibrate showed decreases in alkaline phosphatase levels and total bilirubin.
Major finding: A total of 31% of patients who took bezafibrate achieved normal levels of disease biomarkers after 24 months compared with 0% of placebo patients.
Study details: The data come from a double-blind, placebo-controlled trial of 100 adults with primary biliary cholangitis at 21 medical centers in France.
Disclosures: Programme Hospitalier de Recherche Clinique 2010 (Ministry of Health) and Arrow Génériques supported the study. Dr. Corpechot disclosed relationships with companies including Intercept France, Inventiva Pharma, and GlaxoSmithKline.
Source: Corpechot C et al. N Engl J Med. 2018 June 6. doi: 10.1056/NEJMoa1714519.
FDA alerts clinicians to gastric balloon deaths
according to an alert from the Food and Drug Administration issued on June 4.
Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.
The FDA has approved updated labeling for the ORBERA and ReShape balloon systems in the United States. The labels contain more information about possible death associated with the use of these devices in the United States. The manufacturers’ sites, Apollo Endosurgery and ReShape Lifesciences, provide more details about the new labeling.
In a letter to health care providers, the FDA advised clinicians to educate bariatric surgery patients about the symptoms of complications from balloon procedures, including not only gastric perforation but also esophageal perforation, balloon deflation, gastrointestinal obstruction, and ulceration. In addition, the FDA reminded clinicians to monitor patients during the entire course of treatment for additional complications, including acute pancreatitis and spontaneous hyperinflation.
Any adverse events involving intragastric balloon systems should be reported to the FDA through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
according to an alert from the Food and Drug Administration issued on June 4.
Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.
The FDA has approved updated labeling for the ORBERA and ReShape balloon systems in the United States. The labels contain more information about possible death associated with the use of these devices in the United States. The manufacturers’ sites, Apollo Endosurgery and ReShape Lifesciences, provide more details about the new labeling.
In a letter to health care providers, the FDA advised clinicians to educate bariatric surgery patients about the symptoms of complications from balloon procedures, including not only gastric perforation but also esophageal perforation, balloon deflation, gastrointestinal obstruction, and ulceration. In addition, the FDA reminded clinicians to monitor patients during the entire course of treatment for additional complications, including acute pancreatitis and spontaneous hyperinflation.
Any adverse events involving intragastric balloon systems should be reported to the FDA through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
according to an alert from the Food and Drug Administration issued on June 4.
Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.
The FDA has approved updated labeling for the ORBERA and ReShape balloon systems in the United States. The labels contain more information about possible death associated with the use of these devices in the United States. The manufacturers’ sites, Apollo Endosurgery and ReShape Lifesciences, provide more details about the new labeling.
In a letter to health care providers, the FDA advised clinicians to educate bariatric surgery patients about the symptoms of complications from balloon procedures, including not only gastric perforation but also esophageal perforation, balloon deflation, gastrointestinal obstruction, and ulceration. In addition, the FDA reminded clinicians to monitor patients during the entire course of treatment for additional complications, including acute pancreatitis and spontaneous hyperinflation.
Any adverse events involving intragastric balloon systems should be reported to the FDA through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
Hospital safety program curbs surgical site infections
The Agency for Healthcare Research and Quality (AHRQ) designed the program to reduce surgical site infections (SSIs), which are harmful to patients and expensive for the health care system, wrote Della M. Lin, MD, of Johns Hopkins University, Baltimore, and the department of surgery at the University of Hawaii, Honolulu, and her colleagues.
In a study published in the Journal of the American College of Surgeons, the researchers reviewed data from a statewide intervention conducted at 15 hospitals in Hawaii from January 2013 to June 2015. The intervention included the Comprehensive Unit-based Safety Program and individualized interventions for each hospital to help reduce SSIs. The primary outcome was the number of colorectal SSIs. A secondary outcome of hospital safety culture was assessed using the AHRQ Hospital Survey on Patient Safety Culture. The participating hospitals ranged from a 25-bed critical-access hospital to a 533-bed academic medical center.
Overall, the colorectal SSI rate decreased significantly (from 12% to 5%) from the first quarter of 2013 to the second quarter of 2015, with a significant linear decrease over the study period. The rate of superficial SSIs decreased significantly, falling from 8% to 3%. However, the rate of deep SSIs was not significantly different before and after the intervention program (2% vs. 0%), nor was the organ space SSI rate (3% vs. 2%). The standardized infection ratio decreased from 1.83 to 0.92.
The culture of safety in the hospitals improved, but more modestly, in 10 of 12 areas that were measured over the study period.
The overall perception of patient safety improved from 49% to 53%, teamwork across different units improved from 49% to 54%, management and support for patient safety improved from 53% to 60%, and nonpunitive response to errors improved from 36% to 40%.
In addition, communication and openness improved from 50% to 53%, frequency of reported events improved from 51% to 60%, feedback and communication about errors improved from 52% to 59%, organizational learning and continuous improvement increased from 59% to 70%, teamwork within units improved from 68% to 75%, and expectations and actions by supervisors and managers to promote safety improved from 58% to 64%. Staff responses reflect agreement on improvement in the areas of issues of communication, feedback mechanisms, and teamwork, but the change in culture was not on the order of the SSI change.
The most common interventions to reduce SSIs were the use of reliable chlorhexidine wash or wipe before surgery/surgical prep; appropriate use of antibiotics with respect to selection, dosage, and timing; standardized postsurgical debriefing; and differentiating clean/dirty/clean in the use of anastomosis trays and closing trays.
One bundle component, the implementation of the standard operating room debrief, was found to be of particular value to participants. The investigators noted that debrief questions such as “What went well?” and “What needs to be improved?” had “encouraged new processes of thinking beyond first-order problem solving. The debrief challenge embraced by the teams emphasized that ‘bundles’ did not consist of only technical interventions [e.g. clean/dirty trays, chlorhexidine gluconate wipes in preop], but embedded culture interventions—new processes for problem solving.”
The study findings were limited by several factors, such as the use of public SSI data that were not audited for accuracy and the inability to monitor the reliability of the implementation of the various interventions, the researchers said. In addition, “In this current study, there was a change in SSI rates and a change in safety culture, but correlations between the two were negligible or weak for most domains of safety culture,” they noted. The question of sustainability of the SSI improvement without the concomitant staff support of culture change was not addressed by the investigators.
However, the results suggest that a 62% decrease is robust, and that for some hospitals with a low volume of colorectal cases, “teams could attend to iteratively reduce surgical harm beyond SSI,” the researchers wrote.
The study was supported in part by the AHRQ. Dr. Lin disclosed serving as a board member and as a paid independent contractor to the Hawaii Medical Service Association. Her coauthors had no financial conflicts to disclose.
SOURCE: Lin DM et al. J Am Coll Surg. 2018 May 18. doi: 10.1016/j.jamcollsurg.2018.04.031.
The Agency for Healthcare Research and Quality (AHRQ) designed the program to reduce surgical site infections (SSIs), which are harmful to patients and expensive for the health care system, wrote Della M. Lin, MD, of Johns Hopkins University, Baltimore, and the department of surgery at the University of Hawaii, Honolulu, and her colleagues.
In a study published in the Journal of the American College of Surgeons, the researchers reviewed data from a statewide intervention conducted at 15 hospitals in Hawaii from January 2013 to June 2015. The intervention included the Comprehensive Unit-based Safety Program and individualized interventions for each hospital to help reduce SSIs. The primary outcome was the number of colorectal SSIs. A secondary outcome of hospital safety culture was assessed using the AHRQ Hospital Survey on Patient Safety Culture. The participating hospitals ranged from a 25-bed critical-access hospital to a 533-bed academic medical center.
Overall, the colorectal SSI rate decreased significantly (from 12% to 5%) from the first quarter of 2013 to the second quarter of 2015, with a significant linear decrease over the study period. The rate of superficial SSIs decreased significantly, falling from 8% to 3%. However, the rate of deep SSIs was not significantly different before and after the intervention program (2% vs. 0%), nor was the organ space SSI rate (3% vs. 2%). The standardized infection ratio decreased from 1.83 to 0.92.
The culture of safety in the hospitals improved, but more modestly, in 10 of 12 areas that were measured over the study period.
The overall perception of patient safety improved from 49% to 53%, teamwork across different units improved from 49% to 54%, management and support for patient safety improved from 53% to 60%, and nonpunitive response to errors improved from 36% to 40%.
In addition, communication and openness improved from 50% to 53%, frequency of reported events improved from 51% to 60%, feedback and communication about errors improved from 52% to 59%, organizational learning and continuous improvement increased from 59% to 70%, teamwork within units improved from 68% to 75%, and expectations and actions by supervisors and managers to promote safety improved from 58% to 64%. Staff responses reflect agreement on improvement in the areas of issues of communication, feedback mechanisms, and teamwork, but the change in culture was not on the order of the SSI change.
The most common interventions to reduce SSIs were the use of reliable chlorhexidine wash or wipe before surgery/surgical prep; appropriate use of antibiotics with respect to selection, dosage, and timing; standardized postsurgical debriefing; and differentiating clean/dirty/clean in the use of anastomosis trays and closing trays.
One bundle component, the implementation of the standard operating room debrief, was found to be of particular value to participants. The investigators noted that debrief questions such as “What went well?” and “What needs to be improved?” had “encouraged new processes of thinking beyond first-order problem solving. The debrief challenge embraced by the teams emphasized that ‘bundles’ did not consist of only technical interventions [e.g. clean/dirty trays, chlorhexidine gluconate wipes in preop], but embedded culture interventions—new processes for problem solving.”
The study findings were limited by several factors, such as the use of public SSI data that were not audited for accuracy and the inability to monitor the reliability of the implementation of the various interventions, the researchers said. In addition, “In this current study, there was a change in SSI rates and a change in safety culture, but correlations between the two were negligible or weak for most domains of safety culture,” they noted. The question of sustainability of the SSI improvement without the concomitant staff support of culture change was not addressed by the investigators.
However, the results suggest that a 62% decrease is robust, and that for some hospitals with a low volume of colorectal cases, “teams could attend to iteratively reduce surgical harm beyond SSI,” the researchers wrote.
The study was supported in part by the AHRQ. Dr. Lin disclosed serving as a board member and as a paid independent contractor to the Hawaii Medical Service Association. Her coauthors had no financial conflicts to disclose.
SOURCE: Lin DM et al. J Am Coll Surg. 2018 May 18. doi: 10.1016/j.jamcollsurg.2018.04.031.
The Agency for Healthcare Research and Quality (AHRQ) designed the program to reduce surgical site infections (SSIs), which are harmful to patients and expensive for the health care system, wrote Della M. Lin, MD, of Johns Hopkins University, Baltimore, and the department of surgery at the University of Hawaii, Honolulu, and her colleagues.
In a study published in the Journal of the American College of Surgeons, the researchers reviewed data from a statewide intervention conducted at 15 hospitals in Hawaii from January 2013 to June 2015. The intervention included the Comprehensive Unit-based Safety Program and individualized interventions for each hospital to help reduce SSIs. The primary outcome was the number of colorectal SSIs. A secondary outcome of hospital safety culture was assessed using the AHRQ Hospital Survey on Patient Safety Culture. The participating hospitals ranged from a 25-bed critical-access hospital to a 533-bed academic medical center.
Overall, the colorectal SSI rate decreased significantly (from 12% to 5%) from the first quarter of 2013 to the second quarter of 2015, with a significant linear decrease over the study period. The rate of superficial SSIs decreased significantly, falling from 8% to 3%. However, the rate of deep SSIs was not significantly different before and after the intervention program (2% vs. 0%), nor was the organ space SSI rate (3% vs. 2%). The standardized infection ratio decreased from 1.83 to 0.92.
The culture of safety in the hospitals improved, but more modestly, in 10 of 12 areas that were measured over the study period.
The overall perception of patient safety improved from 49% to 53%, teamwork across different units improved from 49% to 54%, management and support for patient safety improved from 53% to 60%, and nonpunitive response to errors improved from 36% to 40%.
In addition, communication and openness improved from 50% to 53%, frequency of reported events improved from 51% to 60%, feedback and communication about errors improved from 52% to 59%, organizational learning and continuous improvement increased from 59% to 70%, teamwork within units improved from 68% to 75%, and expectations and actions by supervisors and managers to promote safety improved from 58% to 64%. Staff responses reflect agreement on improvement in the areas of issues of communication, feedback mechanisms, and teamwork, but the change in culture was not on the order of the SSI change.
The most common interventions to reduce SSIs were the use of reliable chlorhexidine wash or wipe before surgery/surgical prep; appropriate use of antibiotics with respect to selection, dosage, and timing; standardized postsurgical debriefing; and differentiating clean/dirty/clean in the use of anastomosis trays and closing trays.
One bundle component, the implementation of the standard operating room debrief, was found to be of particular value to participants. The investigators noted that debrief questions such as “What went well?” and “What needs to be improved?” had “encouraged new processes of thinking beyond first-order problem solving. The debrief challenge embraced by the teams emphasized that ‘bundles’ did not consist of only technical interventions [e.g. clean/dirty trays, chlorhexidine gluconate wipes in preop], but embedded culture interventions—new processes for problem solving.”
The study findings were limited by several factors, such as the use of public SSI data that were not audited for accuracy and the inability to monitor the reliability of the implementation of the various interventions, the researchers said. In addition, “In this current study, there was a change in SSI rates and a change in safety culture, but correlations between the two were negligible or weak for most domains of safety culture,” they noted. The question of sustainability of the SSI improvement without the concomitant staff support of culture change was not addressed by the investigators.
However, the results suggest that a 62% decrease is robust, and that for some hospitals with a low volume of colorectal cases, “teams could attend to iteratively reduce surgical harm beyond SSI,” the researchers wrote.
The study was supported in part by the AHRQ. Dr. Lin disclosed serving as a board member and as a paid independent contractor to the Hawaii Medical Service Association. Her coauthors had no financial conflicts to disclose.
SOURCE: Lin DM et al. J Am Coll Surg. 2018 May 18. doi: 10.1016/j.jamcollsurg.2018.04.031.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Key clinical point: Hospital participation in an Agency for Healthcare Research and Quality safety program improved safety culture and reduced surgical site infections.
Major finding: Surgical site infections among colorectal surgery patients decreased by 61.7% after the intervention.
Study details: The data come from a cohort study of 15 hospitals in Hawaii from January 2013 to June 2015.
Disclosures: The study was supported in part by the AHRQ. Dr. Lin disclosed serving as a board member and as a paid independent contractor to the Hawaii Medical Service Association. Her coauthors had no financial conflicts to disclose.
Source: Lin DM et al. J Am Coll Surg. 2018 May 18. doi: 10.1016/j.jamcollsurg.2018.04.031.
Blood type A linked to more-severe diarrhea
Diarrhea associated with enterotoxigenic Escherichia coli (ETEC) infection is more severe among individuals with blood type A, based on data from 106 adults exposed to the agent.
The reseachers speculate that the increased severity is related, in part, to the presence of an adhesin molecule known as EtpA, which binds to the surface of the cells and combines with blood group A glycans to promote a more severe infection.
“Our studies suggest that the many ETEC strains that produce the EtpA adhesin may be particularly well equipped to preferentially infect hosts who express A blood group antigen on mucosal surfaces,” wrote Pardeep Kumar, MD, of Washington University, Saint Louis, and his colleagues.
ETEC, associated with choleralike illness, remains a major cause of infectious diarrhea in developing countries. No current vaccine offers significant protection against it, but EtpA may be useful in vaccine development. “More recently discovered virulence factors and an improved understanding of ETEC microbial pathogenesis could offer additional avenues to protect those at highest risk for severe disease and uncover novel molecular targets for future vaccine development,” the researchers said.
In a study published in the Journal of Clinical Investigation, the researchers examined blood samples from 106 adults who had participated in previous human infection model studies. The volunteers were challenged with an ETEC strain known as H10407 that was originally isolated from a case of choleralike illness.
Diarrhea was more frequent among A blood type individuals, compared with other types. Individuals with B or O blood types were significantly more likely to have no diarrhea or mild diarrhea after the E. coli challenge, compared with type A individuals (44% vs. 19%).
Overall, significantly more individuals with A or AB blood types developed moderate to severe diarrhea, compared with those with B or O blood types (81% vs. 56%). In addition, significantly more individuals with blood type A needed early initiation of antibiotic therapy, compared with those with B or O blood types (72% vs. 43%).
The study findings were limited by several factors, including the use of higher levels of bacteria to cause the infection than a typical exposure in nature. Also, the volunteers were treated with antibiotics once they met the criteria for severe diarrhea.
The researchers also noted that other blood group A lectins in addition to EtpA may not have been identified.
“While our recent studies have potentially important clinical and [vaccinological] implications, further study of the relationship between blood group, disease severity, and antigen expression could guide and inform use of these antigens in vaccines,” they wrote.
The study was supported by funds from the Enteric Vaccine Initiative of PATH, the Department of Veterans Affairs, the National Institutes of Health, and the Digestive Diseases Research Core Center at Washington University School of Medicine, St. Louis. The researchers had no financial conflicts to disclose.
SOURCE: Kumar P et al. J Clin Invest. 2018 May 17. doi: 10.1172/JCI97659.
Diarrhea associated with enterotoxigenic Escherichia coli (ETEC) infection is more severe among individuals with blood type A, based on data from 106 adults exposed to the agent.
The reseachers speculate that the increased severity is related, in part, to the presence of an adhesin molecule known as EtpA, which binds to the surface of the cells and combines with blood group A glycans to promote a more severe infection.
“Our studies suggest that the many ETEC strains that produce the EtpA adhesin may be particularly well equipped to preferentially infect hosts who express A blood group antigen on mucosal surfaces,” wrote Pardeep Kumar, MD, of Washington University, Saint Louis, and his colleagues.
ETEC, associated with choleralike illness, remains a major cause of infectious diarrhea in developing countries. No current vaccine offers significant protection against it, but EtpA may be useful in vaccine development. “More recently discovered virulence factors and an improved understanding of ETEC microbial pathogenesis could offer additional avenues to protect those at highest risk for severe disease and uncover novel molecular targets for future vaccine development,” the researchers said.
In a study published in the Journal of Clinical Investigation, the researchers examined blood samples from 106 adults who had participated in previous human infection model studies. The volunteers were challenged with an ETEC strain known as H10407 that was originally isolated from a case of choleralike illness.
Diarrhea was more frequent among A blood type individuals, compared with other types. Individuals with B or O blood types were significantly more likely to have no diarrhea or mild diarrhea after the E. coli challenge, compared with type A individuals (44% vs. 19%).
Overall, significantly more individuals with A or AB blood types developed moderate to severe diarrhea, compared with those with B or O blood types (81% vs. 56%). In addition, significantly more individuals with blood type A needed early initiation of antibiotic therapy, compared with those with B or O blood types (72% vs. 43%).
The study findings were limited by several factors, including the use of higher levels of bacteria to cause the infection than a typical exposure in nature. Also, the volunteers were treated with antibiotics once they met the criteria for severe diarrhea.
The researchers also noted that other blood group A lectins in addition to EtpA may not have been identified.
“While our recent studies have potentially important clinical and [vaccinological] implications, further study of the relationship between blood group, disease severity, and antigen expression could guide and inform use of these antigens in vaccines,” they wrote.
The study was supported by funds from the Enteric Vaccine Initiative of PATH, the Department of Veterans Affairs, the National Institutes of Health, and the Digestive Diseases Research Core Center at Washington University School of Medicine, St. Louis. The researchers had no financial conflicts to disclose.
SOURCE: Kumar P et al. J Clin Invest. 2018 May 17. doi: 10.1172/JCI97659.
Diarrhea associated with enterotoxigenic Escherichia coli (ETEC) infection is more severe among individuals with blood type A, based on data from 106 adults exposed to the agent.
The reseachers speculate that the increased severity is related, in part, to the presence of an adhesin molecule known as EtpA, which binds to the surface of the cells and combines with blood group A glycans to promote a more severe infection.
“Our studies suggest that the many ETEC strains that produce the EtpA adhesin may be particularly well equipped to preferentially infect hosts who express A blood group antigen on mucosal surfaces,” wrote Pardeep Kumar, MD, of Washington University, Saint Louis, and his colleagues.
ETEC, associated with choleralike illness, remains a major cause of infectious diarrhea in developing countries. No current vaccine offers significant protection against it, but EtpA may be useful in vaccine development. “More recently discovered virulence factors and an improved understanding of ETEC microbial pathogenesis could offer additional avenues to protect those at highest risk for severe disease and uncover novel molecular targets for future vaccine development,” the researchers said.
In a study published in the Journal of Clinical Investigation, the researchers examined blood samples from 106 adults who had participated in previous human infection model studies. The volunteers were challenged with an ETEC strain known as H10407 that was originally isolated from a case of choleralike illness.
Diarrhea was more frequent among A blood type individuals, compared with other types. Individuals with B or O blood types were significantly more likely to have no diarrhea or mild diarrhea after the E. coli challenge, compared with type A individuals (44% vs. 19%).
Overall, significantly more individuals with A or AB blood types developed moderate to severe diarrhea, compared with those with B or O blood types (81% vs. 56%). In addition, significantly more individuals with blood type A needed early initiation of antibiotic therapy, compared with those with B or O blood types (72% vs. 43%).
The study findings were limited by several factors, including the use of higher levels of bacteria to cause the infection than a typical exposure in nature. Also, the volunteers were treated with antibiotics once they met the criteria for severe diarrhea.
The researchers also noted that other blood group A lectins in addition to EtpA may not have been identified.
“While our recent studies have potentially important clinical and [vaccinological] implications, further study of the relationship between blood group, disease severity, and antigen expression could guide and inform use of these antigens in vaccines,” they wrote.
The study was supported by funds from the Enteric Vaccine Initiative of PATH, the Department of Veterans Affairs, the National Institutes of Health, and the Digestive Diseases Research Core Center at Washington University School of Medicine, St. Louis. The researchers had no financial conflicts to disclose.
SOURCE: Kumar P et al. J Clin Invest. 2018 May 17. doi: 10.1172/JCI97659.
FROM THE JOURNAL OF CLINICAL INVESTIGATION
Key clinical point: Severe diarrhea was significantly more frequent in adults with an A blood type, compared with B or O types.
Major finding: The overall relative risk of moderate to severe diarrhea was 1.44 for A blood groups, compared with non-A blood groups.
Study details: The data come from 106 adult volunteers who had participated in previous human infection model studies.
Disclosures: The study was supported by funds from the PATH Enteric Vaccine Initiative, the Department of Veterans Affairs, the National Institutes of Health, and the Digestive Diseases Research Core Center at Washington University School of Medicine, St. Louis. The researchers had no financial conflicts to disclose.
Source: Kumar P et al. J Clin Invest. 2018 May 17; doi: 10.1172/JCI97659.
Specialty practices hire more physician assistants and nurse practitioners
based on data from a review of approximately 90% of physician practices in the United States.
The employment of advanced practice clinicians in primary care continues to grow, but their presence in specialty practices has not been well studied, wrote Grant R. Martsolf, PhD, of the University of Pittsburgh, and his colleagues. In a study published in JAMA Internal Medicine, the researchers used the proprietary SK&A data set to examine employment in specialty practices between 2008 and 2016.
Overall, 28% of all specialty practices employed advanced practice clinicians in 2016 – a 22% increase from 2008. Nearly half of multispecialty practices (49%) employed advanced practice clinicians, as did at least 25% of dermatology, cardiology, obstetrics-gynecology, orthopedic surgery, and gastroenterology practices.
Plastic surgery and ophthalmology practices were the least likely to employ advanced practice clinicians. Surgical practices were more likely to employ physician assistants than nurse practitioners, but the other specialty practices were more likely to employ NPs than PAs.
The growth in employment of advanced practice clinicians may be driven by factors such as economics and the expanding roles for advanced practice clinicians in specialty practice, the researchers said.
The findings were limited by the inclusion of outpatient providers only, and by the lack of information about the exact duties of advanced practice clinicians in each practice, the researchers noted. However, the results suggest that advanced practice clinicians will become even more prevalent in specialty care, and “future research will need to understand their contributions to access, quality, and value,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Martsolf GR et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.1515 .
based on data from a review of approximately 90% of physician practices in the United States.
The employment of advanced practice clinicians in primary care continues to grow, but their presence in specialty practices has not been well studied, wrote Grant R. Martsolf, PhD, of the University of Pittsburgh, and his colleagues. In a study published in JAMA Internal Medicine, the researchers used the proprietary SK&A data set to examine employment in specialty practices between 2008 and 2016.
Overall, 28% of all specialty practices employed advanced practice clinicians in 2016 – a 22% increase from 2008. Nearly half of multispecialty practices (49%) employed advanced practice clinicians, as did at least 25% of dermatology, cardiology, obstetrics-gynecology, orthopedic surgery, and gastroenterology practices.
Plastic surgery and ophthalmology practices were the least likely to employ advanced practice clinicians. Surgical practices were more likely to employ physician assistants than nurse practitioners, but the other specialty practices were more likely to employ NPs than PAs.
The growth in employment of advanced practice clinicians may be driven by factors such as economics and the expanding roles for advanced practice clinicians in specialty practice, the researchers said.
The findings were limited by the inclusion of outpatient providers only, and by the lack of information about the exact duties of advanced practice clinicians in each practice, the researchers noted. However, the results suggest that advanced practice clinicians will become even more prevalent in specialty care, and “future research will need to understand their contributions to access, quality, and value,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Martsolf GR et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.1515 .
based on data from a review of approximately 90% of physician practices in the United States.
The employment of advanced practice clinicians in primary care continues to grow, but their presence in specialty practices has not been well studied, wrote Grant R. Martsolf, PhD, of the University of Pittsburgh, and his colleagues. In a study published in JAMA Internal Medicine, the researchers used the proprietary SK&A data set to examine employment in specialty practices between 2008 and 2016.
Overall, 28% of all specialty practices employed advanced practice clinicians in 2016 – a 22% increase from 2008. Nearly half of multispecialty practices (49%) employed advanced practice clinicians, as did at least 25% of dermatology, cardiology, obstetrics-gynecology, orthopedic surgery, and gastroenterology practices.
Plastic surgery and ophthalmology practices were the least likely to employ advanced practice clinicians. Surgical practices were more likely to employ physician assistants than nurse practitioners, but the other specialty practices were more likely to employ NPs than PAs.
The growth in employment of advanced practice clinicians may be driven by factors such as economics and the expanding roles for advanced practice clinicians in specialty practice, the researchers said.
The findings were limited by the inclusion of outpatient providers only, and by the lack of information about the exact duties of advanced practice clinicians in each practice, the researchers noted. However, the results suggest that advanced practice clinicians will become even more prevalent in specialty care, and “future research will need to understand their contributions to access, quality, and value,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Martsolf GR et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.1515 .
FROM JAMA INTERNAL MEDICINE
Persistent providers sway parents to accept HPV vaccination
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
FROM PEDIATRICS
Key clinical point: A majority of unvaccinated adolescents received the HPV vaccine when clinicians engaged with hesitant parents.
Major finding: At 18 office visits when parents hesitated but doctors persisted, 17 adolescents received the HPV vaccine
Study details: The data come from audio recordings of 43 visits to six pediatric clinics in Dallas at which parents were unsure about HPV vaccination for their teens.
Disclosures: The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
Source: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
Subcutaneous buprenorpine rivals sublingual for opioid use disorder
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
FROM JAMA INTERNAL MEDICINE
Key clinical point: After 24 weeks, long-acting subcutaneous buprenorphine depot was noninferior to sublingual buprenorphine-naloxone for preventing opioid use.
Major finding: The proportion of opioid-negative urine samples was a statistically significant 6.7% higher in the subcutaneous group, compared with the sublingual group.
Study details: The data come from a randomized trial of 428 adults in treatment for opioid use disorder.
Disclosures: The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
Source: Lofwall M et al. JAMA Intern Med. 2018 May 14; doi: 10.1001/jamainternmed.2018.1052.
Cochrane report: HPV vaccine proves its worth in adolescent, young adult women
Two currently available human papillomavirus vaccines protect adolescents and young adult women without previous HPV disease from developing precancerous cervical lesions, according to data from more than 70,000 women followed for 8 years.
In a review published online by the Cochrane Library, Marc Arbyn, MD, of the Belgian Cancer Centre, Brussels, and his colleagues examined the effectiveness of two vaccines that target the HPV types 16 and 18, which account for most cases of cervical cancer. The researchers focused on the bivalent vaccine for HPV16 and HPV18 and the quadrivalent vaccine for HPV16, HPV18, and two additional HPV types associated with genital warts (HPV6 and HPV11). The review did not include data on the latest vaccine targeting nine HPV types because it has not been studied in a randomized, placebo-controlled trial.
The review comprised 26 studies and 73,428 women aged 15-45 years. The vaccine was most effective for young women aged 15-26 years.
The risk of serious adverse events was approximately 7% in control groups and vaccine groups across all ages (669 per 10,000 vs. 656 per 10,000, respectively). The mortality rate was 11 per 10,000 in control groups, compared with 14 per 10,000 in vaccine groups. The overall mortality was low, and no deaths reported in the studies were vaccine related, the researchers said, although mortality was greater in the vaccine groups among women older than 25 years.
The overall risk for precancerous lesions was not significantly different for women vaccinated between age 24 and 45 years versus unvaccinated women. However, the researchers found that the vaccines reduced the risk of precancerous lesions for HPV type 16 and 18 from 45 per 10, 000 to 14 per 10,000 in women aged 24 years and older who were previously negative for HPV 16 and 18.
The researchers found no significant impact on miscarriage rates, but they noted the need for additional research to examine the possible impact of vaccination on stillbirth and birth defects in children born to women who were vaccinated during pregnancy.
Several of the researchers received travel grants from GlaxoSmithKline or MSD-Sanofi-Pasteur.
SOURCE: Arbyn M et al. Cochrane Database Syst Rev. 2018. doi: 10.1002/14651858.CD009069.pub3.
Two currently available human papillomavirus vaccines protect adolescents and young adult women without previous HPV disease from developing precancerous cervical lesions, according to data from more than 70,000 women followed for 8 years.
In a review published online by the Cochrane Library, Marc Arbyn, MD, of the Belgian Cancer Centre, Brussels, and his colleagues examined the effectiveness of two vaccines that target the HPV types 16 and 18, which account for most cases of cervical cancer. The researchers focused on the bivalent vaccine for HPV16 and HPV18 and the quadrivalent vaccine for HPV16, HPV18, and two additional HPV types associated with genital warts (HPV6 and HPV11). The review did not include data on the latest vaccine targeting nine HPV types because it has not been studied in a randomized, placebo-controlled trial.
The review comprised 26 studies and 73,428 women aged 15-45 years. The vaccine was most effective for young women aged 15-26 years.
The risk of serious adverse events was approximately 7% in control groups and vaccine groups across all ages (669 per 10,000 vs. 656 per 10,000, respectively). The mortality rate was 11 per 10,000 in control groups, compared with 14 per 10,000 in vaccine groups. The overall mortality was low, and no deaths reported in the studies were vaccine related, the researchers said, although mortality was greater in the vaccine groups among women older than 25 years.
The overall risk for precancerous lesions was not significantly different for women vaccinated between age 24 and 45 years versus unvaccinated women. However, the researchers found that the vaccines reduced the risk of precancerous lesions for HPV type 16 and 18 from 45 per 10, 000 to 14 per 10,000 in women aged 24 years and older who were previously negative for HPV 16 and 18.
The researchers found no significant impact on miscarriage rates, but they noted the need for additional research to examine the possible impact of vaccination on stillbirth and birth defects in children born to women who were vaccinated during pregnancy.
Several of the researchers received travel grants from GlaxoSmithKline or MSD-Sanofi-Pasteur.
SOURCE: Arbyn M et al. Cochrane Database Syst Rev. 2018. doi: 10.1002/14651858.CD009069.pub3.
Two currently available human papillomavirus vaccines protect adolescents and young adult women without previous HPV disease from developing precancerous cervical lesions, according to data from more than 70,000 women followed for 8 years.
In a review published online by the Cochrane Library, Marc Arbyn, MD, of the Belgian Cancer Centre, Brussels, and his colleagues examined the effectiveness of two vaccines that target the HPV types 16 and 18, which account for most cases of cervical cancer. The researchers focused on the bivalent vaccine for HPV16 and HPV18 and the quadrivalent vaccine for HPV16, HPV18, and two additional HPV types associated with genital warts (HPV6 and HPV11). The review did not include data on the latest vaccine targeting nine HPV types because it has not been studied in a randomized, placebo-controlled trial.
The review comprised 26 studies and 73,428 women aged 15-45 years. The vaccine was most effective for young women aged 15-26 years.
The risk of serious adverse events was approximately 7% in control groups and vaccine groups across all ages (669 per 10,000 vs. 656 per 10,000, respectively). The mortality rate was 11 per 10,000 in control groups, compared with 14 per 10,000 in vaccine groups. The overall mortality was low, and no deaths reported in the studies were vaccine related, the researchers said, although mortality was greater in the vaccine groups among women older than 25 years.
The overall risk for precancerous lesions was not significantly different for women vaccinated between age 24 and 45 years versus unvaccinated women. However, the researchers found that the vaccines reduced the risk of precancerous lesions for HPV type 16 and 18 from 45 per 10, 000 to 14 per 10,000 in women aged 24 years and older who were previously negative for HPV 16 and 18.
The researchers found no significant impact on miscarriage rates, but they noted the need for additional research to examine the possible impact of vaccination on stillbirth and birth defects in children born to women who were vaccinated during pregnancy.
Several of the researchers received travel grants from GlaxoSmithKline or MSD-Sanofi-Pasteur.
SOURCE: Arbyn M et al. Cochrane Database Syst Rev. 2018. doi: 10.1002/14651858.CD009069.pub3.
FROM THE COCHRANE LIBRARY
Key clinical point:
Major finding: The vaccines reduced the risk of precancer caused by HPV16 and HPV18 from 341 per 10,000 to 157 per 10,000 (RR, 0.46).
Study details: The review was based on data from 26 studies including 73,428 women worldwide over 8 years.
Disclosures: The Cochrane Library sponsored the study. Several of the researchers received travel grants from GlaxoSmithKline or MSD-Sanofi-Pasteur.
Source: Arbyn M et al. Cochrane Database Syst Rev. 2018. doi: 10.1002/14651858.CD009069.pub3.
USPSTF advises against widespread prostate cancer screening
The USPSTF recommends that, to reduce the risk of false positives and unnecessary complications from prostate cancer screening and treatment, physicians and their male patients aged 55-69 years should review together the pros and cons.
Clinicians should not conduct prostate cancer screening in men aged 55-69 years who do not ask for it (level C recommendation), according to the USPSTF recommendations, published in JAMA, which also recommend against any prostate cancer screening for men aged 70 years and older (level D recommendation). The recommendations replace those from 2012, and upgrade the statement against routine screening from a D to a C.
“The change in recommendation grade further reflects new evidence about and increased use of active surveillance of low-risk prostate cancer, which may reduce the risk of subsequent harms from screening,” according to the USPSTF.
The recommendations apply to asymptomatic adult men in the general United States population with no previous diagnosis of prostate cancer, as well as those whose ethnicity or family history put them at increased risk of death from prostate cancer.
In the evidence report published in JAMA, Joshua J. Fenton, MD, professor in the department of family and community medicine of the University of California, Davis, Sacramento, and his colleagues reviewed 63 studies comprising 1,904,950 individuals. The researchers examined the findings for information including the effectiveness of PSA screening and the potential harms associated with both screening and cancer treatment if disease was identified.
Overdiagnosis of prostate cancer ranged from 21% to 50% for cancers detected by screening, and one randomized trial of more than 1,000 men found no significant reduction in mortality for prostatectomy or radiation therapy compared with active monitoring.
Overall, men randomized to PSA screening had no significant reduction in risk of prostate cancer mortality in trials from the United States or the United Kingdom, although data from a European trial showed a significant reduction. Complications requiring hospitalization occurred in 0.5%-1.6% of men who had biopsies after screening showed abnormal results.
The evidence review was limited by several factors including a lack of data on newer treatments such as cryotherapy and high-intensity focused ultrasound, the researchers noted.
However, the data support an individualized approach to PSA screening for prostate cancer, in which each man can weigh the potential risks and benefits of screening, according to the USPSTF.
The research was funded by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCE: Fenton J et al. JAMA. 2018;319(18):1914-31. and JAMA. 2018;319(18):1901-13.
The new USPSTF guidelines take a thoughtful approach to assessing the pros and cons of PSA-based prostate cancer screening and highlight the importance of identifying subgroups who could most benefit from screening and treatment, H. Ballentine Carter, MD, wrote in an accompanying editorial.
“Patients, together with their physicians, should decide whether prostate cancer screening is right for the patient. In this regard, primary care physicians have an important role in reducing the harms associated with screening and could consider a number of factors in this decision process,” he said.
In particular, Dr. Carter noted that men aged 55-69 years without multiple comorbidities would reap the greatest benefits from screening, while those aged 70 years and older would be more susceptible to the harm associated with testing and treatment and should be screened rarely. He also endorsed a 2- to 4-year screening interval to help reduce false-positive test results and overdiagnosis.
“By virtue of their relationship with patients, primary care physicians are in a unique position to help ensure that men diagnosed with favorable-risk disease (Gleason score 6 cancer grade on biopsy, and PSA level less than 10 ng/mL) are presenting a balanced message regarding management options,” with active surveillance as the preferred choice, he said. (JAMA. 2018. May 8;319[18]:1866-8).
Dr. Carter is Bernard L. Schwartz distinguished professor of urologic oncology and professor of urology at Johns Hopkins University School of Medicine, Baltimore, and had no financial conflicts to disclose.
The new USPSTF guidelines take a thoughtful approach to assessing the pros and cons of PSA-based prostate cancer screening and highlight the importance of identifying subgroups who could most benefit from screening and treatment, H. Ballentine Carter, MD, wrote in an accompanying editorial.
“Patients, together with their physicians, should decide whether prostate cancer screening is right for the patient. In this regard, primary care physicians have an important role in reducing the harms associated with screening and could consider a number of factors in this decision process,” he said.
In particular, Dr. Carter noted that men aged 55-69 years without multiple comorbidities would reap the greatest benefits from screening, while those aged 70 years and older would be more susceptible to the harm associated with testing and treatment and should be screened rarely. He also endorsed a 2- to 4-year screening interval to help reduce false-positive test results and overdiagnosis.
“By virtue of their relationship with patients, primary care physicians are in a unique position to help ensure that men diagnosed with favorable-risk disease (Gleason score 6 cancer grade on biopsy, and PSA level less than 10 ng/mL) are presenting a balanced message regarding management options,” with active surveillance as the preferred choice, he said. (JAMA. 2018. May 8;319[18]:1866-8).
Dr. Carter is Bernard L. Schwartz distinguished professor of urologic oncology and professor of urology at Johns Hopkins University School of Medicine, Baltimore, and had no financial conflicts to disclose.
The new USPSTF guidelines take a thoughtful approach to assessing the pros and cons of PSA-based prostate cancer screening and highlight the importance of identifying subgroups who could most benefit from screening and treatment, H. Ballentine Carter, MD, wrote in an accompanying editorial.
“Patients, together with their physicians, should decide whether prostate cancer screening is right for the patient. In this regard, primary care physicians have an important role in reducing the harms associated with screening and could consider a number of factors in this decision process,” he said.
In particular, Dr. Carter noted that men aged 55-69 years without multiple comorbidities would reap the greatest benefits from screening, while those aged 70 years and older would be more susceptible to the harm associated with testing and treatment and should be screened rarely. He also endorsed a 2- to 4-year screening interval to help reduce false-positive test results and overdiagnosis.
“By virtue of their relationship with patients, primary care physicians are in a unique position to help ensure that men diagnosed with favorable-risk disease (Gleason score 6 cancer grade on biopsy, and PSA level less than 10 ng/mL) are presenting a balanced message regarding management options,” with active surveillance as the preferred choice, he said. (JAMA. 2018. May 8;319[18]:1866-8).
Dr. Carter is Bernard L. Schwartz distinguished professor of urologic oncology and professor of urology at Johns Hopkins University School of Medicine, Baltimore, and had no financial conflicts to disclose.
The USPSTF recommends that, to reduce the risk of false positives and unnecessary complications from prostate cancer screening and treatment, physicians and their male patients aged 55-69 years should review together the pros and cons.
Clinicians should not conduct prostate cancer screening in men aged 55-69 years who do not ask for it (level C recommendation), according to the USPSTF recommendations, published in JAMA, which also recommend against any prostate cancer screening for men aged 70 years and older (level D recommendation). The recommendations replace those from 2012, and upgrade the statement against routine screening from a D to a C.
“The change in recommendation grade further reflects new evidence about and increased use of active surveillance of low-risk prostate cancer, which may reduce the risk of subsequent harms from screening,” according to the USPSTF.
The recommendations apply to asymptomatic adult men in the general United States population with no previous diagnosis of prostate cancer, as well as those whose ethnicity or family history put them at increased risk of death from prostate cancer.
In the evidence report published in JAMA, Joshua J. Fenton, MD, professor in the department of family and community medicine of the University of California, Davis, Sacramento, and his colleagues reviewed 63 studies comprising 1,904,950 individuals. The researchers examined the findings for information including the effectiveness of PSA screening and the potential harms associated with both screening and cancer treatment if disease was identified.
Overdiagnosis of prostate cancer ranged from 21% to 50% for cancers detected by screening, and one randomized trial of more than 1,000 men found no significant reduction in mortality for prostatectomy or radiation therapy compared with active monitoring.
Overall, men randomized to PSA screening had no significant reduction in risk of prostate cancer mortality in trials from the United States or the United Kingdom, although data from a European trial showed a significant reduction. Complications requiring hospitalization occurred in 0.5%-1.6% of men who had biopsies after screening showed abnormal results.
The evidence review was limited by several factors including a lack of data on newer treatments such as cryotherapy and high-intensity focused ultrasound, the researchers noted.
However, the data support an individualized approach to PSA screening for prostate cancer, in which each man can weigh the potential risks and benefits of screening, according to the USPSTF.
The research was funded by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCE: Fenton J et al. JAMA. 2018;319(18):1914-31. and JAMA. 2018;319(18):1901-13.
The USPSTF recommends that, to reduce the risk of false positives and unnecessary complications from prostate cancer screening and treatment, physicians and their male patients aged 55-69 years should review together the pros and cons.
Clinicians should not conduct prostate cancer screening in men aged 55-69 years who do not ask for it (level C recommendation), according to the USPSTF recommendations, published in JAMA, which also recommend against any prostate cancer screening for men aged 70 years and older (level D recommendation). The recommendations replace those from 2012, and upgrade the statement against routine screening from a D to a C.
“The change in recommendation grade further reflects new evidence about and increased use of active surveillance of low-risk prostate cancer, which may reduce the risk of subsequent harms from screening,” according to the USPSTF.
The recommendations apply to asymptomatic adult men in the general United States population with no previous diagnosis of prostate cancer, as well as those whose ethnicity or family history put them at increased risk of death from prostate cancer.
In the evidence report published in JAMA, Joshua J. Fenton, MD, professor in the department of family and community medicine of the University of California, Davis, Sacramento, and his colleagues reviewed 63 studies comprising 1,904,950 individuals. The researchers examined the findings for information including the effectiveness of PSA screening and the potential harms associated with both screening and cancer treatment if disease was identified.
Overdiagnosis of prostate cancer ranged from 21% to 50% for cancers detected by screening, and one randomized trial of more than 1,000 men found no significant reduction in mortality for prostatectomy or radiation therapy compared with active monitoring.
Overall, men randomized to PSA screening had no significant reduction in risk of prostate cancer mortality in trials from the United States or the United Kingdom, although data from a European trial showed a significant reduction. Complications requiring hospitalization occurred in 0.5%-1.6% of men who had biopsies after screening showed abnormal results.
The evidence review was limited by several factors including a lack of data on newer treatments such as cryotherapy and high-intensity focused ultrasound, the researchers noted.
However, the data support an individualized approach to PSA screening for prostate cancer, in which each man can weigh the potential risks and benefits of screening, according to the USPSTF.
The research was funded by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCE: Fenton J et al. JAMA. 2018;319(18):1914-31. and JAMA. 2018;319(18):1901-13.
Key clinical point: PSA-based screening for prostate cancer in men aged 55-69 years has limited benefits and significant risks.
Major finding: Overdiagnosis occurred in approximately 21%-50% of cancers identified during PSA screening.
Study details: The evidence report was based on 63 studies including 1.9 million men.
Disclosures: The research was funded by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
Source: JAMA. 2018;319(18):1901-13. Fenton J et al. JAMA. 2018;319(18):1914-31.
Interferon-gamma release assay trumps tuberculin skin test in school-aged children
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
FROM PEDIATRICS
Key clinical point:
Major finding: Sensitivity was 96% for IGRA versus 83% for TST among children aged 5-18 years.
Study details: The data come from TB patients aged 18 years and younger enrolled in the California TB registry during 2010-2015.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test; Dr. Kay and the other investigators had no financial conflicts to disclose.
Source: Kay A et al. Pediatrics. 2018 May 4. doi: 10. 1542/ peds. 2017- 3918.