Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Surgical site infections among colorectal surgery patients in Hawaii decreased by approximately 62% after hospital participation in a national safety program.

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.

Surgical site infections among colorectal surgery patients in Hawaii decreased by approximately 62% after hospital participation in a national safety program.

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.

Surgical site infections among colorectal surgery patients in Hawaii decreased by approximately 62% after hospital participation in a national safety program.

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.

Background: Literature regarding patient satisfaction often focuses on nonspecific recommendations to improve patient-centered communication. There is lack of guidance on concrete advice for clinicians, particularly with regard to how a provider’s responses to different patient requests are received.

Study design: Cross-sectional study.

Setting: An outpatient family medicine clinic.

Synopsis: Patient requests from 1,141 patients visiting the University of California, Davis, Family Medicine Clinic were sampled. The study examined clinician’s approval or denial of patients’ requests for referrals, pain medications, other new medicines, laboratory testing, radiology testing, or other testing and the patients’ reported satisfaction of the clinician.

Clinician denial of particular requests was associated with decreased patient satisfaction. Specifically, a 19.75% drop for referral, 10.72% drop for pain medication, 20.36% drop for other new medications, and 9.19% drop for laboratory test. This study did not examine other potential reasons for decreased satisfaction.

Bottom line: Clinicians can better understand how to communicate in a patient-centered manner by understanding that not all patient requests are perceived as equal.

Citation: Jerant A et al. Association of clinical denial of patient requests with patient satisfaction. JAMA Intern Med. 2018 Jan 1;178(1):85-91.

Dr. Shaffie is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Literature regarding patient satisfaction often focuses on nonspecific recommendations to improve patient-centered communication. There is lack of guidance on concrete advice for clinicians, particularly with regard to how a provider’s responses to different patient requests are received.

Study design: Cross-sectional study.

Setting: An outpatient family medicine clinic.

Synopsis: Patient requests from 1,141 patients visiting the University of California, Davis, Family Medicine Clinic were sampled. The study examined clinician’s approval or denial of patients’ requests for referrals, pain medications, other new medicines, laboratory testing, radiology testing, or other testing and the patients’ reported satisfaction of the clinician.

Clinician denial of particular requests was associated with decreased patient satisfaction. Specifically, a 19.75% drop for referral, 10.72% drop for pain medication, 20.36% drop for other new medications, and 9.19% drop for laboratory test. This study did not examine other potential reasons for decreased satisfaction.

Bottom line: Clinicians can better understand how to communicate in a patient-centered manner by understanding that not all patient requests are perceived as equal.

Citation: Jerant A et al. Association of clinical denial of patient requests with patient satisfaction. JAMA Intern Med. 2018 Jan 1;178(1):85-91.

Dr. Shaffie is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Literature regarding patient satisfaction often focuses on nonspecific recommendations to improve patient-centered communication. There is lack of guidance on concrete advice for clinicians, particularly with regard to how a provider’s responses to different patient requests are received.

Study design: Cross-sectional study.

Setting: An outpatient family medicine clinic.

Synopsis: Patient requests from 1,141 patients visiting the University of California, Davis, Family Medicine Clinic were sampled. The study examined clinician’s approval or denial of patients’ requests for referrals, pain medications, other new medicines, laboratory testing, radiology testing, or other testing and the patients’ reported satisfaction of the clinician.

Clinician denial of particular requests was associated with decreased patient satisfaction. Specifically, a 19.75% drop for referral, 10.72% drop for pain medication, 20.36% drop for other new medications, and 9.19% drop for laboratory test. This study did not examine other potential reasons for decreased satisfaction.

Bottom line: Clinicians can better understand how to communicate in a patient-centered manner by understanding that not all patient requests are perceived as equal.

Citation: Jerant A et al. Association of clinical denial of patient requests with patient satisfaction. JAMA Intern Med. 2018 Jan 1;178(1):85-91.

Dr. Shaffie is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).

Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.

Bruce Jancin/MDedge News

“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.

“There is a strong signal that physiology [FFR/iFR]-guided PCI is superior over angiography-guided PCI for mortality, restenosis, and stent thrombosis up to 10 years” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.

Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
 

FAME 2

Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.

The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.

The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.

Bruce Jancin/MDedge News

Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”

Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.

“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.

ORBITA revisited

ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.

However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.

Bruce Jancin/MDedge News

Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”

SCAAR

Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.

Bruce Jancin/MDedge News

He reported no financial conflicts of interest regarding his study.

Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.

Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.

Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.

bjancin@mdedge.com

PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).

Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.

Bruce Jancin/MDedge News

“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.

“There is a strong signal that physiology [FFR/iFR]-guided PCI is superior over angiography-guided PCI for mortality, restenosis, and stent thrombosis up to 10 years” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.

Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
 

FAME 2

Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.

The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.

The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.

Bruce Jancin/MDedge News

Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”

Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.

“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.

ORBITA revisited

ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.

However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.

Bruce Jancin/MDedge News

Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”

SCAAR

Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.

Bruce Jancin/MDedge News

He reported no financial conflicts of interest regarding his study.

Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.

Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.

Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.

bjancin@mdedge.com

PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).

Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.

Bruce Jancin/MDedge News

“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.

“There is a strong signal that physiology [FFR/iFR]-guided PCI is superior over angiography-guided PCI for mortality, restenosis, and stent thrombosis up to 10 years” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.

Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
 

FAME 2

Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.

The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.

The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.

Bruce Jancin/MDedge News

Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”

Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.

“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.

ORBITA revisited

ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.

However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.

Bruce Jancin/MDedge News

Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”

SCAAR

Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.

Bruce Jancin/MDedge News

He reported no financial conflicts of interest regarding his study.

Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.

Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.

Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.

bjancin@mdedge.com

A study suggests that delirium in older adults is a postoperative variable that should be included in surgical quality registries, outcome measures, and assessment of hospital performance.

Lead author Julia R. Berian, MD, of the University of Chicago Medical Center and her colleagues wrote, “Postoperative delirium has been associated with mortality, morbidity, prolonged length of stay, and increased costs of care. Furthermore, postoperative delirium may be associated with long-term cognitive and functional decline. However, postoperative delirium has not been incorporated as an outcome measure into major surgical quality registries. Approximately one-third of hospitalized delirium is believed to be preventable, making postoperative delirium an ideal target for surgical quality improvement efforts,” Dr. Berian and her colleagues reported in the Annals of Surgery.

Study authors noted that screening for postoperative delirium in older adults is likely in the best interests of patients. However, they also mentioned that such screening may identify cases of postoperative delirium that were previously unrecognized, resulting in higher rates. In addition, the inclusion of only ACS NSQIP hospitals and the voluntary participation may mean a biased dataset. No one delirium prevention intervention was implemented across the hospitals and so the study doesn’t indicate why some hospitals are more successful than are others. Chart-based identification of patients who have delirium needs further study to assess validity.

Authors concluded that one solution may be to “standardize and consistently employ delirium screening in high-risk patients across hospitals, as has been advocated by a coalition of interdisciplinary experts in geriatric care.”

This project is funded in part by a grant from the John A. Hartford Foundation. The authors declare no conflict of interests.

SOURCE: Berlan JR et al. Ann Surg. 2017 July 24. doi: 10.1097/SLA.0000000000002436

A study suggests that delirium in older adults is a postoperative variable that should be included in surgical quality registries, outcome measures, and assessment of hospital performance.

Lead author Julia R. Berian, MD, of the University of Chicago Medical Center and her colleagues wrote, “Postoperative delirium has been associated with mortality, morbidity, prolonged length of stay, and increased costs of care. Furthermore, postoperative delirium may be associated with long-term cognitive and functional decline. However, postoperative delirium has not been incorporated as an outcome measure into major surgical quality registries. Approximately one-third of hospitalized delirium is believed to be preventable, making postoperative delirium an ideal target for surgical quality improvement efforts,” Dr. Berian and her colleagues reported in the Annals of Surgery.

Study authors noted that screening for postoperative delirium in older adults is likely in the best interests of patients. However, they also mentioned that such screening may identify cases of postoperative delirium that were previously unrecognized, resulting in higher rates. In addition, the inclusion of only ACS NSQIP hospitals and the voluntary participation may mean a biased dataset. No one delirium prevention intervention was implemented across the hospitals and so the study doesn’t indicate why some hospitals are more successful than are others. Chart-based identification of patients who have delirium needs further study to assess validity.

Authors concluded that one solution may be to “standardize and consistently employ delirium screening in high-risk patients across hospitals, as has been advocated by a coalition of interdisciplinary experts in geriatric care.”

This project is funded in part by a grant from the John A. Hartford Foundation. The authors declare no conflict of interests.

SOURCE: Berlan JR et al. Ann Surg. 2017 July 24. doi: 10.1097/SLA.0000000000002436

A study suggests that delirium in older adults is a postoperative variable that should be included in surgical quality registries, outcome measures, and assessment of hospital performance.

Lead author Julia R. Berian, MD, of the University of Chicago Medical Center and her colleagues wrote, “Postoperative delirium has been associated with mortality, morbidity, prolonged length of stay, and increased costs of care. Furthermore, postoperative delirium may be associated with long-term cognitive and functional decline. However, postoperative delirium has not been incorporated as an outcome measure into major surgical quality registries. Approximately one-third of hospitalized delirium is believed to be preventable, making postoperative delirium an ideal target for surgical quality improvement efforts,” Dr. Berian and her colleagues reported in the Annals of Surgery.

Study authors noted that screening for postoperative delirium in older adults is likely in the best interests of patients. However, they also mentioned that such screening may identify cases of postoperative delirium that were previously unrecognized, resulting in higher rates. In addition, the inclusion of only ACS NSQIP hospitals and the voluntary participation may mean a biased dataset. No one delirium prevention intervention was implemented across the hospitals and so the study doesn’t indicate why some hospitals are more successful than are others. Chart-based identification of patients who have delirium needs further study to assess validity.

Authors concluded that one solution may be to “standardize and consistently employ delirium screening in high-risk patients across hospitals, as has been advocated by a coalition of interdisciplinary experts in geriatric care.”

This project is funded in part by a grant from the John A. Hartford Foundation. The authors declare no conflict of interests.

SOURCE: Berlan JR et al. Ann Surg. 2017 July 24. doi: 10.1097/SLA.0000000000002436

Jake clearly needed a biopsy.

When I suggested that we find out what that new growth on his cheek was, he responded with fear. “Do you really need to test it?” he asked. Then he proposed an alternative.

“I had another spot last year,” he said. “This European doctor I saw in somebody’s home put a special black salve on it, and it went away.”

“Who was this doctor?” I asked.

“At the time, I was a raw vegan,” he said. “One of our group members gave me the doctor’s name. He has a big reputation in Europe. He treated people locally in people’s living rooms.”

“Do you recall his name?” I asked him.

Jake didn’t. But I did.

Three years ago, a frightened, middle-aged woman named Josie came to see me with ugly scarring all over her face.

• Fear. They think they have cancer and are afraid to find out.
• Suspicion. They don’t trust doctors.
• People they hang with tell them to. Some groups harbor a suspicious, even hostile stance toward conventional medicine, convinced that its principles are unnatural and its practitioners are more concerned with profit and prestige than with the good of their patients.

Those who hold such beliefs, like various conspiracy theorists, span the political and social spectrum, from left to right, and they’ve been around forever.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

Jake clearly needed a biopsy.

When I suggested that we find out what that new growth on his cheek was, he responded with fear. “Do you really need to test it?” he asked. Then he proposed an alternative.

“I had another spot last year,” he said. “This European doctor I saw in somebody’s home put a special black salve on it, and it went away.”

“Who was this doctor?” I asked.

“At the time, I was a raw vegan,” he said. “One of our group members gave me the doctor’s name. He has a big reputation in Europe. He treated people locally in people’s living rooms.”

“Do you recall his name?” I asked him.

Jake didn’t. But I did.

Three years ago, a frightened, middle-aged woman named Josie came to see me with ugly scarring all over her face.

• Fear. They think they have cancer and are afraid to find out.
• Suspicion. They don’t trust doctors.
• People they hang with tell them to. Some groups harbor a suspicious, even hostile stance toward conventional medicine, convinced that its principles are unnatural and its practitioners are more concerned with profit and prestige than with the good of their patients.

Those who hold such beliefs, like various conspiracy theorists, span the political and social spectrum, from left to right, and they’ve been around forever.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

Jake clearly needed a biopsy.

When I suggested that we find out what that new growth on his cheek was, he responded with fear. “Do you really need to test it?” he asked. Then he proposed an alternative.

“I had another spot last year,” he said. “This European doctor I saw in somebody’s home put a special black salve on it, and it went away.”

“Who was this doctor?” I asked.

“At the time, I was a raw vegan,” he said. “One of our group members gave me the doctor’s name. He has a big reputation in Europe. He treated people locally in people’s living rooms.”

“Do you recall his name?” I asked him.

Jake didn’t. But I did.

Three years ago, a frightened, middle-aged woman named Josie came to see me with ugly scarring all over her face.

• Fear. They think they have cancer and are afraid to find out.
• Suspicion. They don’t trust doctors.
• People they hang with tell them to. Some groups harbor a suspicious, even hostile stance toward conventional medicine, convinced that its principles are unnatural and its practitioners are more concerned with profit and prestige than with the good of their patients.

Those who hold such beliefs, like various conspiracy theorists, span the political and social spectrum, from left to right, and they’ve been around forever.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire. Also today, uptake of lung cancer screening is exceedingly low, financial incentives led to increased smoking cessation, and Congress passes the “right to try” bill.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire. Also today, uptake of lung cancer screening is exceedingly low, financial incentives led to increased smoking cessation, and Congress passes the “right to try” bill.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire. Also today, uptake of lung cancer screening is exceedingly low, financial incentives led to increased smoking cessation, and Congress passes the “right to try” bill.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

A reanalysis of 2 National Institutes of Health (NIH)-funded studies refutes the conclusions of PROMISE (Promoting Maternal and Infant Survival Everywhere), which found tenofovir disoproxil fumarate (TDF) combination treatment raised the risk of adverse outcomes.

The PROMISE study compared several treatments in pregnant women with HIV in India and Africa. According to those researchers, women on TDF regimens were twice as likely as those on zidovudine to have a very preterm infant, and their infants were more likely to die within the first 2 weeks. 

Those results surprised the current researchers, given that other, earlier studies had found TDF combinations safe for use during pregnancy. In fact, the World Health Organization recommends that all adults with HIV, including pregnant women, receive TDF combination therapy.

In the current study, NIH researchers compared outcomes from 2 US studies, reviewing records on more than 4,600 infants born to 3,847 women. The women were on either a combination regimen including zidovudine or 1 containing TDF.

The researchers found no significant differences in the risk of preterm birth or low birth weight, nor did they find any significant difference in severe birth outcomes, including infant death, in the first 2 weeks. “Notably,” they add, comparing women on zidovudine combination treatment with TDF/emtricitabine/atazanavir/ritonavir, the researchers found the TDF group had a 10% lower chance of preterm birth, low birth weight, and infant death.

Source:

National Institutes of Health. https://www.nih.gov/news-events/news-releases/anti-hiv-drug-combination-does-not-increase-preterm-birth-risk-study-suggests. Published April 25, 2018. Accessed May 24, 2018.

A reanalysis of 2 National Institutes of Health (NIH)-funded studies refutes the conclusions of PROMISE (Promoting Maternal and Infant Survival Everywhere), which found tenofovir disoproxil fumarate (TDF) combination treatment raised the risk of adverse outcomes.

The PROMISE study compared several treatments in pregnant women with HIV in India and Africa. According to those researchers, women on TDF regimens were twice as likely as those on zidovudine to have a very preterm infant, and their infants were more likely to die within the first 2 weeks. 

Those results surprised the current researchers, given that other, earlier studies had found TDF combinations safe for use during pregnancy. In fact, the World Health Organization recommends that all adults with HIV, including pregnant women, receive TDF combination therapy.

In the current study, NIH researchers compared outcomes from 2 US studies, reviewing records on more than 4,600 infants born to 3,847 women. The women were on either a combination regimen including zidovudine or 1 containing TDF.

The researchers found no significant differences in the risk of preterm birth or low birth weight, nor did they find any significant difference in severe birth outcomes, including infant death, in the first 2 weeks. “Notably,” they add, comparing women on zidovudine combination treatment with TDF/emtricitabine/atazanavir/ritonavir, the researchers found the TDF group had a 10% lower chance of preterm birth, low birth weight, and infant death.

Source:

National Institutes of Health. https://www.nih.gov/news-events/news-releases/anti-hiv-drug-combination-does-not-increase-preterm-birth-risk-study-suggests. Published April 25, 2018. Accessed May 24, 2018.

A reanalysis of 2 National Institutes of Health (NIH)-funded studies refutes the conclusions of PROMISE (Promoting Maternal and Infant Survival Everywhere), which found tenofovir disoproxil fumarate (TDF) combination treatment raised the risk of adverse outcomes.

The PROMISE study compared several treatments in pregnant women with HIV in India and Africa. According to those researchers, women on TDF regimens were twice as likely as those on zidovudine to have a very preterm infant, and their infants were more likely to die within the first 2 weeks. 

Those results surprised the current researchers, given that other, earlier studies had found TDF combinations safe for use during pregnancy. In fact, the World Health Organization recommends that all adults with HIV, including pregnant women, receive TDF combination therapy.

In the current study, NIH researchers compared outcomes from 2 US studies, reviewing records on more than 4,600 infants born to 3,847 women. The women were on either a combination regimen including zidovudine or 1 containing TDF.

The researchers found no significant differences in the risk of preterm birth or low birth weight, nor did they find any significant difference in severe birth outcomes, including infant death, in the first 2 weeks. “Notably,” they add, comparing women on zidovudine combination treatment with TDF/emtricitabine/atazanavir/ritonavir, the researchers found the TDF group had a 10% lower chance of preterm birth, low birth weight, and infant death.

Source:

National Institutes of Health. https://www.nih.gov/news-events/news-releases/anti-hiv-drug-combination-does-not-increase-preterm-birth-risk-study-suggests. Published April 25, 2018. Accessed May 24, 2018.

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com