Micrograph showing MM

Preclinical research suggests an AKT inhibitor could be effective against multiple myeloma (MM).

The inhibitor, HS1793, is a derivative of the antioxidant compound resveratrol.

Investigators found that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in MM cells.

HS1793 was cytotoxic to MM cells in a mouse model of human metastatic myeloma and in human MM cells in vitro.

Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues reported these results in Cancer Letters.

“AKT is frequently activated in MM cells, and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They had screened 400 compounds and identified HS1793 as the most promising AKT inhibitor. Experiments suggested that HS1793 inhibits AKT activation by interfering with the interaction between AKT and its promoter, HSP90.

HS1793 exhibited antimyeloma activity in human MM cell lines. The investigators said this appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In additional experiments, the team found that HS1793’s inhibition of AKT/HSP90 interaction results in cell death by suppressing NF-κB signaling. HS1793-induced cell death was caused by the direct inhibition of AKT that, in turn, suppressed NF-κB activation.

The investigators found that HS1793 “dramatically decreased” lytic skull and femur lesions in a mouse model of MM metastatic to bone. And mice that received HS1793 had superior survival, when compared to mice that received vehicle control.

The investigators also showed that HS1793 was cytotoxic to MM cells but not normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” the authors wrote.

This research was supported by grants from the Korean government. The investigators reported no potential conflicts of interest.

Micrograph showing MM

Preclinical research suggests an AKT inhibitor could be effective against multiple myeloma (MM).

The inhibitor, HS1793, is a derivative of the antioxidant compound resveratrol.

Investigators found that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in MM cells.

HS1793 was cytotoxic to MM cells in a mouse model of human metastatic myeloma and in human MM cells in vitro.

Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues reported these results in Cancer Letters.

“AKT is frequently activated in MM cells, and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They had screened 400 compounds and identified HS1793 as the most promising AKT inhibitor. Experiments suggested that HS1793 inhibits AKT activation by interfering with the interaction between AKT and its promoter, HSP90.

HS1793 exhibited antimyeloma activity in human MM cell lines. The investigators said this appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In additional experiments, the team found that HS1793’s inhibition of AKT/HSP90 interaction results in cell death by suppressing NF-κB signaling. HS1793-induced cell death was caused by the direct inhibition of AKT that, in turn, suppressed NF-κB activation.

The investigators found that HS1793 “dramatically decreased” lytic skull and femur lesions in a mouse model of MM metastatic to bone. And mice that received HS1793 had superior survival, when compared to mice that received vehicle control.

The investigators also showed that HS1793 was cytotoxic to MM cells but not normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” the authors wrote.

This research was supported by grants from the Korean government. The investigators reported no potential conflicts of interest.

Micrograph showing MM

Preclinical research suggests an AKT inhibitor could be effective against multiple myeloma (MM).

The inhibitor, HS1793, is a derivative of the antioxidant compound resveratrol.

Investigators found that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in MM cells.

HS1793 was cytotoxic to MM cells in a mouse model of human metastatic myeloma and in human MM cells in vitro.

Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues reported these results in Cancer Letters.

“AKT is frequently activated in MM cells, and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They had screened 400 compounds and identified HS1793 as the most promising AKT inhibitor. Experiments suggested that HS1793 inhibits AKT activation by interfering with the interaction between AKT and its promoter, HSP90.

HS1793 exhibited antimyeloma activity in human MM cell lines. The investigators said this appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In additional experiments, the team found that HS1793’s inhibition of AKT/HSP90 interaction results in cell death by suppressing NF-κB signaling. HS1793-induced cell death was caused by the direct inhibition of AKT that, in turn, suppressed NF-κB activation.

The investigators found that HS1793 “dramatically decreased” lytic skull and femur lesions in a mouse model of MM metastatic to bone. And mice that received HS1793 had superior survival, when compared to mice that received vehicle control.

The investigators also showed that HS1793 was cytotoxic to MM cells but not normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” the authors wrote.

This research was supported by grants from the Korean government. The investigators reported no potential conflicts of interest.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.

Your practice manager, on a quest to reduce expenses, asks whether your practice could reduce the amount of money spent on gloves for procedures. How do you reply?

The effect of a small difference spread over a large number of events can be sizable. For example, the added cost of using sterile, as opposed to nonsterile, gloves for minor procedures is relatively modest and certainly worthwhile if the sterile gloves reduce the number of surgical site infections (SSIs). However, if there is no difference in SSIs, the extra cost becomes a large unnecessary expense, given the volume of minor procedures performed.

The decision to use sterile gloves often stems from habit, product availability, or perceived benefit of fewer SSIs.² Providers’ choice of gloves varies widely, despite some evidence comparing sterile and nonsterile gloves.^3-5

STUDY SUMMARY

Sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 RCTs and observational (prospective or retrospective) studies compared infection rates using sterile versus nonsterile gloves in 11,071 unique patients. The methods used in the review followed the Cochrane collaboration guidelines.⁶ Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. A total of 512 publications were reviewed for inclusion; 14 met the criteria but one study was removed due to incomplete data, leaving 13 trials with a total of 11,071 patients for the analysis. In the RCTs, 1,360 patients were randomly assigned to treatment with sterile gloves and 1,381 to treatment with nonsterile gloves as the intervention. In the prospective or retrospective observational trials, 4,680 patients were treated with sterile gloves, and 3,650 were treated with nonsterile gloves. Heterogeneity was low. Of note, the researchers performed a subgroup analysis on nine studies (4 RCTs and 5 observational studies) involving only cutaneous surgeries; these represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile and nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR], 1.06). There was also no difference in infection rate in the subgroup analysis (2.2% vs 2.2%, respectively; RR, 1.02) or an analysis limited to only RCTs.

WHAT’S NEW

Highest-quality evidence shows no difference

This systematic review found no difference in SSI rates when using sterile versus nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

Continue to: CAVEATS

 

 

CAVEATS

Risk for bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk for bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Providers may worry about potential medicolegal ramifications from this change.¹ Lastly, some providers may prefer the fit and feel of sterile gloves for their procedures.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[8]:507-508).

Your practice manager, on a quest to reduce expenses, asks whether your practice could reduce the amount of money spent on gloves for procedures. How do you reply?

The effect of a small difference spread over a large number of events can be sizable. For example, the added cost of using sterile, as opposed to nonsterile, gloves for minor procedures is relatively modest and certainly worthwhile if the sterile gloves reduce the number of surgical site infections (SSIs). However, if there is no difference in SSIs, the extra cost becomes a large unnecessary expense, given the volume of minor procedures performed.

The decision to use sterile gloves often stems from habit, product availability, or perceived benefit of fewer SSIs.² Providers’ choice of gloves varies widely, despite some evidence comparing sterile and nonsterile gloves.^3-5

STUDY SUMMARY

Sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 RCTs and observational (prospective or retrospective) studies compared infection rates using sterile versus nonsterile gloves in 11,071 unique patients. The methods used in the review followed the Cochrane collaboration guidelines.⁶ Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. A total of 512 publications were reviewed for inclusion; 14 met the criteria but one study was removed due to incomplete data, leaving 13 trials with a total of 11,071 patients for the analysis. In the RCTs, 1,360 patients were randomly assigned to treatment with sterile gloves and 1,381 to treatment with nonsterile gloves as the intervention. In the prospective or retrospective observational trials, 4,680 patients were treated with sterile gloves, and 3,650 were treated with nonsterile gloves. Heterogeneity was low. Of note, the researchers performed a subgroup analysis on nine studies (4 RCTs and 5 observational studies) involving only cutaneous surgeries; these represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile and nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR], 1.06). There was also no difference in infection rate in the subgroup analysis (2.2% vs 2.2%, respectively; RR, 1.02) or an analysis limited to only RCTs.

WHAT’S NEW

Highest-quality evidence shows no difference

This systematic review found no difference in SSI rates when using sterile versus nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

Continue to: CAVEATS

 

 

CAVEATS

Risk for bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk for bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Providers may worry about potential medicolegal ramifications from this change.¹ Lastly, some providers may prefer the fit and feel of sterile gloves for their procedures.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[8]:507-508).

Your practice manager, on a quest to reduce expenses, asks whether your practice could reduce the amount of money spent on gloves for procedures. How do you reply?

The effect of a small difference spread over a large number of events can be sizable. For example, the added cost of using sterile, as opposed to nonsterile, gloves for minor procedures is relatively modest and certainly worthwhile if the sterile gloves reduce the number of surgical site infections (SSIs). However, if there is no difference in SSIs, the extra cost becomes a large unnecessary expense, given the volume of minor procedures performed.

The decision to use sterile gloves often stems from habit, product availability, or perceived benefit of fewer SSIs.² Providers’ choice of gloves varies widely, despite some evidence comparing sterile and nonsterile gloves.^3-5

STUDY SUMMARY

Sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 RCTs and observational (prospective or retrospective) studies compared infection rates using sterile versus nonsterile gloves in 11,071 unique patients. The methods used in the review followed the Cochrane collaboration guidelines.⁶ Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. A total of 512 publications were reviewed for inclusion; 14 met the criteria but one study was removed due to incomplete data, leaving 13 trials with a total of 11,071 patients for the analysis. In the RCTs, 1,360 patients were randomly assigned to treatment with sterile gloves and 1,381 to treatment with nonsterile gloves as the intervention. In the prospective or retrospective observational trials, 4,680 patients were treated with sterile gloves, and 3,650 were treated with nonsterile gloves. Heterogeneity was low. Of note, the researchers performed a subgroup analysis on nine studies (4 RCTs and 5 observational studies) involving only cutaneous surgeries; these represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile and nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR], 1.06). There was also no difference in infection rate in the subgroup analysis (2.2% vs 2.2%, respectively; RR, 1.02) or an analysis limited to only RCTs.

WHAT’S NEW

Highest-quality evidence shows no difference

This systematic review found no difference in SSI rates when using sterile versus nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

Continue to: CAVEATS

 

 

CAVEATS

Risk for bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk for bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Providers may worry about potential medicolegal ramifications from this change.¹ Lastly, some providers may prefer the fit and feel of sterile gloves for their procedures.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[8]:507-508).

Opioid prescribers will need to be mindful of a new, expanded Risk Evaluation and Mitigation Strategy issued Sept. 18 by the Food and Drug Administration, covering immediate-release opioid analgesics used in the outpatient setting. The strategy also applies to extended-release and long-acting opioids, which have been subject to REMS since 2012.

The new REMS program requires for the first time that training be made available to health care providers who are involved in pain management. For the purposes of this REMS program, the training is not limited to just the prescriber, but includes nurses and pharmacists.

REMS educational materials are now required to cover broader information about pain management, including alternatives to opioids for pain management.

The FDA said it is in the process of approving a new label for opioids that will contain information about health care provider education that is now a part of the REMS.

“Our new effort is aimed at arming providers with the most current and comprehensive information on the appropriate management of pain,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Appropriate prescribing practices and education are important steps that we are prioritizing to help address the human and financial toll of this crisis.”

Dr. Gottlieb added that the goal of the new REMS is to help prescribers with the latest evidence on the appropriate amount of doses that should be prescribed for a given condition and that the “aim is to reduce overall dispensing as a way to further reduce exposure to these drugs. Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids and fostering rational prescribing to enable appropriate access to those patients who have legitimate medical need for these medicines.”

The FDA also approved a new guidance document that includes updated educational content.

[email protected]

Opioid prescribers will need to be mindful of a new, expanded Risk Evaluation and Mitigation Strategy issued Sept. 18 by the Food and Drug Administration, covering immediate-release opioid analgesics used in the outpatient setting. The strategy also applies to extended-release and long-acting opioids, which have been subject to REMS since 2012.

The new REMS program requires for the first time that training be made available to health care providers who are involved in pain management. For the purposes of this REMS program, the training is not limited to just the prescriber, but includes nurses and pharmacists.

REMS educational materials are now required to cover broader information about pain management, including alternatives to opioids for pain management.

The FDA said it is in the process of approving a new label for opioids that will contain information about health care provider education that is now a part of the REMS.

“Our new effort is aimed at arming providers with the most current and comprehensive information on the appropriate management of pain,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Appropriate prescribing practices and education are important steps that we are prioritizing to help address the human and financial toll of this crisis.”

Dr. Gottlieb added that the goal of the new REMS is to help prescribers with the latest evidence on the appropriate amount of doses that should be prescribed for a given condition and that the “aim is to reduce overall dispensing as a way to further reduce exposure to these drugs. Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids and fostering rational prescribing to enable appropriate access to those patients who have legitimate medical need for these medicines.”

The FDA also approved a new guidance document that includes updated educational content.

[email protected]

Opioid prescribers will need to be mindful of a new, expanded Risk Evaluation and Mitigation Strategy issued Sept. 18 by the Food and Drug Administration, covering immediate-release opioid analgesics used in the outpatient setting. The strategy also applies to extended-release and long-acting opioids, which have been subject to REMS since 2012.

The new REMS program requires for the first time that training be made available to health care providers who are involved in pain management. For the purposes of this REMS program, the training is not limited to just the prescriber, but includes nurses and pharmacists.

REMS educational materials are now required to cover broader information about pain management, including alternatives to opioids for pain management.

The FDA said it is in the process of approving a new label for opioids that will contain information about health care provider education that is now a part of the REMS.

“Our new effort is aimed at arming providers with the most current and comprehensive information on the appropriate management of pain,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Appropriate prescribing practices and education are important steps that we are prioritizing to help address the human and financial toll of this crisis.”

Dr. Gottlieb added that the goal of the new REMS is to help prescribers with the latest evidence on the appropriate amount of doses that should be prescribed for a given condition and that the “aim is to reduce overall dispensing as a way to further reduce exposure to these drugs. Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids and fostering rational prescribing to enable appropriate access to those patients who have legitimate medical need for these medicines.”

The FDA also approved a new guidance document that includes updated educational content.

[email protected]

The Centers for Medicare and Medicaid Services is test driving a new quality measurement model that pushes hospital readmissions measures out from 30 to 90 days.

DAJ/Thinkstock

Previous research has identified vascular surgery as having twice as high rates of 90-day readmissions, compared with 30-day readmissions (Am J Manag Care. 2014;20[9]:e432-e438), and this could prove problematic in light of the CMS pilot project currently underway, according to Donald E. Fry, MD, of MPA Healthcare Solutions, Chicago, and his colleagues.

They performed a study that found a high level of adverse outcomes for common vascular procedures and that there was a significant variability in risk-adjusted outcomes among best- and poorest-performing hospitals in all major vascular procedures, indicating that a large opportunity exists for improvement in results.

Medicare’s value-based care Readmissions Reduction Model developed financial penalties for hospitals that fail to achieve acceptable performance scores, and in doing so shifted some of the financial risks of care to the providers based on a 30-day readmission model. In contrast, the pilot Bundled Payments for Care Improvement (BPCI) Advanced Program, which the CMS plans to launch in October 2018, will follow a 90-day period of postoperative care as its duration of financial accountability.

“While BPCI Advanced, has, until now, focused upon orthopedics, cardiovascular procedures, and high-volume medical admissions areas, it is anticipated that vascular surgery will be included in the future,” according to the investigators. Therefore, the researchers performed an in-depth analysis to examine the 90-day outcomes of common vascular surgeries across hospitals as a prelude to the vascular surgery field having to potentially confront this new CMS model (Surgery 2018 Jun 22 doi: 10.1016/j.surg.2018.03.025).

Dr. Fry and his colleagues used the Medicare Limited Data Set for 2012-2014 to follow the outcomes of major vascular surgery beginning with the inpatient stay and on through 90 days of postoperative care. A pool of more than 500 aggregated and individual candidate risk factors, including age and sex, was used in model development, based upon data from 359 hospitals with 10,815 patients in the Medicare Limited Data Set.

The researchers examined the risk-adjusted outcomes of four major groupings of vascular surgery procedures: elective open aortic; open peripheral vascular procedures; endovascular aortic; and percutaneous angioplasty procedures.

They found that the total adverse-outcome rate (AO) was 27.8% for open aortic procedures, 31.5% for open peripheral vascular procedures, 19.6% for endovascular aortic procedures, and 36.4% for percutaneous angioplasty procedures. The difference in risk-adjusted adverse-outcome rates between the best- and the poorest- performing deciles was 32.2% for open aortic procedures, 29.5% for open peripheral vascular procedures, 21.5% for endovascular aortic procedures, and 37.1% for percutaneous angioplasty procedures.

The model determined significant risk factors (P less than .001) for inpatient death (including malnutrition, intestinal ischemia, supplemental oxygen, and age greater than or equal to 85 years); prolonged length of stay (including supplemental oxygen, peritoneal adhesions, and chronic lung obstructive disease); 90-day postdischarge death (including heart failure, chronic infection, psychosis, and primary head/neck cancer); and 90-day postdischarge readmission (malnutrition, chronic obstructive lung disease, upper aerodigestive tract cancer, and skin ulceration) for these procedures.

For all cases, the total 90-day postdischarge mortality rate exceeded the inpatient death rate, and readmissions were the major driver of the total AO. They found that 22% of all patients readmitted across the entire 90-day interval had not seen a physician for follow-up after discharge. [This] “begs the question of whether more frequent physician or physician-extender follow-up can reduce this AO,” according to Dr. Fry and his colleagues. “Importantly, first readmissions during days 31-90 following discharge were almost as common as those occurring during the initial 30 days. Over 20% of total readmissions were subsequently repeat events during the 90-day interval,” they added.

They also found that the variability in risk-adjusted outcomes among the best and poorest performing hospitals was over 20% in all of the major vascular procedures and indicates a large opportunity for improvement in results.

“Understanding variables associated with higher risk can be used as a decision support tool to identify which patients will need increased vigilance to avoid AOs. Identification of very high risk may become a consideration in the assessment of the appropriateness of the surgical intervention. If providers know their outcomes and those outcomes are benchmarked against the whole population of hospitals, then clinical performance can be improved by specific care redesign initiatives,” the researchers concluded.

Dr. Fry is executive vice president of MPA Healthcare Solutions, which funded the research.

[email protected]

SOURCE: Fry DE et al. Surgery 2018 Jun 22. doi: 10.1016/j.surg.2018.03.025.

The Centers for Medicare and Medicaid Services is test driving a new quality measurement model that pushes hospital readmissions measures out from 30 to 90 days.

DAJ/Thinkstock

Previous research has identified vascular surgery as having twice as high rates of 90-day readmissions, compared with 30-day readmissions (Am J Manag Care. 2014;20[9]:e432-e438), and this could prove problematic in light of the CMS pilot project currently underway, according to Donald E. Fry, MD, of MPA Healthcare Solutions, Chicago, and his colleagues.

They performed a study that found a high level of adverse outcomes for common vascular procedures and that there was a significant variability in risk-adjusted outcomes among best- and poorest-performing hospitals in all major vascular procedures, indicating that a large opportunity exists for improvement in results.

Medicare’s value-based care Readmissions Reduction Model developed financial penalties for hospitals that fail to achieve acceptable performance scores, and in doing so shifted some of the financial risks of care to the providers based on a 30-day readmission model. In contrast, the pilot Bundled Payments for Care Improvement (BPCI) Advanced Program, which the CMS plans to launch in October 2018, will follow a 90-day period of postoperative care as its duration of financial accountability.

“While BPCI Advanced, has, until now, focused upon orthopedics, cardiovascular procedures, and high-volume medical admissions areas, it is anticipated that vascular surgery will be included in the future,” according to the investigators. Therefore, the researchers performed an in-depth analysis to examine the 90-day outcomes of common vascular surgeries across hospitals as a prelude to the vascular surgery field having to potentially confront this new CMS model (Surgery 2018 Jun 22 doi: 10.1016/j.surg.2018.03.025).

Dr. Fry and his colleagues used the Medicare Limited Data Set for 2012-2014 to follow the outcomes of major vascular surgery beginning with the inpatient stay and on through 90 days of postoperative care. A pool of more than 500 aggregated and individual candidate risk factors, including age and sex, was used in model development, based upon data from 359 hospitals with 10,815 patients in the Medicare Limited Data Set.

The researchers examined the risk-adjusted outcomes of four major groupings of vascular surgery procedures: elective open aortic; open peripheral vascular procedures; endovascular aortic; and percutaneous angioplasty procedures.

They found that the total adverse-outcome rate (AO) was 27.8% for open aortic procedures, 31.5% for open peripheral vascular procedures, 19.6% for endovascular aortic procedures, and 36.4% for percutaneous angioplasty procedures. The difference in risk-adjusted adverse-outcome rates between the best- and the poorest- performing deciles was 32.2% for open aortic procedures, 29.5% for open peripheral vascular procedures, 21.5% for endovascular aortic procedures, and 37.1% for percutaneous angioplasty procedures.

The model determined significant risk factors (P less than .001) for inpatient death (including malnutrition, intestinal ischemia, supplemental oxygen, and age greater than or equal to 85 years); prolonged length of stay (including supplemental oxygen, peritoneal adhesions, and chronic lung obstructive disease); 90-day postdischarge death (including heart failure, chronic infection, psychosis, and primary head/neck cancer); and 90-day postdischarge readmission (malnutrition, chronic obstructive lung disease, upper aerodigestive tract cancer, and skin ulceration) for these procedures.

For all cases, the total 90-day postdischarge mortality rate exceeded the inpatient death rate, and readmissions were the major driver of the total AO. They found that 22% of all patients readmitted across the entire 90-day interval had not seen a physician for follow-up after discharge. [This] “begs the question of whether more frequent physician or physician-extender follow-up can reduce this AO,” according to Dr. Fry and his colleagues. “Importantly, first readmissions during days 31-90 following discharge were almost as common as those occurring during the initial 30 days. Over 20% of total readmissions were subsequently repeat events during the 90-day interval,” they added.

They also found that the variability in risk-adjusted outcomes among the best and poorest performing hospitals was over 20% in all of the major vascular procedures and indicates a large opportunity for improvement in results.

“Understanding variables associated with higher risk can be used as a decision support tool to identify which patients will need increased vigilance to avoid AOs. Identification of very high risk may become a consideration in the assessment of the appropriateness of the surgical intervention. If providers know their outcomes and those outcomes are benchmarked against the whole population of hospitals, then clinical performance can be improved by specific care redesign initiatives,” the researchers concluded.

Dr. Fry is executive vice president of MPA Healthcare Solutions, which funded the research.

[email protected]

SOURCE: Fry DE et al. Surgery 2018 Jun 22. doi: 10.1016/j.surg.2018.03.025.

The Centers for Medicare and Medicaid Services is test driving a new quality measurement model that pushes hospital readmissions measures out from 30 to 90 days.

DAJ/Thinkstock

Previous research has identified vascular surgery as having twice as high rates of 90-day readmissions, compared with 30-day readmissions (Am J Manag Care. 2014;20[9]:e432-e438), and this could prove problematic in light of the CMS pilot project currently underway, according to Donald E. Fry, MD, of MPA Healthcare Solutions, Chicago, and his colleagues.

They performed a study that found a high level of adverse outcomes for common vascular procedures and that there was a significant variability in risk-adjusted outcomes among best- and poorest-performing hospitals in all major vascular procedures, indicating that a large opportunity exists for improvement in results.

Medicare’s value-based care Readmissions Reduction Model developed financial penalties for hospitals that fail to achieve acceptable performance scores, and in doing so shifted some of the financial risks of care to the providers based on a 30-day readmission model. In contrast, the pilot Bundled Payments for Care Improvement (BPCI) Advanced Program, which the CMS plans to launch in October 2018, will follow a 90-day period of postoperative care as its duration of financial accountability.

“While BPCI Advanced, has, until now, focused upon orthopedics, cardiovascular procedures, and high-volume medical admissions areas, it is anticipated that vascular surgery will be included in the future,” according to the investigators. Therefore, the researchers performed an in-depth analysis to examine the 90-day outcomes of common vascular surgeries across hospitals as a prelude to the vascular surgery field having to potentially confront this new CMS model (Surgery 2018 Jun 22 doi: 10.1016/j.surg.2018.03.025).

Dr. Fry and his colleagues used the Medicare Limited Data Set for 2012-2014 to follow the outcomes of major vascular surgery beginning with the inpatient stay and on through 90 days of postoperative care. A pool of more than 500 aggregated and individual candidate risk factors, including age and sex, was used in model development, based upon data from 359 hospitals with 10,815 patients in the Medicare Limited Data Set.

The researchers examined the risk-adjusted outcomes of four major groupings of vascular surgery procedures: elective open aortic; open peripheral vascular procedures; endovascular aortic; and percutaneous angioplasty procedures.

They found that the total adverse-outcome rate (AO) was 27.8% for open aortic procedures, 31.5% for open peripheral vascular procedures, 19.6% for endovascular aortic procedures, and 36.4% for percutaneous angioplasty procedures. The difference in risk-adjusted adverse-outcome rates between the best- and the poorest- performing deciles was 32.2% for open aortic procedures, 29.5% for open peripheral vascular procedures, 21.5% for endovascular aortic procedures, and 37.1% for percutaneous angioplasty procedures.

The model determined significant risk factors (P less than .001) for inpatient death (including malnutrition, intestinal ischemia, supplemental oxygen, and age greater than or equal to 85 years); prolonged length of stay (including supplemental oxygen, peritoneal adhesions, and chronic lung obstructive disease); 90-day postdischarge death (including heart failure, chronic infection, psychosis, and primary head/neck cancer); and 90-day postdischarge readmission (malnutrition, chronic obstructive lung disease, upper aerodigestive tract cancer, and skin ulceration) for these procedures.

For all cases, the total 90-day postdischarge mortality rate exceeded the inpatient death rate, and readmissions were the major driver of the total AO. They found that 22% of all patients readmitted across the entire 90-day interval had not seen a physician for follow-up after discharge. [This] “begs the question of whether more frequent physician or physician-extender follow-up can reduce this AO,” according to Dr. Fry and his colleagues. “Importantly, first readmissions during days 31-90 following discharge were almost as common as those occurring during the initial 30 days. Over 20% of total readmissions were subsequently repeat events during the 90-day interval,” they added.

They also found that the variability in risk-adjusted outcomes among the best and poorest performing hospitals was over 20% in all of the major vascular procedures and indicates a large opportunity for improvement in results.

“Understanding variables associated with higher risk can be used as a decision support tool to identify which patients will need increased vigilance to avoid AOs. Identification of very high risk may become a consideration in the assessment of the appropriateness of the surgical intervention. If providers know their outcomes and those outcomes are benchmarked against the whole population of hospitals, then clinical performance can be improved by specific care redesign initiatives,” the researchers concluded.

Dr. Fry is executive vice president of MPA Healthcare Solutions, which funded the research.

[email protected]

SOURCE: Fry DE et al. Surgery 2018 Jun 22. doi: 10.1016/j.surg.2018.03.025.

MUNICH – The largest-ever study of spontaneous coronary artery dissection shows that, while most affected patients do well with conservative management, two independent risk factors identify subgroups at high risk for in-hospital and 30-day major adverse events.

Bruce Jancin/MDedge News

Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.

CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.

SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.

CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.

In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.

Of note, one-third of patients had no cardiovascular risk factors.

The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.

Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.

The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.

Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.

“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.

Bruce Jancin/MDedge News

Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”

“Are you doing that in your practice?” asked Dr. Serruys.

“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”

Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.

“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
 

The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.

[email protected]

MUNICH – The largest-ever study of spontaneous coronary artery dissection shows that, while most affected patients do well with conservative management, two independent risk factors identify subgroups at high risk for in-hospital and 30-day major adverse events.

Bruce Jancin/MDedge News

Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.

CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.

SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.

CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.

In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.

Of note, one-third of patients had no cardiovascular risk factors.

The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.

Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.

The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.

Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.

“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.

Bruce Jancin/MDedge News

Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”

“Are you doing that in your practice?” asked Dr. Serruys.

“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”

Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.

“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
 

The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.

[email protected]

MUNICH – The largest-ever study of spontaneous coronary artery dissection shows that, while most affected patients do well with conservative management, two independent risk factors identify subgroups at high risk for in-hospital and 30-day major adverse events.

Bruce Jancin/MDedge News

Women whose spontaneous coronary artery dissection (SCAD) occurred during the peripartum period were at 2.8-fold increased risk of in-hospital major adverse events in a multivariate analysis, while those with a background connective tissue disorder were at 8.7-fold increased risk for major adverse cardiovascular events within 30 days of hospitalization in the Canadian SCAD (CanSCAD) study, Jacqueline Saw, MD, reported at the annual congress of the European Society of Cardiology.

CanSCAD is an ongoing, rigorous, prospective, multicenter, observational study of 750 patients with SCAD documented on angiography and confirmed in a core lab. To put the study in perspective, the worldwide medical literature published over the last decade contains fewer than 1,300 other cases of this seriously underdiagnosed, poorly understood disorder, noted Dr. Saw, CanSCAD principal investigator and a cardiologist at the University of British Columbia, Vancouver. Because much remains unclear about SCAD, a condition mistakenly considered to be rare in the past, the Canadian study was undertaken to shed light on predisposing and precipitating factors, optimal management, and clinical outcomes. Although Dr. Saw could present only the in-hospital and 30-day outcomes, follow-up will continue at 6, 12, 24, and 36 months.

SCAD is a nontraumatic, noniatrogenic, nonatherosclerotic separation of the coronary artery wall by intramural hematoma, creating a false lumen which compresses the true arterial lumen. This compromises blood flow with resultant myocardial ischemia or infarction. Intimal tear may or may not be present.

CanSCAD underscored that this is predominantly a disease affecting relatively young women: 89% of SCAD participants were female, 55% of whom were postmenopausal. The mean age at presentation was 52 years, and only 9% of subjects were older than age 65. Seventy percent of subjects presented with non–ST-elevation MI, the other 30% with STEMI. The predominant symptom was chest pain in 92% of patients. The average length of hospital stay was 4 days.

In terms of precipitating factors, half of patients cited high or severe emotional stress, with 41% of subjects scoring 20 or higher on the Perceived Stress Scale. About 30% of patients cited unusually intense physical stress, such as lifting more than 50 pounds, as a precipitating factor.

Of note, one-third of patients had no cardiovascular risk factors.

The in-hospital major adverse event rate – a composite of all-cause mortality, stroke, recurrent MI, cardiogenic shock, heart failure, cardiac arrest, repeat or unplanned revascularization, and heart transplantation – was 8.8%. Mortality through 1 month was reassuringly low, at 0.1%. Nonetheless, 4.9% of patients experienced recurrent symptoms necessitating emergency room visits within 30 days post discharge, and 2.5% required hospitalization because of their chest pain.

Patients who presented with SCAD during the peripartum period were more severely affected. Although they accounted for only 4.5% of subjects, their in-hospital major adverse event rate was 20.6%, compared with 8.2% in the others. They had a 17.6% prevalence of a left ventricular ejection fraction below 35%, as did only 3.1% of patients without peripartum SCAD. They were more than twice as likely to have elevated cardiac troponin levels. Moreover, peripartum SCAD was independently associated with a 2.9-fold increased risk of major adverse cardiovascular events at 30 days, a composite of all-cause mortality, stroke, recurrent MI, heart failure, or revascularization.

The other independent predictor of 30-day major adverse cardiovascular events in a multivariate logistic regression analysis was having a connective tissue disorder, present in 3.6% of participants.

Management was conservative, with no percutaneous coronary intervention used in 84% of patients. Outcomes were worse in the subgroup who underwent PCI, but Dr. Saw cautioned against making much of that.

“Keep in mind that the patients who undergo PCI are typically the higher-risk cohort with ongoing ischemia and chest pain, so there will be some bias there,” according to the cardiologist.

Bruce Jancin/MDedge News

Session chair Patrick W. Serruys, MD, of Erasmus University, Rotterdam, the Netherlands, commented, “It seems like there is a critical period of 30 days, more or less, and beyond that time the situation can be considered as settled and a wait-and-see attitude is fine. It looked like patients with peripartum dissection or connective tissue disease should potentially be kept in hospital for at least 15 days, and maybe 30 days, because I see your cumulative adverse event curve plateauing around 15 days.”

“Are you doing that in your practice?” asked Dr. Serruys.

“It’s true that conservatively managed patients should remain in hospital for typically about 4 days. For patients with a high-risk presentation we do advocate staying in hospital for longer periods,” Dr. Saw replied. “It would be great to keep them for 15 days, although typically if their chest pain has settled by 10 days they can be discharged home.”

Audience members were eager to hear her recommendations regarding dual-antiplatelet therapy. She explained that in her practice patients are generally discharged on aspirin and clopidogrel and typically continue the clopidogrel for at least a month.

“When we follow them in the office at 1 month, if their chest pain has settled, we would discontinue DAPT,” Dr. Saw said.
 

The ongoing CanSCAD study is sponsored by the Canadian Institutes of Health Research, the Stroke Foundation of Canada, the National Institutes of Health, Abbott Vascular, Boston Scientific, AstraZeneca, and Servier. Dr. Saw reported serving as a consultant to Abbott Vascular and Boston Scientific.

[email protected]

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SAN DIEGO – When it comes to treating pigmented lesions with laser and light, not all devices are created equal.

Victor Ross, MD, turns to the Q-switched alexandrite laser as his device of choice for most pigmented lesions. “I also use the Q-switched 1,064 nm Nd:YAG and sometimes use the Q-switched 532 nm Nd:YAG, particularly for lighter-skinned patients with lighter lesions,” he said at the annual Masters of Aesthetics Symposium.

Compared with long-pulsed devices, the Q-switched 532 nm neodymium:YAG laser is better for one-time pigment reduction and better for treating lighter pigmented spots, yet it’s associated with a higher risk of postinflammatory hyperpigmentation and short-term crusting. “The Q-switched 532 nm Nd:YAG laser will even treat very tight lentigines, but vascular effects tend to cause an immediate bright red color and more postinflammatory hyperpigmentation,” said Dr. Ross, director of laser and cosmetic dermatology at the Scripps Clinic in San Diego. He cautioned that the Q-switched 532 nm Nd:YAG laser may cause prolonged redness on the legs and arms of some patients. “This laser is best reserved for lighter skinned patients with very light lentigines – the brisk purpura can prove distasteful short term for cosmetic patients,” he said. “For darker lentigines, I prefer the IPL [intense pulse light], KTP [potassium titanyl phosphate] laser, or Q-switched alexandrite lasers.”

Meanwhile, treating pigmented lesions treated with long-pulse IPL, KTP, and pulsed dye lasers show less risk of postinflammatory hyperpigmentation and better coverage rates. However, they are sensitive to background color and are less likely to achieve complete one-time removal. The first treatment works the best because the “low hanging fruit” (darker lesions) will do well, he said.

For clinicians looking to improve their skills in treating pigmented lesions with lasers, Dr. Ross recommended using a skin meter such as Cynosure’s Skintel Melanin Reader, which measures the real-time pigment of skin. “You measure the pigment, and it gives you a reading,” he said. “It gives you a recommended setting based on the hand piece and the pulse duration.”

Melasma remains a difficult condition to treat with laser and light. In fact, Dr. Ross joked that he wouldn’t mind if the words “He cured melasma” graced his tombstone one day. “I have been treating melasma patients for 29 years now, and I’m not closer to a cure than when I started out,” he said. “I’ve tried lots of things. In my defense, I’ve made more people better than worse.”

His approach to treating melasma is to begin with a KTP laser or a gentle IPL if discrete lesions or telangiectasia are present. Next, he applies hydroquinone followed by a series of treatment sessions with the Q-switched Nd:YAG laser or a conservative fractional laser. “This tends to induce remission, but is associated with a high rate of relapse,” he said.

Dr. Ross disclosed having research and financial ties to numerous pharmaceutical and device companies.

[email protected]

SAN DIEGO – When it comes to treating pigmented lesions with laser and light, not all devices are created equal.

Victor Ross, MD, turns to the Q-switched alexandrite laser as his device of choice for most pigmented lesions. “I also use the Q-switched 1,064 nm Nd:YAG and sometimes use the Q-switched 532 nm Nd:YAG, particularly for lighter-skinned patients with lighter lesions,” he said at the annual Masters of Aesthetics Symposium.

Compared with long-pulsed devices, the Q-switched 532 nm neodymium:YAG laser is better for one-time pigment reduction and better for treating lighter pigmented spots, yet it’s associated with a higher risk of postinflammatory hyperpigmentation and short-term crusting. “The Q-switched 532 nm Nd:YAG laser will even treat very tight lentigines, but vascular effects tend to cause an immediate bright red color and more postinflammatory hyperpigmentation,” said Dr. Ross, director of laser and cosmetic dermatology at the Scripps Clinic in San Diego. He cautioned that the Q-switched 532 nm Nd:YAG laser may cause prolonged redness on the legs and arms of some patients. “This laser is best reserved for lighter skinned patients with very light lentigines – the brisk purpura can prove distasteful short term for cosmetic patients,” he said. “For darker lentigines, I prefer the IPL [intense pulse light], KTP [potassium titanyl phosphate] laser, or Q-switched alexandrite lasers.”

Meanwhile, treating pigmented lesions treated with long-pulse IPL, KTP, and pulsed dye lasers show less risk of postinflammatory hyperpigmentation and better coverage rates. However, they are sensitive to background color and are less likely to achieve complete one-time removal. The first treatment works the best because the “low hanging fruit” (darker lesions) will do well, he said.

For clinicians looking to improve their skills in treating pigmented lesions with lasers, Dr. Ross recommended using a skin meter such as Cynosure’s Skintel Melanin Reader, which measures the real-time pigment of skin. “You measure the pigment, and it gives you a reading,” he said. “It gives you a recommended setting based on the hand piece and the pulse duration.”

Melasma remains a difficult condition to treat with laser and light. In fact, Dr. Ross joked that he wouldn’t mind if the words “He cured melasma” graced his tombstone one day. “I have been treating melasma patients for 29 years now, and I’m not closer to a cure than when I started out,” he said. “I’ve tried lots of things. In my defense, I’ve made more people better than worse.”

His approach to treating melasma is to begin with a KTP laser or a gentle IPL if discrete lesions or telangiectasia are present. Next, he applies hydroquinone followed by a series of treatment sessions with the Q-switched Nd:YAG laser or a conservative fractional laser. “This tends to induce remission, but is associated with a high rate of relapse,” he said.

Dr. Ross disclosed having research and financial ties to numerous pharmaceutical and device companies.

[email protected]

SAN DIEGO – When it comes to treating pigmented lesions with laser and light, not all devices are created equal.

Victor Ross, MD, turns to the Q-switched alexandrite laser as his device of choice for most pigmented lesions. “I also use the Q-switched 1,064 nm Nd:YAG and sometimes use the Q-switched 532 nm Nd:YAG, particularly for lighter-skinned patients with lighter lesions,” he said at the annual Masters of Aesthetics Symposium.

Compared with long-pulsed devices, the Q-switched 532 nm neodymium:YAG laser is better for one-time pigment reduction and better for treating lighter pigmented spots, yet it’s associated with a higher risk of postinflammatory hyperpigmentation and short-term crusting. “The Q-switched 532 nm Nd:YAG laser will even treat very tight lentigines, but vascular effects tend to cause an immediate bright red color and more postinflammatory hyperpigmentation,” said Dr. Ross, director of laser and cosmetic dermatology at the Scripps Clinic in San Diego. He cautioned that the Q-switched 532 nm Nd:YAG laser may cause prolonged redness on the legs and arms of some patients. “This laser is best reserved for lighter skinned patients with very light lentigines – the brisk purpura can prove distasteful short term for cosmetic patients,” he said. “For darker lentigines, I prefer the IPL [intense pulse light], KTP [potassium titanyl phosphate] laser, or Q-switched alexandrite lasers.”

Meanwhile, treating pigmented lesions treated with long-pulse IPL, KTP, and pulsed dye lasers show less risk of postinflammatory hyperpigmentation and better coverage rates. However, they are sensitive to background color and are less likely to achieve complete one-time removal. The first treatment works the best because the “low hanging fruit” (darker lesions) will do well, he said.

For clinicians looking to improve their skills in treating pigmented lesions with lasers, Dr. Ross recommended using a skin meter such as Cynosure’s Skintel Melanin Reader, which measures the real-time pigment of skin. “You measure the pigment, and it gives you a reading,” he said. “It gives you a recommended setting based on the hand piece and the pulse duration.”

Melasma remains a difficult condition to treat with laser and light. In fact, Dr. Ross joked that he wouldn’t mind if the words “He cured melasma” graced his tombstone one day. “I have been treating melasma patients for 29 years now, and I’m not closer to a cure than when I started out,” he said. “I’ve tried lots of things. In my defense, I’ve made more people better than worse.”

His approach to treating melasma is to begin with a KTP laser or a gentle IPL if discrete lesions or telangiectasia are present. Next, he applies hydroquinone followed by a series of treatment sessions with the Q-switched Nd:YAG laser or a conservative fractional laser. “This tends to induce remission, but is associated with a high rate of relapse,” he said.

Dr. Ross disclosed having research and financial ties to numerous pharmaceutical and device companies.

[email protected]