Lab mice

Photo by Aaron Logan

A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).

Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.

The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.

The researchers recounted these findings in Stem Cell Reports.

Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.

The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin^-Sca-1⁺c-Kit⁺ (LSK) cells, LSKCD150^-CD48^- cells, and LSKCD150⁺CD48^- cells—varied roughly 120-fold to 300-fold.

The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).

LSKCD150^-CD48^- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).

LSKCD150⁺CD48^- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).

Additional experiments showed that the frequency and function of LSKCD150^-CD48^- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150⁺CD48^- cells.

Mice lacking the Hopx gene had significantly lower numbers of LSKCD150^-CD48^- cells than wild-type mice, but LSK and LSKCD150⁺CD48^- counts were similar between Hopx^-/^- and wild-type mice.

The researchers also conducted competitive repopulation assays with HSCs from Hopx^-/^- and wild-type mice. HSCs from Hopx^-/^- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.

Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.

“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.

Lab mice

Photo by Aaron Logan

A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).

Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.

The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.

The researchers recounted these findings in Stem Cell Reports.

Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.

The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin^-Sca-1⁺c-Kit⁺ (LSK) cells, LSKCD150^-CD48^- cells, and LSKCD150⁺CD48^- cells—varied roughly 120-fold to 300-fold.

The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).

LSKCD150^-CD48^- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).

LSKCD150⁺CD48^- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).

Additional experiments showed that the frequency and function of LSKCD150^-CD48^- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150⁺CD48^- cells.

Mice lacking the Hopx gene had significantly lower numbers of LSKCD150^-CD48^- cells than wild-type mice, but LSK and LSKCD150⁺CD48^- counts were similar between Hopx^-/^- and wild-type mice.

The researchers also conducted competitive repopulation assays with HSCs from Hopx^-/^- and wild-type mice. HSCs from Hopx^-/^- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.

Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.

“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.

Lab mice

Photo by Aaron Logan

A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).

Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.

The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.

The researchers recounted these findings in Stem Cell Reports.

Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.

The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin^-Sca-1⁺c-Kit⁺ (LSK) cells, LSKCD150^-CD48^- cells, and LSKCD150⁺CD48^- cells—varied roughly 120-fold to 300-fold.

The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).

LSKCD150^-CD48^- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).

LSKCD150⁺CD48^- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).

Additional experiments showed that the frequency and function of LSKCD150^-CD48^- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150⁺CD48^- cells.

Mice lacking the Hopx gene had significantly lower numbers of LSKCD150^-CD48^- cells than wild-type mice, but LSK and LSKCD150⁺CD48^- counts were similar between Hopx^-/^- and wild-type mice.

The researchers also conducted competitive repopulation assays with HSCs from Hopx^-/^- and wild-type mice. HSCs from Hopx^-/^- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.

Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.

“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.

MIAMI BEACH – Patients with generalized anxiety disorder (GAD) saw significant improvement in their work, family, and social lives when taking vilazodone, compared with placebo.

However, vilazodone was associated with more side effects, and men taking vilazodone experienced more sexual side effects than those on placebo, according to Dr. David Sheehan, distinguished university health professor emeritus at the University of South Florida, Tampa.

Dr. Sheehan and his collaborators from Forest Laboratories presented their findings during a poster session at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and a partial 5-HT1a receptor agonist. Already approved for the treatment of major depressive disorder (MDD), vilazodone showed anxiolytic properties in post hoc analyses of the MDD clinical trial data.

The randomized, double-blind, placebo-controlled trial enrolled 404 otherwise healthy men and women who met DSM-IV criteria for GAD, exhibiting physical and psychiatric symptoms as well as functional impairment from the persistent and pervasive worry that characterize GAD. Individuals with clinically significant depression or any suicide risk, previous lack of response to adequate trials of other SSRIs, and those with serious medical conditions were excluded from the study.

Enrollees underwent a 1-week screening period, followed by 8 weeks of treatment, ending with a 1-week, double-blinded period of tapering off the study drug or placebo. Patients with insufficient improvement were allowed to increase vilazodone dosing from 20 mg to 40 mg at the end of the second or fourth study week, with no increases permitted after week four of the study.

Overall, total scores on the Hamilton Rating Scale for Anxiety (HAM-A) improved significantly more for those taking vilazodone than for those on placebo (total HAM-A score difference -2.2, P = 0.005). The psychic, somatic, and anxiety subscales also showed significant improvement, compared with placebo, as did the anxious and tension items.

The results indicate “greater improvement in anxiety symptoms associated with GAD,” said Dr. Sheehan and collaborators.

Scores on the Sheehan Disability Scale, used to assess social, family, and work/school functioning, improved significantly more for those on vilazodone than placebo, both for total score and for all domain subscores (total SDS score difference -1.89, P = 0.02).

Scores on two clinician rating tools, the Clinical Global Impression–Global Improvement (CGI-I) and the Clinical Global Impression–Severity (CGI-S) also improved significantly by least squares mean when vilazodone was compared with placebo (P = 0.003 and P = 0.0003, respectively).

Men taking vilazodone were more likely than those taking placebo to report sexual function-related adverse events, though overall numbers were low, and they also saw a small mean decrease on a sexual functioning questionnaire. These differences were not seen for women taking vilazodone, who reported a small improvement in sexual function, as did both men and women taking placebo.

There were no deaths and no serious abnormalities in laboratory values or ECGs in either group. Of the 404 evenly divided patients included in the safety analysis, significantly more patients discontinued vilazodone (58 patients, 28.7%) than discontinued placebo (39 patients, 19.3%, P < 0.05). Further, 22 patients (10.9%) stopped taking vilazodone because of adverse events, compared with 4 patients (2.0%) taking placebo (P < 0.05).

The most common treatment-emergent adverse event for the vilazodone group was nausea, occurring in 60 patients (29.7%), compared with 26 (12.9%) of the placebo group.

Forest Laboratories, an affiliate of Actavis, funded the study. Dr. Sheehan reported multiple financial affiliations with pharmaceutical companies, including Actavis and Forest Laboratories. All other authors are employees of Forest Research Institute.

koakes@frontlinemedcom.com

On Twitter @karioakes

MIAMI BEACH – Patients with generalized anxiety disorder (GAD) saw significant improvement in their work, family, and social lives when taking vilazodone, compared with placebo.

However, vilazodone was associated with more side effects, and men taking vilazodone experienced more sexual side effects than those on placebo, according to Dr. David Sheehan, distinguished university health professor emeritus at the University of South Florida, Tampa.

Dr. Sheehan and his collaborators from Forest Laboratories presented their findings during a poster session at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and a partial 5-HT1a receptor agonist. Already approved for the treatment of major depressive disorder (MDD), vilazodone showed anxiolytic properties in post hoc analyses of the MDD clinical trial data.

The randomized, double-blind, placebo-controlled trial enrolled 404 otherwise healthy men and women who met DSM-IV criteria for GAD, exhibiting physical and psychiatric symptoms as well as functional impairment from the persistent and pervasive worry that characterize GAD. Individuals with clinically significant depression or any suicide risk, previous lack of response to adequate trials of other SSRIs, and those with serious medical conditions were excluded from the study.

Enrollees underwent a 1-week screening period, followed by 8 weeks of treatment, ending with a 1-week, double-blinded period of tapering off the study drug or placebo. Patients with insufficient improvement were allowed to increase vilazodone dosing from 20 mg to 40 mg at the end of the second or fourth study week, with no increases permitted after week four of the study.

Overall, total scores on the Hamilton Rating Scale for Anxiety (HAM-A) improved significantly more for those taking vilazodone than for those on placebo (total HAM-A score difference -2.2, P = 0.005). The psychic, somatic, and anxiety subscales also showed significant improvement, compared with placebo, as did the anxious and tension items.

The results indicate “greater improvement in anxiety symptoms associated with GAD,” said Dr. Sheehan and collaborators.

Scores on the Sheehan Disability Scale, used to assess social, family, and work/school functioning, improved significantly more for those on vilazodone than placebo, both for total score and for all domain subscores (total SDS score difference -1.89, P = 0.02).

Scores on two clinician rating tools, the Clinical Global Impression–Global Improvement (CGI-I) and the Clinical Global Impression–Severity (CGI-S) also improved significantly by least squares mean when vilazodone was compared with placebo (P = 0.003 and P = 0.0003, respectively).

Men taking vilazodone were more likely than those taking placebo to report sexual function-related adverse events, though overall numbers were low, and they also saw a small mean decrease on a sexual functioning questionnaire. These differences were not seen for women taking vilazodone, who reported a small improvement in sexual function, as did both men and women taking placebo.

There were no deaths and no serious abnormalities in laboratory values or ECGs in either group. Of the 404 evenly divided patients included in the safety analysis, significantly more patients discontinued vilazodone (58 patients, 28.7%) than discontinued placebo (39 patients, 19.3%, P < 0.05). Further, 22 patients (10.9%) stopped taking vilazodone because of adverse events, compared with 4 patients (2.0%) taking placebo (P < 0.05).

The most common treatment-emergent adverse event for the vilazodone group was nausea, occurring in 60 patients (29.7%), compared with 26 (12.9%) of the placebo group.

Forest Laboratories, an affiliate of Actavis, funded the study. Dr. Sheehan reported multiple financial affiliations with pharmaceutical companies, including Actavis and Forest Laboratories. All other authors are employees of Forest Research Institute.

koakes@frontlinemedcom.com

On Twitter @karioakes

MIAMI BEACH – Patients with generalized anxiety disorder (GAD) saw significant improvement in their work, family, and social lives when taking vilazodone, compared with placebo.

However, vilazodone was associated with more side effects, and men taking vilazodone experienced more sexual side effects than those on placebo, according to Dr. David Sheehan, distinguished university health professor emeritus at the University of South Florida, Tampa.

Dr. Sheehan and his collaborators from Forest Laboratories presented their findings during a poster session at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and a partial 5-HT1a receptor agonist. Already approved for the treatment of major depressive disorder (MDD), vilazodone showed anxiolytic properties in post hoc analyses of the MDD clinical trial data.

The randomized, double-blind, placebo-controlled trial enrolled 404 otherwise healthy men and women who met DSM-IV criteria for GAD, exhibiting physical and psychiatric symptoms as well as functional impairment from the persistent and pervasive worry that characterize GAD. Individuals with clinically significant depression or any suicide risk, previous lack of response to adequate trials of other SSRIs, and those with serious medical conditions were excluded from the study.

Enrollees underwent a 1-week screening period, followed by 8 weeks of treatment, ending with a 1-week, double-blinded period of tapering off the study drug or placebo. Patients with insufficient improvement were allowed to increase vilazodone dosing from 20 mg to 40 mg at the end of the second or fourth study week, with no increases permitted after week four of the study.

Overall, total scores on the Hamilton Rating Scale for Anxiety (HAM-A) improved significantly more for those taking vilazodone than for those on placebo (total HAM-A score difference -2.2, P = 0.005). The psychic, somatic, and anxiety subscales also showed significant improvement, compared with placebo, as did the anxious and tension items.

The results indicate “greater improvement in anxiety symptoms associated with GAD,” said Dr. Sheehan and collaborators.

Scores on the Sheehan Disability Scale, used to assess social, family, and work/school functioning, improved significantly more for those on vilazodone than placebo, both for total score and for all domain subscores (total SDS score difference -1.89, P = 0.02).

Scores on two clinician rating tools, the Clinical Global Impression–Global Improvement (CGI-I) and the Clinical Global Impression–Severity (CGI-S) also improved significantly by least squares mean when vilazodone was compared with placebo (P = 0.003 and P = 0.0003, respectively).

Men taking vilazodone were more likely than those taking placebo to report sexual function-related adverse events, though overall numbers were low, and they also saw a small mean decrease on a sexual functioning questionnaire. These differences were not seen for women taking vilazodone, who reported a small improvement in sexual function, as did both men and women taking placebo.

There were no deaths and no serious abnormalities in laboratory values or ECGs in either group. Of the 404 evenly divided patients included in the safety analysis, significantly more patients discontinued vilazodone (58 patients, 28.7%) than discontinued placebo (39 patients, 19.3%, P < 0.05). Further, 22 patients (10.9%) stopped taking vilazodone because of adverse events, compared with 4 patients (2.0%) taking placebo (P < 0.05).

The most common treatment-emergent adverse event for the vilazodone group was nausea, occurring in 60 patients (29.7%), compared with 26 (12.9%) of the placebo group.

Forest Laboratories, an affiliate of Actavis, funded the study. Dr. Sheehan reported multiple financial affiliations with pharmaceutical companies, including Actavis and Forest Laboratories. All other authors are employees of Forest Research Institute.

koakes@frontlinemedcom.com

On Twitter @karioakes

Micrograph showing WM

The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).

The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.

Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.

Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

Micrograph showing WM

The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).

The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.

Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.

Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

Micrograph showing WM

The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).

The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.

Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.

Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

TORONTO – Forgoing bridging anticoagulation in patients with atrial fibrillation (AF) is noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreases the risk of major bleeding.

Those results emerged from trial data presented at the International Society on Thrombosis and Haemostasis congress and published simultaneously in the New England Journal of Medicine. Study investigator Dr. Thomas Ortel, chief of the division of hematology at Duke University Medical Center, Durham, N.C., discussed results of the BRIDGE (Effectiveness of Bridging Anticoagulation for Surgery) trial, which evaluated the safety and efficacy of bridging anticoagulant therapy.

Courtesy International Society on Thrombosis and Haemostasis

Bridging anticoagulation is frequently used in patients taking chronic oral anticoagulant therapy who need their anticoagulation transiently held for an operation or invasive procedure. The need for bridging anticoagulation never has been shown definitively, however, Dr. Ortel said in an interview.

“This is the first prospective, randomized, placebo-controlled, double-blind clinical trial to investigate the role of bridging anticoagulant therapy in patients with AF on chronic anticoagulation with warfarin who need the anticoagulant therapy held for an elective operation or invasive procedure,” he said.

Dr. Ortel and his coauthors evaluated 1,884 patients in the trial, which compared bridging and no bridging in patients with nonvalvular/valvular AF or atrial flutter who required warfarin interruption for elective surgery. The median age was 72.7 years, and 73% of patients were male. A total of 336 patients had a history of stroke or transient ischemic attack.

After stopping warfarin 5 days before the procedure, study participants received dalteparin 100 IU/kg (934 patients) or matching placebo (950 patients) for 3 days before and 5-9 days after the procedure. Dalteparin/placebo was resumed 12-24 hours after minor surgery and 48-72 hours after major surgery.

Warfarin was resumed 24 hours or less after the procedure. Follow-up lasted 30 ± 7 days after the procedure. Primary outcomes were arterial thromboembolism and major bleeding. Secondary outcomes were minor bleeding, death, myocardial infarction, and venous thromboembolism.

Protocol adherence occurred in 81% of patients before the procedure, and in 94.5% of patients post procedure.

The incidence of arterial thromboembolism was 0.4% in the no-bridging group, compared with 0.3% in the bridging group (95% confidence interval, –0.6 to 0.8; P = .01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20-0.78; P = .005 for superiority).

“Current practice guidelines provide weak and inconsistent recommendations concerning the need for bridging anticoagulation,” Dr. Ortel said. “This study provides the highest level of evidence to support a strong recommendation concerning the role of bridging in this patient population.”

It is estimated that approximately one in six warfarin-treated patients with AF will need anticoagulation transiently held for an elective operation or invasive procedure each year, making this a common clinical scenario for providers, Dr. Ortel said. Knowing the findings from the BRIDGE trial will help guide clinicians in making decisions when this situation arises in their patients, he concluded.

“With the introduction of the direct oral anticoagulants, we will now need to develop periprocedural approaches to manage patients on a variety of different agents,” he said. “Warfarin continues to be extensively used in many of these patients, however, and the BRIDGE trial will contribute to improved management for these individuals.”

In response to an audience member’s question about which patients should receive bridging anticoagulation, Dr. Ortel said that “right now, our data would suggest that for AF patients, we don’t need to bridge.”

“I can’t say that, necessarily, for prosthetic heart valves or for venous thromboembolism. I think some of the recommendations that you’ve seen in the guidelines where people try to stratify this by how recently they had thromboembolism or by what type of heart valve they have – those might be the higher-risk patients to consider. But that’s all based on existing guidelines and no prospective data, so I feel comfortable telling you who you don’t need to bridge in, but I’m not going to tell you who you should,” he added.

The BRIDGE Trial was sponsored by the National Heart, Lung, and Blood Institute. Dr. Ortel disclosed grant/research support from Eisai Co. Ltd and Pfizer Inc.

sworcester@frontlinemedcom.com

TORONTO – Forgoing bridging anticoagulation in patients with atrial fibrillation (AF) is noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreases the risk of major bleeding.

Those results emerged from trial data presented at the International Society on Thrombosis and Haemostasis congress and published simultaneously in the New England Journal of Medicine. Study investigator Dr. Thomas Ortel, chief of the division of hematology at Duke University Medical Center, Durham, N.C., discussed results of the BRIDGE (Effectiveness of Bridging Anticoagulation for Surgery) trial, which evaluated the safety and efficacy of bridging anticoagulant therapy.

Courtesy International Society on Thrombosis and Haemostasis

Bridging anticoagulation is frequently used in patients taking chronic oral anticoagulant therapy who need their anticoagulation transiently held for an operation or invasive procedure. The need for bridging anticoagulation never has been shown definitively, however, Dr. Ortel said in an interview.

“This is the first prospective, randomized, placebo-controlled, double-blind clinical trial to investigate the role of bridging anticoagulant therapy in patients with AF on chronic anticoagulation with warfarin who need the anticoagulant therapy held for an elective operation or invasive procedure,” he said.

Dr. Ortel and his coauthors evaluated 1,884 patients in the trial, which compared bridging and no bridging in patients with nonvalvular/valvular AF or atrial flutter who required warfarin interruption for elective surgery. The median age was 72.7 years, and 73% of patients were male. A total of 336 patients had a history of stroke or transient ischemic attack.

After stopping warfarin 5 days before the procedure, study participants received dalteparin 100 IU/kg (934 patients) or matching placebo (950 patients) for 3 days before and 5-9 days after the procedure. Dalteparin/placebo was resumed 12-24 hours after minor surgery and 48-72 hours after major surgery.

Warfarin was resumed 24 hours or less after the procedure. Follow-up lasted 30 ± 7 days after the procedure. Primary outcomes were arterial thromboembolism and major bleeding. Secondary outcomes were minor bleeding, death, myocardial infarction, and venous thromboembolism.

Protocol adherence occurred in 81% of patients before the procedure, and in 94.5% of patients post procedure.

The incidence of arterial thromboembolism was 0.4% in the no-bridging group, compared with 0.3% in the bridging group (95% confidence interval, –0.6 to 0.8; P = .01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20-0.78; P = .005 for superiority).

“Current practice guidelines provide weak and inconsistent recommendations concerning the need for bridging anticoagulation,” Dr. Ortel said. “This study provides the highest level of evidence to support a strong recommendation concerning the role of bridging in this patient population.”

It is estimated that approximately one in six warfarin-treated patients with AF will need anticoagulation transiently held for an elective operation or invasive procedure each year, making this a common clinical scenario for providers, Dr. Ortel said. Knowing the findings from the BRIDGE trial will help guide clinicians in making decisions when this situation arises in their patients, he concluded.

“With the introduction of the direct oral anticoagulants, we will now need to develop periprocedural approaches to manage patients on a variety of different agents,” he said. “Warfarin continues to be extensively used in many of these patients, however, and the BRIDGE trial will contribute to improved management for these individuals.”

In response to an audience member’s question about which patients should receive bridging anticoagulation, Dr. Ortel said that “right now, our data would suggest that for AF patients, we don’t need to bridge.”

“I can’t say that, necessarily, for prosthetic heart valves or for venous thromboembolism. I think some of the recommendations that you’ve seen in the guidelines where people try to stratify this by how recently they had thromboembolism or by what type of heart valve they have – those might be the higher-risk patients to consider. But that’s all based on existing guidelines and no prospective data, so I feel comfortable telling you who you don’t need to bridge in, but I’m not going to tell you who you should,” he added.

The BRIDGE Trial was sponsored by the National Heart, Lung, and Blood Institute. Dr. Ortel disclosed grant/research support from Eisai Co. Ltd and Pfizer Inc.

sworcester@frontlinemedcom.com

TORONTO – Forgoing bridging anticoagulation in patients with atrial fibrillation (AF) is noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreases the risk of major bleeding.

Those results emerged from trial data presented at the International Society on Thrombosis and Haemostasis congress and published simultaneously in the New England Journal of Medicine. Study investigator Dr. Thomas Ortel, chief of the division of hematology at Duke University Medical Center, Durham, N.C., discussed results of the BRIDGE (Effectiveness of Bridging Anticoagulation for Surgery) trial, which evaluated the safety and efficacy of bridging anticoagulant therapy.

Courtesy International Society on Thrombosis and Haemostasis

Bridging anticoagulation is frequently used in patients taking chronic oral anticoagulant therapy who need their anticoagulation transiently held for an operation or invasive procedure. The need for bridging anticoagulation never has been shown definitively, however, Dr. Ortel said in an interview.

“This is the first prospective, randomized, placebo-controlled, double-blind clinical trial to investigate the role of bridging anticoagulant therapy in patients with AF on chronic anticoagulation with warfarin who need the anticoagulant therapy held for an elective operation or invasive procedure,” he said.

Dr. Ortel and his coauthors evaluated 1,884 patients in the trial, which compared bridging and no bridging in patients with nonvalvular/valvular AF or atrial flutter who required warfarin interruption for elective surgery. The median age was 72.7 years, and 73% of patients were male. A total of 336 patients had a history of stroke or transient ischemic attack.

After stopping warfarin 5 days before the procedure, study participants received dalteparin 100 IU/kg (934 patients) or matching placebo (950 patients) for 3 days before and 5-9 days after the procedure. Dalteparin/placebo was resumed 12-24 hours after minor surgery and 48-72 hours after major surgery.

Warfarin was resumed 24 hours or less after the procedure. Follow-up lasted 30 ± 7 days after the procedure. Primary outcomes were arterial thromboembolism and major bleeding. Secondary outcomes were minor bleeding, death, myocardial infarction, and venous thromboembolism.

Protocol adherence occurred in 81% of patients before the procedure, and in 94.5% of patients post procedure.

The incidence of arterial thromboembolism was 0.4% in the no-bridging group, compared with 0.3% in the bridging group (95% confidence interval, –0.6 to 0.8; P = .01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20-0.78; P = .005 for superiority).

“Current practice guidelines provide weak and inconsistent recommendations concerning the need for bridging anticoagulation,” Dr. Ortel said. “This study provides the highest level of evidence to support a strong recommendation concerning the role of bridging in this patient population.”

It is estimated that approximately one in six warfarin-treated patients with AF will need anticoagulation transiently held for an elective operation or invasive procedure each year, making this a common clinical scenario for providers, Dr. Ortel said. Knowing the findings from the BRIDGE trial will help guide clinicians in making decisions when this situation arises in their patients, he concluded.

“With the introduction of the direct oral anticoagulants, we will now need to develop periprocedural approaches to manage patients on a variety of different agents,” he said. “Warfarin continues to be extensively used in many of these patients, however, and the BRIDGE trial will contribute to improved management for these individuals.”

In response to an audience member’s question about which patients should receive bridging anticoagulation, Dr. Ortel said that “right now, our data would suggest that for AF patients, we don’t need to bridge.”

“I can’t say that, necessarily, for prosthetic heart valves or for venous thromboembolism. I think some of the recommendations that you’ve seen in the guidelines where people try to stratify this by how recently they had thromboembolism or by what type of heart valve they have – those might be the higher-risk patients to consider. But that’s all based on existing guidelines and no prospective data, so I feel comfortable telling you who you don’t need to bridge in, but I’m not going to tell you who you should,” he added.

The BRIDGE Trial was sponsored by the National Heart, Lung, and Blood Institute. Dr. Ortel disclosed grant/research support from Eisai Co. Ltd and Pfizer Inc.

sworcester@frontlinemedcom.com

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

VANCOUVER – Dapsone gel 5% proved effective and well tolerated for facial acne in women with skin of color in a multicenter pilot study.

The study was conducted because even though dapsone gel 5% (Aczone) is approved for the treatment of acne on the strength of two pivotal randomized, double-blind clinical trials totaling more than 3,000 patients, scant data exist on the topical agent’s performance in women with skin of color, Dr. Andrew F. Alexis explained at the World Congress of Dermatology.

He presented an open-label, seven-center, 12-week, single-arm study involving 68 women of color – three-quarters of whom were black – who treated their facial acne with dapsone gel 5% twice daily as monotherapy.

Participants averaged a mean baseline score of 2.6 on the 0-4 Global Acne Assessment Score (GAAS), with a mean total of 50 inflammatory and noninflammatory acne lesions on the face.

The primary endpoint was change in GAAS at 12 weeks, although patients also were formally assessed at 2 and 6 weeks. The average reduction in GAAS was 8.8% at 2 weeks, 20% at 6 weeks, and 39% at 12 weeks. At week 12, 43% of the women were categorized as responders, meaning they had a GAAS of 0 (meaning no acne lesions) or 1 (indicating mild disease), reported Dr. Alexis of Mt. Sinai Hospital in New York.

Total lesion counts dropped steadily throughout the 12-week trial: by 16% from baseline to week 2, 30% at week 6, and 52% at week 12. Inflammatory lesions responded best, with a 65% reduction in number at week 12.

Patient-reported outcomes on the validated, 17-item Acne Symptom and Impact Scale were favorable: Reductions of roughly 50% were documented over 12 weeks on the scale’s two domains, acne signs and quality of life impact.

No clinically meaningful treatment-related adverse events were reported in the study, although a handful of women reported trace levels of redness, burning, dryness, and/or oiliness.

Acne is more common among African American than white women. In a large epidemiologic study of adolescent and adult women, the prevalence of acne vulgaris was 37% in African Americans, compared with 24% in whites (J. Eur. Acad. Dermatol. Venereol. 2011;25:1054-60).

Dr. Alexis’ study was sponsored by Allergan. He reported serving as a consultant to and receiving research grants from the company.

bjancin@frontlinemedcom

VANCOUVER – Dapsone gel 5% proved effective and well tolerated for facial acne in women with skin of color in a multicenter pilot study.

The study was conducted because even though dapsone gel 5% (Aczone) is approved for the treatment of acne on the strength of two pivotal randomized, double-blind clinical trials totaling more than 3,000 patients, scant data exist on the topical agent’s performance in women with skin of color, Dr. Andrew F. Alexis explained at the World Congress of Dermatology.

He presented an open-label, seven-center, 12-week, single-arm study involving 68 women of color – three-quarters of whom were black – who treated their facial acne with dapsone gel 5% twice daily as monotherapy.

Participants averaged a mean baseline score of 2.6 on the 0-4 Global Acne Assessment Score (GAAS), with a mean total of 50 inflammatory and noninflammatory acne lesions on the face.

The primary endpoint was change in GAAS at 12 weeks, although patients also were formally assessed at 2 and 6 weeks. The average reduction in GAAS was 8.8% at 2 weeks, 20% at 6 weeks, and 39% at 12 weeks. At week 12, 43% of the women were categorized as responders, meaning they had a GAAS of 0 (meaning no acne lesions) or 1 (indicating mild disease), reported Dr. Alexis of Mt. Sinai Hospital in New York.

Total lesion counts dropped steadily throughout the 12-week trial: by 16% from baseline to week 2, 30% at week 6, and 52% at week 12. Inflammatory lesions responded best, with a 65% reduction in number at week 12.

Patient-reported outcomes on the validated, 17-item Acne Symptom and Impact Scale were favorable: Reductions of roughly 50% were documented over 12 weeks on the scale’s two domains, acne signs and quality of life impact.

No clinically meaningful treatment-related adverse events were reported in the study, although a handful of women reported trace levels of redness, burning, dryness, and/or oiliness.

Acne is more common among African American than white women. In a large epidemiologic study of adolescent and adult women, the prevalence of acne vulgaris was 37% in African Americans, compared with 24% in whites (J. Eur. Acad. Dermatol. Venereol. 2011;25:1054-60).

Dr. Alexis’ study was sponsored by Allergan. He reported serving as a consultant to and receiving research grants from the company.

bjancin@frontlinemedcom

VANCOUVER – Dapsone gel 5% proved effective and well tolerated for facial acne in women with skin of color in a multicenter pilot study.

The study was conducted because even though dapsone gel 5% (Aczone) is approved for the treatment of acne on the strength of two pivotal randomized, double-blind clinical trials totaling more than 3,000 patients, scant data exist on the topical agent’s performance in women with skin of color, Dr. Andrew F. Alexis explained at the World Congress of Dermatology.

He presented an open-label, seven-center, 12-week, single-arm study involving 68 women of color – three-quarters of whom were black – who treated their facial acne with dapsone gel 5% twice daily as monotherapy.

Participants averaged a mean baseline score of 2.6 on the 0-4 Global Acne Assessment Score (GAAS), with a mean total of 50 inflammatory and noninflammatory acne lesions on the face.

The primary endpoint was change in GAAS at 12 weeks, although patients also were formally assessed at 2 and 6 weeks. The average reduction in GAAS was 8.8% at 2 weeks, 20% at 6 weeks, and 39% at 12 weeks. At week 12, 43% of the women were categorized as responders, meaning they had a GAAS of 0 (meaning no acne lesions) or 1 (indicating mild disease), reported Dr. Alexis of Mt. Sinai Hospital in New York.

Total lesion counts dropped steadily throughout the 12-week trial: by 16% from baseline to week 2, 30% at week 6, and 52% at week 12. Inflammatory lesions responded best, with a 65% reduction in number at week 12.

Patient-reported outcomes on the validated, 17-item Acne Symptom and Impact Scale were favorable: Reductions of roughly 50% were documented over 12 weeks on the scale’s two domains, acne signs and quality of life impact.

No clinically meaningful treatment-related adverse events were reported in the study, although a handful of women reported trace levels of redness, burning, dryness, and/or oiliness.

Acne is more common among African American than white women. In a large epidemiologic study of adolescent and adult women, the prevalence of acne vulgaris was 37% in African Americans, compared with 24% in whites (J. Eur. Acad. Dermatol. Venereol. 2011;25:1054-60).

Dr. Alexis’ study was sponsored by Allergan. He reported serving as a consultant to and receiving research grants from the company.

bjancin@frontlinemedcom

My late father, H. H. Samson, an anesthesiologist, was convinced that hyperuricemia and over consumption of sugar were instigating factors for vascular disease and published on the subject (S. Afr. Med. J. 1978 Oct 7;54:590-1.) It has only taken some 30-odd years to prove him right! - Dr. Russell Samson, medical editor, Vascular Specialist.

Gout’s association with a host of vascular events was confirmed in a new study that explored the links between the inflammatory condition and coronary artery disease, peripheral vascular disease, and cerebrovascular events.

Though both men and women with gout were at increased risk for vascular events overall, the association appeared strongest for women. Dr. Lorna Clarson of Keele (England) University and her associates drew these conclusions from a retrospective cohort study of men and women with an incident diagnosis of gout (Ann. Rheum. Dis. 2015;74:642-7).

Gout, caused by the deposition of uric acid crystals in joints, is characterized by acute flares of intensely painful and inflamed joints. However, the state of hyperuricemia that predisposes patients to acute attacks of gout may precede the first attack by years, and may persist between flares. The proinflammatory course of the natural history of gout has increasingly been recognized as a potential contributor to vascular disease.

The precise mechanism by which gout may increase vascular risk has not been identified. Dr. Clarson and associates noted that in addition to the acute and chronic inflammation associated with gout and hyperuricemia, serum uric acid may have a more direct effect on vascular health, as urate crystal deposition on vessel walls may promote vascular damage.

To clarify gout’s impact on vascular risk, Dr. Clarson and her associates used the Clinical Practice Datalink, a large United Kingdom health database, to compare 8,366 patients with gout to 39,766 age- and sex-matched controls. None of those studied had a baseline history of vascular disease, and all were aged 50 or older.

Careful accounting for covariates was accomplished by multivariate analysis that took into account sex, age, body mass index, tobacco and alcohol consumption, statin or aspirin use, and any history of hypertension, dyslipidemia, or chronic kidney disease. In addition, the study employed the composite Charlson Comorbidity Index, which weights 19 comorbid conditions – including diabetes – to arrive at a single score that captures many risk factors. Patients in the cohort were tracked until their first vascular event, or until death or loss to follow-up.

To assess the incidence of vascular events, the study noted the first recording in the medical record of any events signaling vascular disease. These included angina or myocardial infarction, transient ischemic attack and stroke, and a range of diagnoses associated with peripheral vascular disease.

Final analysis after accounting for the many covariates tracked in the study showed increased risk for vascular events for those with gout, with a definite difference between the sexes. For men, gout predicted an increased risk of any vascular event (hazard ratio, 1.06; 95% confidence interval, 1.01–1.12) and of coronary heart disease and peripheral vascular disease.

For women, gout predicted an increased risk of all vascular events (HR, 1.25; 95% CI, 1.15-1.35) except myocardial infarction and cerebrovascular disease overall. Further, the degree of increased risk of vascular events was greater for women than for men with gout (P < .001 for intersex difference).

Noting that “clinical management of gout in primary care is suboptimal,” Dr. Clarson and her colleagues urged greater attention to screening for vascular risk in those diagnosed with gout; these individuals comprise a significant population of over 8 million people in the United States. Regarding the sex differences unearthed in their study,

Dr. Clarson and her associates observed that “both gout and vascular disease have historically been considered diseases of men ... [M]ore attention should be paid to prompt and reliable diagnosis of gout, followed by optimal management in female patients, including serious consideration of vascular risk reduction.”

In an editorial accompanying Dr. Clarson’s report (Ann. Rheum. Dis. 2015;74:631-4),Dr. Jasvinder Singh, commented that Dr. Clarson and colleagues’ study is limited by its lack of validation of gout and cardiac diagnoses and the self-selection bias inherent in using primary care registries, rather than a true population-based cohort.

Patients older than 35 or 40 with gout should be screened and followed with lipid profiles, hemoglobin A_1c levels, blood pressure levels, and smoking status, and should undergo an assessment of other lifestyle factors that may impact cardiovascular risk, added Dr Singh, who a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham.

Recognizing gout’s contribution to cardiac risk, and managing both the disease and the associated risk factors, will be a key task for primary care doctors, rheumatologists, and cardiologists going forward, Dr. Singh concluded.

The United Kingdom’s National School for Primary Research funded the study. The authors reported no relevant disclosures. Dr. Singh reported receiving research and travel grants from Takeda and Savient, and consultant fees from Takeda, Savient, Regeneron, and Allergan.

My late father, H. H. Samson, an anesthesiologist, was convinced that hyperuricemia and over consumption of sugar were instigating factors for vascular disease and published on the subject (S. Afr. Med. J. 1978 Oct 7;54:590-1.) It has only taken some 30-odd years to prove him right! - Dr. Russell Samson, medical editor, Vascular Specialist.

Gout’s association with a host of vascular events was confirmed in a new study that explored the links between the inflammatory condition and coronary artery disease, peripheral vascular disease, and cerebrovascular events.

Though both men and women with gout were at increased risk for vascular events overall, the association appeared strongest for women. Dr. Lorna Clarson of Keele (England) University and her associates drew these conclusions from a retrospective cohort study of men and women with an incident diagnosis of gout (Ann. Rheum. Dis. 2015;74:642-7).

Gout, caused by the deposition of uric acid crystals in joints, is characterized by acute flares of intensely painful and inflamed joints. However, the state of hyperuricemia that predisposes patients to acute attacks of gout may precede the first attack by years, and may persist between flares. The proinflammatory course of the natural history of gout has increasingly been recognized as a potential contributor to vascular disease.

The precise mechanism by which gout may increase vascular risk has not been identified. Dr. Clarson and associates noted that in addition to the acute and chronic inflammation associated with gout and hyperuricemia, serum uric acid may have a more direct effect on vascular health, as urate crystal deposition on vessel walls may promote vascular damage.

To clarify gout’s impact on vascular risk, Dr. Clarson and her associates used the Clinical Practice Datalink, a large United Kingdom health database, to compare 8,366 patients with gout to 39,766 age- and sex-matched controls. None of those studied had a baseline history of vascular disease, and all were aged 50 or older.

Careful accounting for covariates was accomplished by multivariate analysis that took into account sex, age, body mass index, tobacco and alcohol consumption, statin or aspirin use, and any history of hypertension, dyslipidemia, or chronic kidney disease. In addition, the study employed the composite Charlson Comorbidity Index, which weights 19 comorbid conditions – including diabetes – to arrive at a single score that captures many risk factors. Patients in the cohort were tracked until their first vascular event, or until death or loss to follow-up.

To assess the incidence of vascular events, the study noted the first recording in the medical record of any events signaling vascular disease. These included angina or myocardial infarction, transient ischemic attack and stroke, and a range of diagnoses associated with peripheral vascular disease.

Final analysis after accounting for the many covariates tracked in the study showed increased risk for vascular events for those with gout, with a definite difference between the sexes. For men, gout predicted an increased risk of any vascular event (hazard ratio, 1.06; 95% confidence interval, 1.01–1.12) and of coronary heart disease and peripheral vascular disease.

For women, gout predicted an increased risk of all vascular events (HR, 1.25; 95% CI, 1.15-1.35) except myocardial infarction and cerebrovascular disease overall. Further, the degree of increased risk of vascular events was greater for women than for men with gout (P < .001 for intersex difference).

Noting that “clinical management of gout in primary care is suboptimal,” Dr. Clarson and her colleagues urged greater attention to screening for vascular risk in those diagnosed with gout; these individuals comprise a significant population of over 8 million people in the United States. Regarding the sex differences unearthed in their study,

Dr. Clarson and her associates observed that “both gout and vascular disease have historically been considered diseases of men ... [M]ore attention should be paid to prompt and reliable diagnosis of gout, followed by optimal management in female patients, including serious consideration of vascular risk reduction.”

In an editorial accompanying Dr. Clarson’s report (Ann. Rheum. Dis. 2015;74:631-4),Dr. Jasvinder Singh, commented that Dr. Clarson and colleagues’ study is limited by its lack of validation of gout and cardiac diagnoses and the self-selection bias inherent in using primary care registries, rather than a true population-based cohort.

Patients older than 35 or 40 with gout should be screened and followed with lipid profiles, hemoglobin A_1c levels, blood pressure levels, and smoking status, and should undergo an assessment of other lifestyle factors that may impact cardiovascular risk, added Dr Singh, who a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham.

Recognizing gout’s contribution to cardiac risk, and managing both the disease and the associated risk factors, will be a key task for primary care doctors, rheumatologists, and cardiologists going forward, Dr. Singh concluded.

The United Kingdom’s National School for Primary Research funded the study. The authors reported no relevant disclosures. Dr. Singh reported receiving research and travel grants from Takeda and Savient, and consultant fees from Takeda, Savient, Regeneron, and Allergan.

My late father, H. H. Samson, an anesthesiologist, was convinced that hyperuricemia and over consumption of sugar were instigating factors for vascular disease and published on the subject (S. Afr. Med. J. 1978 Oct 7;54:590-1.) It has only taken some 30-odd years to prove him right! - Dr. Russell Samson, medical editor, Vascular Specialist.

Gout’s association with a host of vascular events was confirmed in a new study that explored the links between the inflammatory condition and coronary artery disease, peripheral vascular disease, and cerebrovascular events.

Though both men and women with gout were at increased risk for vascular events overall, the association appeared strongest for women. Dr. Lorna Clarson of Keele (England) University and her associates drew these conclusions from a retrospective cohort study of men and women with an incident diagnosis of gout (Ann. Rheum. Dis. 2015;74:642-7).

Gout, caused by the deposition of uric acid crystals in joints, is characterized by acute flares of intensely painful and inflamed joints. However, the state of hyperuricemia that predisposes patients to acute attacks of gout may precede the first attack by years, and may persist between flares. The proinflammatory course of the natural history of gout has increasingly been recognized as a potential contributor to vascular disease.

The precise mechanism by which gout may increase vascular risk has not been identified. Dr. Clarson and associates noted that in addition to the acute and chronic inflammation associated with gout and hyperuricemia, serum uric acid may have a more direct effect on vascular health, as urate crystal deposition on vessel walls may promote vascular damage.

To clarify gout’s impact on vascular risk, Dr. Clarson and her associates used the Clinical Practice Datalink, a large United Kingdom health database, to compare 8,366 patients with gout to 39,766 age- and sex-matched controls. None of those studied had a baseline history of vascular disease, and all were aged 50 or older.

Careful accounting for covariates was accomplished by multivariate analysis that took into account sex, age, body mass index, tobacco and alcohol consumption, statin or aspirin use, and any history of hypertension, dyslipidemia, or chronic kidney disease. In addition, the study employed the composite Charlson Comorbidity Index, which weights 19 comorbid conditions – including diabetes – to arrive at a single score that captures many risk factors. Patients in the cohort were tracked until their first vascular event, or until death or loss to follow-up.

To assess the incidence of vascular events, the study noted the first recording in the medical record of any events signaling vascular disease. These included angina or myocardial infarction, transient ischemic attack and stroke, and a range of diagnoses associated with peripheral vascular disease.

Final analysis after accounting for the many covariates tracked in the study showed increased risk for vascular events for those with gout, with a definite difference between the sexes. For men, gout predicted an increased risk of any vascular event (hazard ratio, 1.06; 95% confidence interval, 1.01–1.12) and of coronary heart disease and peripheral vascular disease.

For women, gout predicted an increased risk of all vascular events (HR, 1.25; 95% CI, 1.15-1.35) except myocardial infarction and cerebrovascular disease overall. Further, the degree of increased risk of vascular events was greater for women than for men with gout (P < .001 for intersex difference).

Noting that “clinical management of gout in primary care is suboptimal,” Dr. Clarson and her colleagues urged greater attention to screening for vascular risk in those diagnosed with gout; these individuals comprise a significant population of over 8 million people in the United States. Regarding the sex differences unearthed in their study,

Dr. Clarson and her associates observed that “both gout and vascular disease have historically been considered diseases of men ... [M]ore attention should be paid to prompt and reliable diagnosis of gout, followed by optimal management in female patients, including serious consideration of vascular risk reduction.”

In an editorial accompanying Dr. Clarson’s report (Ann. Rheum. Dis. 2015;74:631-4),Dr. Jasvinder Singh, commented that Dr. Clarson and colleagues’ study is limited by its lack of validation of gout and cardiac diagnoses and the self-selection bias inherent in using primary care registries, rather than a true population-based cohort.

Patients older than 35 or 40 with gout should be screened and followed with lipid profiles, hemoglobin A_1c levels, blood pressure levels, and smoking status, and should undergo an assessment of other lifestyle factors that may impact cardiovascular risk, added Dr Singh, who a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham.

Recognizing gout’s contribution to cardiac risk, and managing both the disease and the associated risk factors, will be a key task for primary care doctors, rheumatologists, and cardiologists going forward, Dr. Singh concluded.

The United Kingdom’s National School for Primary Research funded the study. The authors reported no relevant disclosures. Dr. Singh reported receiving research and travel grants from Takeda and Savient, and consultant fees from Takeda, Savient, Regeneron, and Allergan.

Osteoblasts (purple) on the

rim of a bone spicule (pink)

New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.

Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.

“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.

“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”

Dr Yang and her colleagues explained this phenomenon in Blood.

The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.

The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.

Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.

Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.

Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.

In their final experiments, the investigators looked at Runx2 expression in human samples.

The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.

The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.

“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.

She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.

Osteoblasts (purple) on the

rim of a bone spicule (pink)

New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.

Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.

“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.

“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”

Dr Yang and her colleagues explained this phenomenon in Blood.

The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.

The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.

Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.

Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.

Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.

In their final experiments, the investigators looked at Runx2 expression in human samples.

The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.

The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.

“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.

She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.

Osteoblasts (purple) on the

rim of a bone spicule (pink)

New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.

Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.

“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.

“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”

Dr Yang and her colleagues explained this phenomenon in Blood.

The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.

The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.

Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.

Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.

Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.

In their final experiments, the investigators looked at Runx2 expression in human samples.

The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.

The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.

“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.

She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.

Doctor and cancer patient

Photo courtesy of NCI

and Mathews Media Group

Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.

Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.

There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.

“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.

Dr Narang and his colleagues described this research in JAMA Oncology.

The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.

The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.

The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).

“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.

Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).

The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).

On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).

The researchers said they observed the same trends regardless of who completed the exit survey.

Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.

“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”

Doctor and cancer patient

Photo courtesy of NCI

and Mathews Media Group

Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.

Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.

There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.

“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.

Dr Narang and his colleagues described this research in JAMA Oncology.

The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.

The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.

The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).

“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.

Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).

The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).

On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).

The researchers said they observed the same trends regardless of who completed the exit survey.

Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.

“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”

Doctor and cancer patient

Photo courtesy of NCI

and Mathews Media Group

Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.

Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.

There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.

“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.

Dr Narang and his colleagues described this research in JAMA Oncology.

The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.

The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.

The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).

“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.

Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).

The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).

On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).

The researchers said they observed the same trends regardless of who completed the exit survey.

Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.

“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”

 

 

NK cell destroying a cancer cell

Image by Joshua Strokes

 

Researchers say they have determined how lymphoma cells evade natural killer (NK) cells, and this discovery has revealed potential solutions to the problem.

The team found that NK-cell activation and a second, “triggering” event are both necessary for NK cells to exhibit cytotoxicity in the presence of B-cell lymphoma.

Previous research demonstrated this 2-step process in vitro. Now, researchers have shown that it occurs in vivo.

Dr Ralph Mocikat, of Helmholtz Zentrum München in Munich, Germany, and his colleagues described this research in the European Journal of Immunology.

The team conducted experiments using transplantable tumors, a λ-myc-transgenic model of endogenously arising lymphoma that mimics human Burkitt lymphoma, and mice deficient in the NK group 2 D (NKG2D) receptor.

The experiments showed that NK cells could eliminate lymphoma cells after receiving 2 signals. The first was NK-cell activation, which gave rise to IFN-γ expression.

The researchers found that NK cells could be activated in the presence of MHC class I_low tumor cells or by injecting bone marrow-derived dendritic cells. Previous research had shown that interleukin 2 (IL-2) and IL-15 could activate NK cells.

The second step involved the NKG2D receptor and its ligands. NKG2D ligands are located on the surface of tumor cells and bind to NK cells. The researchers found that, if these ligands are down-regulated, the NK cells cannot carry out cytotoxic activity.

However, the team found they could increase NKG2D ligand levels. They introduced bortezomib to the tumor cell line 291 and saw a roughly 4-fold increase in NKG2D ligand levels.

“Our results show that the transfer of NK cells is a possible strategic option to treat B-cell lymphoma,” Dr Mocikat said. “According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity.”

 

 

NK cell destroying a cancer cell

Image by Joshua Strokes

 

Researchers say they have determined how lymphoma cells evade natural killer (NK) cells, and this discovery has revealed potential solutions to the problem.

The team found that NK-cell activation and a second, “triggering” event are both necessary for NK cells to exhibit cytotoxicity in the presence of B-cell lymphoma.

Previous research demonstrated this 2-step process in vitro. Now, researchers have shown that it occurs in vivo.

Dr Ralph Mocikat, of Helmholtz Zentrum München in Munich, Germany, and his colleagues described this research in the European Journal of Immunology.

The team conducted experiments using transplantable tumors, a λ-myc-transgenic model of endogenously arising lymphoma that mimics human Burkitt lymphoma, and mice deficient in the NK group 2 D (NKG2D) receptor.

The experiments showed that NK cells could eliminate lymphoma cells after receiving 2 signals. The first was NK-cell activation, which gave rise to IFN-γ expression.

The researchers found that NK cells could be activated in the presence of MHC class I_low tumor cells or by injecting bone marrow-derived dendritic cells. Previous research had shown that interleukin 2 (IL-2) and IL-15 could activate NK cells.

The second step involved the NKG2D receptor and its ligands. NKG2D ligands are located on the surface of tumor cells and bind to NK cells. The researchers found that, if these ligands are down-regulated, the NK cells cannot carry out cytotoxic activity.

However, the team found they could increase NKG2D ligand levels. They introduced bortezomib to the tumor cell line 291 and saw a roughly 4-fold increase in NKG2D ligand levels.

“Our results show that the transfer of NK cells is a possible strategic option to treat B-cell lymphoma,” Dr Mocikat said. “According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity.”

 

 

NK cell destroying a cancer cell

Image by Joshua Strokes

 

Researchers say they have determined how lymphoma cells evade natural killer (NK) cells, and this discovery has revealed potential solutions to the problem.

The team found that NK-cell activation and a second, “triggering” event are both necessary for NK cells to exhibit cytotoxicity in the presence of B-cell lymphoma.

Previous research demonstrated this 2-step process in vitro. Now, researchers have shown that it occurs in vivo.

Dr Ralph Mocikat, of Helmholtz Zentrum München in Munich, Germany, and his colleagues described this research in the European Journal of Immunology.

The team conducted experiments using transplantable tumors, a λ-myc-transgenic model of endogenously arising lymphoma that mimics human Burkitt lymphoma, and mice deficient in the NK group 2 D (NKG2D) receptor.

The experiments showed that NK cells could eliminate lymphoma cells after receiving 2 signals. The first was NK-cell activation, which gave rise to IFN-γ expression.

The researchers found that NK cells could be activated in the presence of MHC class I_low tumor cells or by injecting bone marrow-derived dendritic cells. Previous research had shown that interleukin 2 (IL-2) and IL-15 could activate NK cells.

The second step involved the NKG2D receptor and its ligands. NKG2D ligands are located on the surface of tumor cells and bind to NK cells. The researchers found that, if these ligands are down-regulated, the NK cells cannot carry out cytotoxic activity.

However, the team found they could increase NKG2D ligand levels. They introduced bortezomib to the tumor cell line 291 and saw a roughly 4-fold increase in NKG2D ligand levels.

“Our results show that the transfer of NK cells is a possible strategic option to treat B-cell lymphoma,” Dr Mocikat said. “According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity.”