Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.

The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.

“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”

RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.

Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.

Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.

Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.

“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.

SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.

Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.

The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.

“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”

RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.

Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.

Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.

Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.

“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.

SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.

Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.

The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.

“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”

RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.

Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.

Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.

Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.

“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.

SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

SAN DIEGO – In patients with newly diagnosed acute myeloid leukemia (AML) bearing IDH1 or IDH2 mutations, combinations of either ivosidenib (Tibsovo, for IDH1) or enasidenib (Idhifa, for IDH2) with standard induction and consolidation regimens are safe and well tolerated and are associated with encouraging remission rates, results of a phase 1 trial indicate.

In the open-label, phase 1 trial, ivosidenib plus chemotherapy was associated with elimination of minimal residual disease (MRD) by flow cytometry in 88% of treated patients and with IDH1-mutation clearance in 41% of patients.

Enasidenib plus chemotherapy was associated with elimination of MRD in 45% of patients and with IDH2-mutation clearance in 25% of patients, said Eytan M. Stein, MD, from Memorial Sloan Kettering Cancer Center in New York.

“The overall survival rates are robust, with greater than 75% 1-year survival in both ivosidenib- and enasidenib-treated patients,” he said at the annual meeting of the American Society of Hematology.

Both ivosidenib and enasidenib are approved in the United States for treatment of patients with relapsed or refractory AML bearing either IDH1 or IDH2 mutations, respectively. In this trial, the investigators explored the therapeutic potential of the IDH inhibitors in patients with previously untreated disease.

Dr. Stein and his colleagues investigated combining each of the agents with standard induction therapy with either daunorubicin 60 mg/m² per day or idarubicin 12 mg/m² per day for 3 days, plus cytarabine 200 mg/m² per day for 7 days. Patients with IDH1 mutations received ivosidenib 500 mg once daily, and those with IDH2 mutations received enasidenib 100 mg once daily.

After induction, patients with a complete remission (CR), CR with incomplete recovery of hematologic counts (CRi), or CR with incomplete recovery of platelets (CRp) could receive up to four cycles of consolidation therapy while continuing the IDH inhibitor. Patients who completed consolidation or were ineligible for consolidation could continue on maintenance therapy with their assigned drug until the end of the study.

The drugs were discontinued in patients who went on to hematopoietic stem cell transplant.

The most frequent co-occurring baseline mutations were DNMT3A, NPM1, and NRAS for patients with IDH1 mutations, and DNMT3A, SRSF2, and ASXL1 for patients with IDH2 mutations.

A total of 60 patients were assigned to ivosidenib and chemotherapy and 93 were assigned to enasidenib/chemotherapy. The median patient age was about 63 years in each arm.

All patients in each arm received a least one induction dose and about 48% in each arm received at least some consolidation dosing. In all, 18% of patients in the ivosidenib arm and 19% in the enasidenib arm went on to maintenance.

Treatment discontinuations occurred in 55% of patients in the ivosidenib group and 84% in the enasidenib group. The primary reason for discontinuation included HSCT, adverse events, progressive disease, and death (one and four patients in the respective arms).

Adverse events of interest, regardless of attribution, included the IDH differentiation syndrome in two patients on ivosidenib and one on enasidenib, leukocytosis, QT interval prolongation, and increased blood bilirubin.

The 30-day and 60-day mortality rates were 5% and 8% in the ivosidenib arm and 5% and 9% in the enasidenib arm, respectively.

Best overall response rates (CR+CRi+CRp) among all patients were 80% in the ivosidenib arm and 72% in the enasidenib arm. In each trial arm, the response rates were higher among patients with de novo AML, compared with secondary AML.

Of 12 ivosidenib-treated patients who had IDH1-mutation clearance, 10 had clearance at the end of induction therapy, and 2 achieved clearance during or after consolidation. Of 15 ivosidenib-treated patients who became MRD negative, 12 had achieved it by the end of induction, and 3 became MRD negative during consolidation.

In the enasidenib arm, 15 patients had IDH2 mutation clearance (11 after induction, 4 during consolidation) and 9 became MRD negative (7 after induction and 2 during or after consolidation).

The probability of surviving to 1 year after the start of induction among ivosidenib-treated patients was 79%; the median overall survival had not been reached and was not estimable at the time of data cutoff. The probability of surviving to 1 year among patients in the enasidenib arm was 75%. In this group, too, median overall survival had not been reached.

The clinical benefit of adding either IDH inhibitor to induction, consolidation, and maintenance therapy for patients with newly diagnosed AML with IDH mutations will be further evaluated in a randomized, phase 3 trial, Dr. Stein said.

The study was funded by Agios Pharmaceuticals and Celgene. Dr. Stein reported consulting with those companies and others.

SOURCE: Stein EM et al. ASH 2018, Abstract 560.

SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.

“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.

The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.

Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.

“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.

A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.

Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.

Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.

Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.

The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.

Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).

As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).

“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.

Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.

“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.

In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.

SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.

“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.

The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.

Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.

“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.

A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.

Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.

Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.

Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.

The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.

Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).

As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).

“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.

Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.

“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.

In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.

SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.

“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.

The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.

Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.

“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.

A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.

Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.

Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.

Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.

The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.

Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).

As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).

“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.

Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.

“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.

In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

A crimson November San Diego sunset over the Pacific Ocean. Seeing your parents dance on their 50th wedding anniversary. A stein of cold Oktoberfest beer. Your car, freshly detailed. Your name written in black ink on a Starbucks Pumpkin Latte. A nicely everted surgical wound.

The smile on your daughter’s face when descending the stairs after a huge trick-or-treat score. A perfectly arranged Mayo stand, oh, exactly as you like it. An empty EMR in basket. A flap close on the nose that closes just so.

A Red Sox World series win (again). Lollipop lamb chops sizzling on the grill on a chilly Saturday tailgating morning. The answer to 14 down that leads to all the other answers you’ve desperately been trying to solve. The “ting” sound that Mimosa glasses make toasting Sunday brunch with friends. The next episode of Black Mirror launching automatically. A brilliant orange maple tree against a brilliant blue sky. The fissures on the crust of a still-warm loaf of Italian bread.

An elderly woman, her husband, daughter, and son-in-law who waited weeks and traveled miles to see you because they know you care. And they insist on seeing only you. A man who comes to see you without his wife this time just because he wanted to tell you in person how much they appreciated your care for her in the end. Opening your mailbox to see the September issue of Vogue, waiting for you to tear off the plastic. An as-yet-untouched Sunday New York Times. The sound of wood popping in the fireplace. The string of melted marshmallow down your son’s arm still attached to a s’more at the other end. 7-7-7 on your dollar slot at the casino. Eight-year-old girls at the center of the field celebrating a Sunday morning soccer victory. Departures showing your flight, gate 8, on time.

The smell of incense. The smell of lightly roasting garlic and olive oil. The smell of your wife’s perfume. The smell of wet leaves. The smell of your favorite scented candle. The smell of burning firewood on an early-morning walk in the Rockies. Snow falling. Snow crunching under your feet. Snow melting.

Remembering the uproarious laughter after your belly flop into the pool back in July. Steph Curry shooting a 3 in slow motion. Snoopy floating over 5th Avenue on Thanksgiving morning. The sound of wrapping paper being stuffed into garbage bags when the opening is done. A prior auth letter of approval. The feeling when you turn that first page of a brand-new Stephen King book. The feel of the grip on your fairway wood. Seeing your favorite movie pop up on Amazon Prime. The head massage your stylist gives you when washing your hair. The near pain of a really good massage.

The warmth of a child on your lap. The bark your dog gives when he sees you for the first time today as if it has been a million years. The crack of your favorite beer can opening. The ding when your microwave popcorn is ready. That warm feeling when you realize that, no, you don’t need any filter for that picture, it is ready to post exactly the way it is. The smile on your medical assistant’s face when you hand her a gratitude card. The ping that an email makes when you’re dying to hear back. The pride you feel when you execute a downward-facing dog and the instructor tells everyone to do it just like you. The smell of balsam fir. A podcast episode so good, you sit in your driveway to finish listening. A patient with a delightful British accent. The feel of pasta dough in your hands after adding just the right amount of flour and water so it’s now ready to go. Watching the Red Sox win the World Series (Wait, did I say that already?). The sound of your laptop keyboard clicking away while you write this piece. The feeling that 2019 is going to be your best year ever.



So what are the beautiful things in your life? Sit down right now and list a few (or a lot) of them. I promise it will be a more beautiful place where you are when you’re done.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

A crimson November San Diego sunset over the Pacific Ocean. Seeing your parents dance on their 50th wedding anniversary. A stein of cold Oktoberfest beer. Your car, freshly detailed. Your name written in black ink on a Starbucks Pumpkin Latte. A nicely everted surgical wound.

The smile on your daughter’s face when descending the stairs after a huge trick-or-treat score. A perfectly arranged Mayo stand, oh, exactly as you like it. An empty EMR in basket. A flap close on the nose that closes just so.

A Red Sox World series win (again). Lollipop lamb chops sizzling on the grill on a chilly Saturday tailgating morning. The answer to 14 down that leads to all the other answers you’ve desperately been trying to solve. The “ting” sound that Mimosa glasses make toasting Sunday brunch with friends. The next episode of Black Mirror launching automatically. A brilliant orange maple tree against a brilliant blue sky. The fissures on the crust of a still-warm loaf of Italian bread.

An elderly woman, her husband, daughter, and son-in-law who waited weeks and traveled miles to see you because they know you care. And they insist on seeing only you. A man who comes to see you without his wife this time just because he wanted to tell you in person how much they appreciated your care for her in the end. Opening your mailbox to see the September issue of Vogue, waiting for you to tear off the plastic. An as-yet-untouched Sunday New York Times. The sound of wood popping in the fireplace. The string of melted marshmallow down your son’s arm still attached to a s’more at the other end. 7-7-7 on your dollar slot at the casino. Eight-year-old girls at the center of the field celebrating a Sunday morning soccer victory. Departures showing your flight, gate 8, on time.

The smell of incense. The smell of lightly roasting garlic and olive oil. The smell of your wife’s perfume. The smell of wet leaves. The smell of your favorite scented candle. The smell of burning firewood on an early-morning walk in the Rockies. Snow falling. Snow crunching under your feet. Snow melting.

Remembering the uproarious laughter after your belly flop into the pool back in July. Steph Curry shooting a 3 in slow motion. Snoopy floating over 5th Avenue on Thanksgiving morning. The sound of wrapping paper being stuffed into garbage bags when the opening is done. A prior auth letter of approval. The feeling when you turn that first page of a brand-new Stephen King book. The feel of the grip on your fairway wood. Seeing your favorite movie pop up on Amazon Prime. The head massage your stylist gives you when washing your hair. The near pain of a really good massage.

The warmth of a child on your lap. The bark your dog gives when he sees you for the first time today as if it has been a million years. The crack of your favorite beer can opening. The ding when your microwave popcorn is ready. That warm feeling when you realize that, no, you don’t need any filter for that picture, it is ready to post exactly the way it is. The smile on your medical assistant’s face when you hand her a gratitude card. The ping that an email makes when you’re dying to hear back. The pride you feel when you execute a downward-facing dog and the instructor tells everyone to do it just like you. The smell of balsam fir. A podcast episode so good, you sit in your driveway to finish listening. A patient with a delightful British accent. The feel of pasta dough in your hands after adding just the right amount of flour and water so it’s now ready to go. Watching the Red Sox win the World Series (Wait, did I say that already?). The sound of your laptop keyboard clicking away while you write this piece. The feeling that 2019 is going to be your best year ever.



So what are the beautiful things in your life? Sit down right now and list a few (or a lot) of them. I promise it will be a more beautiful place where you are when you’re done.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

A crimson November San Diego sunset over the Pacific Ocean. Seeing your parents dance on their 50th wedding anniversary. A stein of cold Oktoberfest beer. Your car, freshly detailed. Your name written in black ink on a Starbucks Pumpkin Latte. A nicely everted surgical wound.

The smile on your daughter’s face when descending the stairs after a huge trick-or-treat score. A perfectly arranged Mayo stand, oh, exactly as you like it. An empty EMR in basket. A flap close on the nose that closes just so.

A Red Sox World series win (again). Lollipop lamb chops sizzling on the grill on a chilly Saturday tailgating morning. The answer to 14 down that leads to all the other answers you’ve desperately been trying to solve. The “ting” sound that Mimosa glasses make toasting Sunday brunch with friends. The next episode of Black Mirror launching automatically. A brilliant orange maple tree against a brilliant blue sky. The fissures on the crust of a still-warm loaf of Italian bread.

An elderly woman, her husband, daughter, and son-in-law who waited weeks and traveled miles to see you because they know you care. And they insist on seeing only you. A man who comes to see you without his wife this time just because he wanted to tell you in person how much they appreciated your care for her in the end. Opening your mailbox to see the September issue of Vogue, waiting for you to tear off the plastic. An as-yet-untouched Sunday New York Times. The sound of wood popping in the fireplace. The string of melted marshmallow down your son’s arm still attached to a s’more at the other end. 7-7-7 on your dollar slot at the casino. Eight-year-old girls at the center of the field celebrating a Sunday morning soccer victory. Departures showing your flight, gate 8, on time.

The smell of incense. The smell of lightly roasting garlic and olive oil. The smell of your wife’s perfume. The smell of wet leaves. The smell of your favorite scented candle. The smell of burning firewood on an early-morning walk in the Rockies. Snow falling. Snow crunching under your feet. Snow melting.

Remembering the uproarious laughter after your belly flop into the pool back in July. Steph Curry shooting a 3 in slow motion. Snoopy floating over 5th Avenue on Thanksgiving morning. The sound of wrapping paper being stuffed into garbage bags when the opening is done. A prior auth letter of approval. The feeling when you turn that first page of a brand-new Stephen King book. The feel of the grip on your fairway wood. Seeing your favorite movie pop up on Amazon Prime. The head massage your stylist gives you when washing your hair. The near pain of a really good massage.

The warmth of a child on your lap. The bark your dog gives when he sees you for the first time today as if it has been a million years. The crack of your favorite beer can opening. The ding when your microwave popcorn is ready. That warm feeling when you realize that, no, you don’t need any filter for that picture, it is ready to post exactly the way it is. The smile on your medical assistant’s face when you hand her a gratitude card. The ping that an email makes when you’re dying to hear back. The pride you feel when you execute a downward-facing dog and the instructor tells everyone to do it just like you. The smell of balsam fir. A podcast episode so good, you sit in your driveway to finish listening. A patient with a delightful British accent. The feel of pasta dough in your hands after adding just the right amount of flour and water so it’s now ready to go. Watching the Red Sox win the World Series (Wait, did I say that already?). The sound of your laptop keyboard clicking away while you write this piece. The feeling that 2019 is going to be your best year ever.



So what are the beautiful things in your life? Sit down right now and list a few (or a lot) of them. I promise it will be a more beautiful place where you are when you’re done.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Jack Drescher, MD, joins Lorenzo Norris, MD, to talk about issues surrounding conversion therapy. Dr. Drescher is a psychiatrist and psychoanalyst in private practice in New York City. In this episode he explains issues with the therapy as well as how to treat patients who have undergone this “therapy.”

In 2016, Dr. Drescher and his colleagues authored a report that reviews the history of conversion therapy and offers guidelines for government regulations as well as for other regulatory bodies.

He and his colleagues wrote that “peer-reviewed literature from multiple professional organizations, including the American Psychiatric Association and the American Psychological Association, have found no evidence that conversion therapy treatments result in changes in sexual orientation.” They also noted that there is evidence suggesting that these treatments are harmful.

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Jack Drescher, MD, joins Lorenzo Norris, MD, to talk about issues surrounding conversion therapy. Dr. Drescher is a psychiatrist and psychoanalyst in private practice in New York City. In this episode he explains issues with the therapy as well as how to treat patients who have undergone this “therapy.”

In 2016, Dr. Drescher and his colleagues authored a report that reviews the history of conversion therapy and offers guidelines for government regulations as well as for other regulatory bodies.

He and his colleagues wrote that “peer-reviewed literature from multiple professional organizations, including the American Psychiatric Association and the American Psychological Association, have found no evidence that conversion therapy treatments result in changes in sexual orientation.” They also noted that there is evidence suggesting that these treatments are harmful.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Jack Drescher, MD, joins Lorenzo Norris, MD, to talk about issues surrounding conversion therapy. Dr. Drescher is a psychiatrist and psychoanalyst in private practice in New York City. In this episode he explains issues with the therapy as well as how to treat patients who have undergone this “therapy.”

In 2016, Dr. Drescher and his colleagues authored a report that reviews the history of conversion therapy and offers guidelines for government regulations as well as for other regulatory bodies.

He and his colleagues wrote that “peer-reviewed literature from multiple professional organizations, including the American Psychiatric Association and the American Psychological Association, have found no evidence that conversion therapy treatments result in changes in sexual orientation.” They also noted that there is evidence suggesting that these treatments are harmful.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

One in four patients with type 1 or 2 diabetes reported underusing insulin due to cost. Also today, methotrexate fails to cut cardiovascular events, a single-item scale is effective for assessing sleep quality, and deaths from opioid overdose for inpatients with sickle cell disease do not match those of general inpatients.

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One in four patients with type 1 or 2 diabetes reported underusing insulin due to cost. Also today, methotrexate fails to cut cardiovascular events, a single-item scale is effective for assessing sleep quality, and deaths from opioid overdose for inpatients with sickle cell disease do not match those of general inpatients.

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One in four patients with type 1 or 2 diabetes reported underusing insulin due to cost. Also today, methotrexate fails to cut cardiovascular events, a single-item scale is effective for assessing sleep quality, and deaths from opioid overdose for inpatients with sickle cell disease do not match those of general inpatients.

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In June 2018, the US Department of Veterans Affairs (VA) issued its National Strategy for Preventing Veteran Suicide, 2018-2028. Its 14 goals—many highly innovative—are “to provide a framework for identifying priorities, organizing efforts, and contributing to a national focus on Veteran suicide prevention.”¹

The National Strategy recognizes that suicide prevention requires a 3-pronged approach that includes universal, selective, and targeted strategies because “suicide cannot be prevented by any single strategy.”¹ Even so, the National Strategy does not heed this core tenet. It focuses exclusively on universal, non-VA community-based priorities and efforts. That focus causes a problem because it neglects the other strategies. It also is precarious because in the current era of VA zero sum budgets, increases in 1 domain come from decreases in another. Thus, sole prioritizing of universal community components could divert funds from extant effective VA suicide prevention programs.

Community-based engagement is unquestionably necessary to prevent suicide among all veterans. Even so, a 10-year prospective strategy should build up, not compromise, VA initiatives. The plan would be improved by explicitly bolstering VA programs that are making a vital difference.

Undercutting VA Suicide Prevention

As my recent review in Federal Practitioner documented, VA’s multiple levels of evidenced-based suicide prevention practices are pre-eminent in the field.² The VA’s innovative use of predictive analytics to identify and intervene with at-risk individuals is more advanced than anything available in the community. For older veterans who constitute the majority of veterans and the majority of veteran suicides, the VA has more comprehensive and integrated mental health care services than those found in community-based care systems. The embedding of suicide prevention coordinators at every VA facility is unparalleled.

But one would never know about such quality from the National Strategy document: The VA is barely mentioned. The report never advocates for strengthening—or even maintaining—VA’s resources, programs, and efforts. It never recommends that eligible veterans be connected to VA mental health services.

The strategy observes that employment and housing are keys that protect against suicide risk. It does not, however, call for boosting and resourcing VA’s integrated approach that wraps in social services better than does any other program. Similarly, it acknowledges the role of family involvement in mitigating risk but does not propose expanding VA treatments to improve relationship well-being, leaving these services to the private sector.

The National Strategy expands on the recent suicide prevention executive order (EO) for supporting veterans during their transition from military to civilian life. Yet the EO has no funding allocated to this critical initiative. The National Strategy has the same shortcoming. In failing to advocate for more funds to pay for vastly enhanced outreach and intervention, the plan could drain the VA of existing resources needed to maintain its high-quality, suicide prevention services.

First Step: Define the Problem

The National Strategy wisely specifies that the initial step in any suicide prevention effort should be to “define the problem. This involves collecting data to determine the ‘who,’ ‘what,’ ‘where,’ ‘when,’ and ‘how’ of suicide deaths.” Then, “identify risk and protective factors.”

Yet the report doesn’t follow its own advice. Although little is known about the 14 of 20 veterans who die by suicide daily who are not recent users of VA health services, the National Strategy foregoes the necessity of first ascertaining crucial factors, including whether those veterans were (a) eligible for VA care; (b) receiving any mental health or substance use treatment; and (c) going through life crises, etc. What’s needed before reallocating funds to community-based programs is for Congress to finance a post-suicide, case-by-case study of these veteran decedents who did not use VA.

Proceeding in this manner has 2 benefits. First, it would allow initiatives to be targeted. Second, it could preserve funds for successful VA programs that otherwise might be cut to pay for private sector programs.

A Positive Starting Point

There are many positive components of the National Strategy for Preventing Veteran Suicide that will make a difference. That said, they fall short of their potential. The following are suggestions that could strengthen the VA’s plan.

First, given the overwhelming use of firearms by veterans who die by suicide, the National Strategy acknowledges that an effective prevention policy must attend to this factor. It prudently calls for expansion of firearm safety/suicide prevention collaboration with firearm owners, firearm dealers, shooting clubs, and gun/hunting organizations. This will help ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and has no antifirearm bias.

Nothing would be more useful in diminishing suicide than correcting the false belief among many veterans that “the VA wants to take away our guns.” If that misperception were replaced with an accurate message, not only would more at-risk veterans seek out VA mental health care, more veterans/families/friends would adopt a new cultural norm akin to buddies talk to vets in crisis about safely storing guns. Establishing a workgroup with gun constituency collaborators could spearhead such a shift.

Second, although, the National Strategy emphasizes the benefits of using peer supports, peers currently express qualms that they have too little expertise intervening with this vulnerable population. Peers could be given extensive training and continued supervision in suicide prevention techniques.

Third, the National Strategy calls for expanded use of big data predictive analytics, whose initial implementation has shown great promise. However, it fails to mention that this approach depends on linked electronic health records and therefore best succeeds for at-risk veterans within VA but not in insulated community care. 

Fourth, the National Strategy recognizes that reshaping media and entertainment portrayals could help prevent veteran suicide. Yet it ignores the importance of correcting the sullied narrative about the VA. The disproportionate negative image contributes to veterans’ reticence to seek VA health care. One simple solution would be to require that service members readying to transition to civilian life be informed about the superior nature of VA mental health care. Another is to provide the media with positive VA stories more routinely.

Fifth, the National Strategy suggests that enhanced community care guidelines be developed, but it never recommends that community partners should equal VA’s standards. Those providers should be mandated to conduct the same root cause analyses and comprehensive documentation of suicide risk assessments that VA does.

Conclusion

With zero sum department budgets, the National Strategy’s exclusive priority on public health, community-based initiatives could undercut VA successes. An amended plan that explicitly supports and further strengthens successful VA suicide prevention programs is warranted.

In June 2018, the US Department of Veterans Affairs (VA) issued its National Strategy for Preventing Veteran Suicide, 2018-2028. Its 14 goals—many highly innovative—are “to provide a framework for identifying priorities, organizing efforts, and contributing to a national focus on Veteran suicide prevention.”¹

The National Strategy recognizes that suicide prevention requires a 3-pronged approach that includes universal, selective, and targeted strategies because “suicide cannot be prevented by any single strategy.”¹ Even so, the National Strategy does not heed this core tenet. It focuses exclusively on universal, non-VA community-based priorities and efforts. That focus causes a problem because it neglects the other strategies. It also is precarious because in the current era of VA zero sum budgets, increases in 1 domain come from decreases in another. Thus, sole prioritizing of universal community components could divert funds from extant effective VA suicide prevention programs.

Community-based engagement is unquestionably necessary to prevent suicide among all veterans. Even so, a 10-year prospective strategy should build up, not compromise, VA initiatives. The plan would be improved by explicitly bolstering VA programs that are making a vital difference.

Undercutting VA Suicide Prevention

As my recent review in Federal Practitioner documented, VA’s multiple levels of evidenced-based suicide prevention practices are pre-eminent in the field.² The VA’s innovative use of predictive analytics to identify and intervene with at-risk individuals is more advanced than anything available in the community. For older veterans who constitute the majority of veterans and the majority of veteran suicides, the VA has more comprehensive and integrated mental health care services than those found in community-based care systems. The embedding of suicide prevention coordinators at every VA facility is unparalleled.

But one would never know about such quality from the National Strategy document: The VA is barely mentioned. The report never advocates for strengthening—or even maintaining—VA’s resources, programs, and efforts. It never recommends that eligible veterans be connected to VA mental health services.

The strategy observes that employment and housing are keys that protect against suicide risk. It does not, however, call for boosting and resourcing VA’s integrated approach that wraps in social services better than does any other program. Similarly, it acknowledges the role of family involvement in mitigating risk but does not propose expanding VA treatments to improve relationship well-being, leaving these services to the private sector.

The National Strategy expands on the recent suicide prevention executive order (EO) for supporting veterans during their transition from military to civilian life. Yet the EO has no funding allocated to this critical initiative. The National Strategy has the same shortcoming. In failing to advocate for more funds to pay for vastly enhanced outreach and intervention, the plan could drain the VA of existing resources needed to maintain its high-quality, suicide prevention services.

First Step: Define the Problem

The National Strategy wisely specifies that the initial step in any suicide prevention effort should be to “define the problem. This involves collecting data to determine the ‘who,’ ‘what,’ ‘where,’ ‘when,’ and ‘how’ of suicide deaths.” Then, “identify risk and protective factors.”

Yet the report doesn’t follow its own advice. Although little is known about the 14 of 20 veterans who die by suicide daily who are not recent users of VA health services, the National Strategy foregoes the necessity of first ascertaining crucial factors, including whether those veterans were (a) eligible for VA care; (b) receiving any mental health or substance use treatment; and (c) going through life crises, etc. What’s needed before reallocating funds to community-based programs is for Congress to finance a post-suicide, case-by-case study of these veteran decedents who did not use VA.

Proceeding in this manner has 2 benefits. First, it would allow initiatives to be targeted. Second, it could preserve funds for successful VA programs that otherwise might be cut to pay for private sector programs.

A Positive Starting Point

There are many positive components of the National Strategy for Preventing Veteran Suicide that will make a difference. That said, they fall short of their potential. The following are suggestions that could strengthen the VA’s plan.

First, given the overwhelming use of firearms by veterans who die by suicide, the National Strategy acknowledges that an effective prevention policy must attend to this factor. It prudently calls for expansion of firearm safety/suicide prevention collaboration with firearm owners, firearm dealers, shooting clubs, and gun/hunting organizations. This will help ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and has no antifirearm bias.

Nothing would be more useful in diminishing suicide than correcting the false belief among many veterans that “the VA wants to take away our guns.” If that misperception were replaced with an accurate message, not only would more at-risk veterans seek out VA mental health care, more veterans/families/friends would adopt a new cultural norm akin to buddies talk to vets in crisis about safely storing guns. Establishing a workgroup with gun constituency collaborators could spearhead such a shift.

Second, although, the National Strategy emphasizes the benefits of using peer supports, peers currently express qualms that they have too little expertise intervening with this vulnerable population. Peers could be given extensive training and continued supervision in suicide prevention techniques.

Third, the National Strategy calls for expanded use of big data predictive analytics, whose initial implementation has shown great promise. However, it fails to mention that this approach depends on linked electronic health records and therefore best succeeds for at-risk veterans within VA but not in insulated community care. 

Fourth, the National Strategy recognizes that reshaping media and entertainment portrayals could help prevent veteran suicide. Yet it ignores the importance of correcting the sullied narrative about the VA. The disproportionate negative image contributes to veterans’ reticence to seek VA health care. One simple solution would be to require that service members readying to transition to civilian life be informed about the superior nature of VA mental health care. Another is to provide the media with positive VA stories more routinely.

Fifth, the National Strategy suggests that enhanced community care guidelines be developed, but it never recommends that community partners should equal VA’s standards. Those providers should be mandated to conduct the same root cause analyses and comprehensive documentation of suicide risk assessments that VA does.

Conclusion

With zero sum department budgets, the National Strategy’s exclusive priority on public health, community-based initiatives could undercut VA successes. An amended plan that explicitly supports and further strengthens successful VA suicide prevention programs is warranted.

In June 2018, the US Department of Veterans Affairs (VA) issued its National Strategy for Preventing Veteran Suicide, 2018-2028. Its 14 goals—many highly innovative—are “to provide a framework for identifying priorities, organizing efforts, and contributing to a national focus on Veteran suicide prevention.”¹

The National Strategy recognizes that suicide prevention requires a 3-pronged approach that includes universal, selective, and targeted strategies because “suicide cannot be prevented by any single strategy.”¹ Even so, the National Strategy does not heed this core tenet. It focuses exclusively on universal, non-VA community-based priorities and efforts. That focus causes a problem because it neglects the other strategies. It also is precarious because in the current era of VA zero sum budgets, increases in 1 domain come from decreases in another. Thus, sole prioritizing of universal community components could divert funds from extant effective VA suicide prevention programs.

Community-based engagement is unquestionably necessary to prevent suicide among all veterans. Even so, a 10-year prospective strategy should build up, not compromise, VA initiatives. The plan would be improved by explicitly bolstering VA programs that are making a vital difference.

Undercutting VA Suicide Prevention

As my recent review in Federal Practitioner documented, VA’s multiple levels of evidenced-based suicide prevention practices are pre-eminent in the field.² The VA’s innovative use of predictive analytics to identify and intervene with at-risk individuals is more advanced than anything available in the community. For older veterans who constitute the majority of veterans and the majority of veteran suicides, the VA has more comprehensive and integrated mental health care services than those found in community-based care systems. The embedding of suicide prevention coordinators at every VA facility is unparalleled.

But one would never know about such quality from the National Strategy document: The VA is barely mentioned. The report never advocates for strengthening—or even maintaining—VA’s resources, programs, and efforts. It never recommends that eligible veterans be connected to VA mental health services.

The strategy observes that employment and housing are keys that protect against suicide risk. It does not, however, call for boosting and resourcing VA’s integrated approach that wraps in social services better than does any other program. Similarly, it acknowledges the role of family involvement in mitigating risk but does not propose expanding VA treatments to improve relationship well-being, leaving these services to the private sector.

The National Strategy expands on the recent suicide prevention executive order (EO) for supporting veterans during their transition from military to civilian life. Yet the EO has no funding allocated to this critical initiative. The National Strategy has the same shortcoming. In failing to advocate for more funds to pay for vastly enhanced outreach and intervention, the plan could drain the VA of existing resources needed to maintain its high-quality, suicide prevention services.

First Step: Define the Problem

The National Strategy wisely specifies that the initial step in any suicide prevention effort should be to “define the problem. This involves collecting data to determine the ‘who,’ ‘what,’ ‘where,’ ‘when,’ and ‘how’ of suicide deaths.” Then, “identify risk and protective factors.”

Yet the report doesn’t follow its own advice. Although little is known about the 14 of 20 veterans who die by suicide daily who are not recent users of VA health services, the National Strategy foregoes the necessity of first ascertaining crucial factors, including whether those veterans were (a) eligible for VA care; (b) receiving any mental health or substance use treatment; and (c) going through life crises, etc. What’s needed before reallocating funds to community-based programs is for Congress to finance a post-suicide, case-by-case study of these veteran decedents who did not use VA.

Proceeding in this manner has 2 benefits. First, it would allow initiatives to be targeted. Second, it could preserve funds for successful VA programs that otherwise might be cut to pay for private sector programs.

A Positive Starting Point

There are many positive components of the National Strategy for Preventing Veteran Suicide that will make a difference. That said, they fall short of their potential. The following are suggestions that could strengthen the VA’s plan.

First, given the overwhelming use of firearms by veterans who die by suicide, the National Strategy acknowledges that an effective prevention policy must attend to this factor. It prudently calls for expansion of firearm safety/suicide prevention collaboration with firearm owners, firearm dealers, shooting clubs, and gun/hunting organizations. This will help ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and has no antifirearm bias.

Nothing would be more useful in diminishing suicide than correcting the false belief among many veterans that “the VA wants to take away our guns.” If that misperception were replaced with an accurate message, not only would more at-risk veterans seek out VA mental health care, more veterans/families/friends would adopt a new cultural norm akin to buddies talk to vets in crisis about safely storing guns. Establishing a workgroup with gun constituency collaborators could spearhead such a shift.

Second, although, the National Strategy emphasizes the benefits of using peer supports, peers currently express qualms that they have too little expertise intervening with this vulnerable population. Peers could be given extensive training and continued supervision in suicide prevention techniques.

Third, the National Strategy calls for expanded use of big data predictive analytics, whose initial implementation has shown great promise. However, it fails to mention that this approach depends on linked electronic health records and therefore best succeeds for at-risk veterans within VA but not in insulated community care. 

Fourth, the National Strategy recognizes that reshaping media and entertainment portrayals could help prevent veteran suicide. Yet it ignores the importance of correcting the sullied narrative about the VA. The disproportionate negative image contributes to veterans’ reticence to seek VA health care. One simple solution would be to require that service members readying to transition to civilian life be informed about the superior nature of VA mental health care. Another is to provide the media with positive VA stories more routinely.

Fifth, the National Strategy suggests that enhanced community care guidelines be developed, but it never recommends that community partners should equal VA’s standards. Those providers should be mandated to conduct the same root cause analyses and comprehensive documentation of suicide risk assessments that VA does.

Conclusion

With zero sum department budgets, the National Strategy’s exclusive priority on public health, community-based initiatives could undercut VA successes. An amended plan that explicitly supports and further strengthens successful VA suicide prevention programs is warranted.

Photo by Jen Smith

SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.

In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).

Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.

Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).

The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.

Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.

Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.

Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).

The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.

Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.

Survival

The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.

In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.

“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.

The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.

The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.

In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).

There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.

In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.

He disclosed no conflicts of interest. 

* Data in the presentation differ from the abstract.

Photo by Jen Smith

SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.

In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).

Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.

Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).

The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.

Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.

Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.

Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).

The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.

Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.

Survival

The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.

In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.

“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.

The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.

The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.

In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).

There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.

In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.

He disclosed no conflicts of interest. 

* Data in the presentation differ from the abstract.

Photo by Jen Smith

SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.

In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).

Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.

Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).

The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.

Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.

Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.

Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).

The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.

Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.

Survival

The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.

In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.

“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.

The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.

The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.

In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).

There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.

In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.

He disclosed no conflicts of interest. 

* Data in the presentation differ from the abstract.

©ASH/Scott Morgan 2018

SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.

Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.

However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.

Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).

ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).

The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.

One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.

Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT)—48% and 47%, respectively
• PE only—44% and 39%, respectively
• PE with DVT—12% in both arms
• DVT only—37% and 35%, respectively
• Lower extremity DVT—31% and 34%, respectively
• Upper extremity DVT—17% and 14%, respectively
• Cerebral venous thrombosis (VT)—1% and 0%, respectively
• Splanchnic VT—8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:

• Be concerned about excessive bruising
• Find anticoagulant treatment a burden or difficult to carry out
• Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.

Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).

“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

*Data in the presentation differ from the abstract.

©ASH/Scott Morgan 2018

SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.

Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.

However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.

Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).

ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).

The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.

One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.

Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT)—48% and 47%, respectively
• PE only—44% and 39%, respectively
• PE with DVT—12% in both arms
• DVT only—37% and 35%, respectively
• Lower extremity DVT—31% and 34%, respectively
• Upper extremity DVT—17% and 14%, respectively
• Cerebral venous thrombosis (VT)—1% and 0%, respectively
• Splanchnic VT—8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:

• Be concerned about excessive bruising
• Find anticoagulant treatment a burden or difficult to carry out
• Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.

Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).

“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

*Data in the presentation differ from the abstract.

©ASH/Scott Morgan 2018

SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.

Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.

However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.

Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).

ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).

The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.

One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.

Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT)—48% and 47%, respectively
• PE only—44% and 39%, respectively
• PE with DVT—12% in both arms
• DVT only—37% and 35%, respectively
• Lower extremity DVT—31% and 34%, respectively
• Upper extremity DVT—17% and 14%, respectively
• Cerebral venous thrombosis (VT)—1% and 0%, respectively
• Splanchnic VT—8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:

• Be concerned about excessive bruising
• Find anticoagulant treatment a burden or difficult to carry out
• Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.

Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).

“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

*Data in the presentation differ from the abstract.