Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Background: Head and neck (HAN) cancer is diagnosed in more than 50,000 Americans annually and is the third most common malignancy in the Veteran patient population. There are > 185,000 American HAN cancer survivors. The comprehensive nature of this disease causes challenges from diagnosis through survivorship. A lack of patient navigation program (PNP) for patients with HAN cancer often lead to fragmented care, delay in initiation of treatment, increased healthcare cost, poor cancer outcome, and a decrease in patient satisfaction.

Purpose: To improve care outcomes among patients with HAN cancer through the implementation of the PNP. Specifically, the program is targeted towards providing holistic patient-centered care, eliminating fragmented care and delays, and decreasing emotional distress and healthcare cost.

Method: In the First Phase, we conducted a need assessment for the PNP. In the Second Phase, we implemented the PNP in 2015 using current evidence and Deming’s (1993) Plan-Do-Study-Act (PDSA) model. During the Implementation Phase of the PNP, we developed a clinical algorithm and order set. We also strengthened our partnership with Non-VA Care Coordination
to expedite community care.

Outcomes: The PNP has served 140 Veterans with well over 500 clinical visits. Consistent with our expectation, the program has resulted in improved oncology infrastructure and timeliness of care. For instance, before the program, there was an average of 16 weeks from suspicion to initiation of treatment. After PNP implementation, the process now takes 4 to 6 weeks. The PNP has eliminated repeat computerized axial tomography, and thus, decreasing healthcare cost by $262,500 annually. Besides its economic impact, the PNP has also led to improved patient and provider satisfaction.

Clinical Implications: Overall, the PNP is a robust patientcentered care program which provides holistic care to patients from cancer suspicion to treatment initiation. Although the PNP continues to evolve, its implementation in BPVAHCS has had a significant impact in the care of HAN cancer patients. Due to the success of the current PNP, BPVAHCS is planning to include all cancer sites by 2020.

Background: Head and neck (HAN) cancer is diagnosed in more than 50,000 Americans annually and is the third most common malignancy in the Veteran patient population. There are > 185,000 American HAN cancer survivors. The comprehensive nature of this disease causes challenges from diagnosis through survivorship. A lack of patient navigation program (PNP) for patients with HAN cancer often lead to fragmented care, delay in initiation of treatment, increased healthcare cost, poor cancer outcome, and a decrease in patient satisfaction.

Purpose: To improve care outcomes among patients with HAN cancer through the implementation of the PNP. Specifically, the program is targeted towards providing holistic patient-centered care, eliminating fragmented care and delays, and decreasing emotional distress and healthcare cost.

Method: In the First Phase, we conducted a need assessment for the PNP. In the Second Phase, we implemented the PNP in 2015 using current evidence and Deming’s (1993) Plan-Do-Study-Act (PDSA) model. During the Implementation Phase of the PNP, we developed a clinical algorithm and order set. We also strengthened our partnership with Non-VA Care Coordination
to expedite community care.

Outcomes: The PNP has served 140 Veterans with well over 500 clinical visits. Consistent with our expectation, the program has resulted in improved oncology infrastructure and timeliness of care. For instance, before the program, there was an average of 16 weeks from suspicion to initiation of treatment. After PNP implementation, the process now takes 4 to 6 weeks. The PNP has eliminated repeat computerized axial tomography, and thus, decreasing healthcare cost by $262,500 annually. Besides its economic impact, the PNP has also led to improved patient and provider satisfaction.

Clinical Implications: Overall, the PNP is a robust patientcentered care program which provides holistic care to patients from cancer suspicion to treatment initiation. Although the PNP continues to evolve, its implementation in BPVAHCS has had a significant impact in the care of HAN cancer patients. Due to the success of the current PNP, BPVAHCS is planning to include all cancer sites by 2020.

Background: Head and neck (HAN) cancer is diagnosed in more than 50,000 Americans annually and is the third most common malignancy in the Veteran patient population. There are > 185,000 American HAN cancer survivors. The comprehensive nature of this disease causes challenges from diagnosis through survivorship. A lack of patient navigation program (PNP) for patients with HAN cancer often lead to fragmented care, delay in initiation of treatment, increased healthcare cost, poor cancer outcome, and a decrease in patient satisfaction.

Purpose: To improve care outcomes among patients with HAN cancer through the implementation of the PNP. Specifically, the program is targeted towards providing holistic patient-centered care, eliminating fragmented care and delays, and decreasing emotional distress and healthcare cost.

Method: In the First Phase, we conducted a need assessment for the PNP. In the Second Phase, we implemented the PNP in 2015 using current evidence and Deming’s (1993) Plan-Do-Study-Act (PDSA) model. During the Implementation Phase of the PNP, we developed a clinical algorithm and order set. We also strengthened our partnership with Non-VA Care Coordination
to expedite community care.

Outcomes: The PNP has served 140 Veterans with well over 500 clinical visits. Consistent with our expectation, the program has resulted in improved oncology infrastructure and timeliness of care. For instance, before the program, there was an average of 16 weeks from suspicion to initiation of treatment. After PNP implementation, the process now takes 4 to 6 weeks. The PNP has eliminated repeat computerized axial tomography, and thus, decreasing healthcare cost by $262,500 annually. Besides its economic impact, the PNP has also led to improved patient and provider satisfaction.

Clinical Implications: Overall, the PNP is a robust patientcentered care program which provides holistic care to patients from cancer suspicion to treatment initiation. Although the PNP continues to evolve, its implementation in BPVAHCS has had a significant impact in the care of HAN cancer patients. Due to the success of the current PNP, BPVAHCS is planning to include all cancer sites by 2020.

CTPA showing PE

Image courtesy of

Medical College of Georgia

ROME—A new study suggests the YEARS algorithm may provide a simple method for ruling out pulmonary embolism (PE) and therefore reduce the need for computed tomography pulmonary angiography (CTPA).

“[The YEARS algorithm] can replace current diagnostic algorithms, which, although safe and accurate, are often not used in busy emergency departments because they are too complex,” said study investigator Tom Van der Hulle, MD, of Leiden University Medical Center in the Netherlands.

“The advantage of the YEARS algorithm over existing algorithms is a 14% reduction in the need for CTPA imaging and, with that, reduced potential for radiation-induced harm and overdiagnosis.”

Dr Van der Hulle described his team’s results with the YEARS algorithm at ESC Congress 2016 (abstract 5727).

About the algorithm

The YEARS algorithm consists of a blood test and 3 items of the original Wells rule.

Patients presenting to the emergency department can be evaluated based on:

1. Clinical signs of deep vein thrombosis (eg, swelling, edema)
2. Hemoptysis
3. Whether the clinician considers PE to be “the most likely diagnosis.”

Using this information combined with results of a blood test measuring D-dimer, clinicians can either exclude PE or recommend CTPA for definitive diagnosis.

Based on the algorithm, PE can be excluded in patients who have either:

• None of the 3 YEARS items and a D-dimer level <1000 ng/mL
• One or more YEARS items and a D-dimer level <500 ng/mL.

Testing the algorithm

Dr Van der Hulle and his colleagues prospectively evaluated the YEARS algorithm in 3465 patients. They had a mean age of 53, and 88% were outpatients.

If patients did not have PE excluded via the algorithm, they went on to CTPA. If PE was confirmed, patients received anticoagulant therapy.

Most of the patients in whom PE was excluded (either by algorithm or CTPA) were left untreated and were followed for 3 months, although 60 patients who had PE excluded received anticoagulants anyway.

In all, 1651 patients had PE excluded with the YEARS algorithm, and 1633 of them did not receive anticoagulation.

A total of 1814 patients did not have PE excluded via the YEARS algorithm and went on to CTPA. Of these patients, 456 had PE, 42 had PE excluded via CTPA but received anticoagulation, and 1316 had PE excluded but did not receive anticoagulation.

Five patients were lost to follow-up—4 with PE excluded via the YEARS algorithm and 1 who went on to CTPA.

Patient outcomes

The primary outcome of this study was the 3-month incidence of symptomatic venous thromboembolism (VTE).

A total of 2944 patients were evaluable (because they had PE excluded, did not receive anticoagulation, and were not lost to follow-up)—1629 who had PE excluded via the YEARS algorithm and 1315 who had PE excluded via CTPA.

Symptomatic VTE occurred in 0.61% of all evaluable patients, 0.43% of patients who had PE excluded via YEARS, and 0.84% of patients who had PE excluded via CTPA.

Fatal PE occurred in 0.20% of all evaluable patients, 0.12% of patients who had PE excluded via YEARS, and 0.30% of patients who had PE excluded via CTPA.

“This is fully in line with that observed in studies using traditional, sequential algorithms such as the 2-level Wells score and a fixed cut-off level of D-dimer of 500 ng/mL,” Dr Van der Hulle said.

“Using the YEARS algorithm, CTPA was not indicated in 48% of our patients at baseline, but this would have been only 34% of patients using the traditional algorithm. This shows that the YEARS algorithm can safely exclude PE and resulted in an absolute reduction of required CTPA of 14%.”

“We expect that the YEARS algorithm can be easily implemented outside the participating study sites and that these safety and efficacy outcomes are representative of what could be expected in regular clinical settings.”

CTPA showing PE

Image courtesy of

Medical College of Georgia

ROME—A new study suggests the YEARS algorithm may provide a simple method for ruling out pulmonary embolism (PE) and therefore reduce the need for computed tomography pulmonary angiography (CTPA).

“[The YEARS algorithm] can replace current diagnostic algorithms, which, although safe and accurate, are often not used in busy emergency departments because they are too complex,” said study investigator Tom Van der Hulle, MD, of Leiden University Medical Center in the Netherlands.

“The advantage of the YEARS algorithm over existing algorithms is a 14% reduction in the need for CTPA imaging and, with that, reduced potential for radiation-induced harm and overdiagnosis.”

Dr Van der Hulle described his team’s results with the YEARS algorithm at ESC Congress 2016 (abstract 5727).

About the algorithm

The YEARS algorithm consists of a blood test and 3 items of the original Wells rule.

Patients presenting to the emergency department can be evaluated based on:

1. Clinical signs of deep vein thrombosis (eg, swelling, edema)
2. Hemoptysis
3. Whether the clinician considers PE to be “the most likely diagnosis.”

Using this information combined with results of a blood test measuring D-dimer, clinicians can either exclude PE or recommend CTPA for definitive diagnosis.

Based on the algorithm, PE can be excluded in patients who have either:

• None of the 3 YEARS items and a D-dimer level <1000 ng/mL
• One or more YEARS items and a D-dimer level <500 ng/mL.

Testing the algorithm

Dr Van der Hulle and his colleagues prospectively evaluated the YEARS algorithm in 3465 patients. They had a mean age of 53, and 88% were outpatients.

If patients did not have PE excluded via the algorithm, they went on to CTPA. If PE was confirmed, patients received anticoagulant therapy.

Most of the patients in whom PE was excluded (either by algorithm or CTPA) were left untreated and were followed for 3 months, although 60 patients who had PE excluded received anticoagulants anyway.

In all, 1651 patients had PE excluded with the YEARS algorithm, and 1633 of them did not receive anticoagulation.

A total of 1814 patients did not have PE excluded via the YEARS algorithm and went on to CTPA. Of these patients, 456 had PE, 42 had PE excluded via CTPA but received anticoagulation, and 1316 had PE excluded but did not receive anticoagulation.

Five patients were lost to follow-up—4 with PE excluded via the YEARS algorithm and 1 who went on to CTPA.

Patient outcomes

The primary outcome of this study was the 3-month incidence of symptomatic venous thromboembolism (VTE).

A total of 2944 patients were evaluable (because they had PE excluded, did not receive anticoagulation, and were not lost to follow-up)—1629 who had PE excluded via the YEARS algorithm and 1315 who had PE excluded via CTPA.

Symptomatic VTE occurred in 0.61% of all evaluable patients, 0.43% of patients who had PE excluded via YEARS, and 0.84% of patients who had PE excluded via CTPA.

Fatal PE occurred in 0.20% of all evaluable patients, 0.12% of patients who had PE excluded via YEARS, and 0.30% of patients who had PE excluded via CTPA.

“This is fully in line with that observed in studies using traditional, sequential algorithms such as the 2-level Wells score and a fixed cut-off level of D-dimer of 500 ng/mL,” Dr Van der Hulle said.

“Using the YEARS algorithm, CTPA was not indicated in 48% of our patients at baseline, but this would have been only 34% of patients using the traditional algorithm. This shows that the YEARS algorithm can safely exclude PE and resulted in an absolute reduction of required CTPA of 14%.”

“We expect that the YEARS algorithm can be easily implemented outside the participating study sites and that these safety and efficacy outcomes are representative of what could be expected in regular clinical settings.”

CTPA showing PE

Image courtesy of

Medical College of Georgia

ROME—A new study suggests the YEARS algorithm may provide a simple method for ruling out pulmonary embolism (PE) and therefore reduce the need for computed tomography pulmonary angiography (CTPA).

“[The YEARS algorithm] can replace current diagnostic algorithms, which, although safe and accurate, are often not used in busy emergency departments because they are too complex,” said study investigator Tom Van der Hulle, MD, of Leiden University Medical Center in the Netherlands.

“The advantage of the YEARS algorithm over existing algorithms is a 14% reduction in the need for CTPA imaging and, with that, reduced potential for radiation-induced harm and overdiagnosis.”

Dr Van der Hulle described his team’s results with the YEARS algorithm at ESC Congress 2016 (abstract 5727).

About the algorithm

The YEARS algorithm consists of a blood test and 3 items of the original Wells rule.

Patients presenting to the emergency department can be evaluated based on:

1. Clinical signs of deep vein thrombosis (eg, swelling, edema)
2. Hemoptysis
3. Whether the clinician considers PE to be “the most likely diagnosis.”

Using this information combined with results of a blood test measuring D-dimer, clinicians can either exclude PE or recommend CTPA for definitive diagnosis.

Based on the algorithm, PE can be excluded in patients who have either:

• None of the 3 YEARS items and a D-dimer level <1000 ng/mL
• One or more YEARS items and a D-dimer level <500 ng/mL.

Testing the algorithm

Dr Van der Hulle and his colleagues prospectively evaluated the YEARS algorithm in 3465 patients. They had a mean age of 53, and 88% were outpatients.

If patients did not have PE excluded via the algorithm, they went on to CTPA. If PE was confirmed, patients received anticoagulant therapy.

Most of the patients in whom PE was excluded (either by algorithm or CTPA) were left untreated and were followed for 3 months, although 60 patients who had PE excluded received anticoagulants anyway.

In all, 1651 patients had PE excluded with the YEARS algorithm, and 1633 of them did not receive anticoagulation.

A total of 1814 patients did not have PE excluded via the YEARS algorithm and went on to CTPA. Of these patients, 456 had PE, 42 had PE excluded via CTPA but received anticoagulation, and 1316 had PE excluded but did not receive anticoagulation.

Five patients were lost to follow-up—4 with PE excluded via the YEARS algorithm and 1 who went on to CTPA.

Patient outcomes

The primary outcome of this study was the 3-month incidence of symptomatic venous thromboembolism (VTE).

A total of 2944 patients were evaluable (because they had PE excluded, did not receive anticoagulation, and were not lost to follow-up)—1629 who had PE excluded via the YEARS algorithm and 1315 who had PE excluded via CTPA.

Symptomatic VTE occurred in 0.61% of all evaluable patients, 0.43% of patients who had PE excluded via YEARS, and 0.84% of patients who had PE excluded via CTPA.

Fatal PE occurred in 0.20% of all evaluable patients, 0.12% of patients who had PE excluded via YEARS, and 0.30% of patients who had PE excluded via CTPA.

“This is fully in line with that observed in studies using traditional, sequential algorithms such as the 2-level Wells score and a fixed cut-off level of D-dimer of 500 ng/mL,” Dr Van der Hulle said.

“Using the YEARS algorithm, CTPA was not indicated in 48% of our patients at baseline, but this would have been only 34% of patients using the traditional algorithm. This shows that the YEARS algorithm can safely exclude PE and resulted in an absolute reduction of required CTPA of 14%.”

“We expect that the YEARS algorithm can be easily implemented outside the participating study sites and that these safety and efficacy outcomes are representative of what could be expected in regular clinical settings.”

Warfarin tablets

ROME—The novel oral anticoagulant edoxaban is a feasible treatment option for patients with atrial fibrillation (AF) who need anticoagulation before cardioversion, according to researchers.

Results of the ENSURE-AF trial suggest edoxaban is “an effective and safe alternative” to standard therapy with warfarin and enoxaparin and may allow for prompt cardioversion with transesophageal echocardiography (TEE), said Andreas Goette, MD, of St. Vincenz-Hospital in Paderborn, Germany.

“These results may have important clinical implications for newly diagnosed, non-anticoagulated AF patients undergoing cardioversion,” Dr Goette noted.

“According to the study protocol, a newly diagnosed, non-anticoagulated AF patient was started on edoxaban, and the cardioversion procedure was scheduled as early as 2 hours following the start of treatment, when applying a TEE-guided approach.”

Dr Goette presented results from ENSURE-AF at ESC Congress 2016 (abstract 5715). The data were simultaneously published in The Lancet. The study was supported by Daiichi Sankyo.

This phase 3b study included 2199 patients with documented non-valvular AF who were scheduled for electrical cardioversion after anticoagulation therapy.

Patients were randomized to receive edoxaban (n=1095) or warfarin with enoxaparin bridging (n=1104). Edoxaban was dosed at 60 mg once daily, but the dose was reduced to 30 mg if one or more of the following factors were present: renal impairment, low body weight, or concomitant use of certain P-glycoprotein inhibitors.

Patients were stratified according to the cardioversion approach (TEE or non-TEE), a patient’s prior experience taking anticoagulants at the time of randomization (ie, anticoagulant-experienced or naïve), and edoxaban dose (60 mg or 30 mg). Patients were randomized in a 1:1 ratio to 2 treatment groups within each stratum.

The primary efficacy endpoint was the composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death at day 28.

This endpoint occurred at a comparable rate in both treatment arms—0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (odds ratio [OR]=0.46; 95% CI, 0.12–1.43).

The primary safety endpoint was the composite of major and clinically relevant non-major bleeding events at 30 days.

This endpoint also occurred at a comparable rate in both arms—1.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (OR=1.48; 95% CI, 0.64–3.55).

The result for the net clinical outcome—a composite of stroke, systemic embolic event, myocardial infarction, cardiovascular mortality, and major bleeding—was 0.7% in the edoxaban arm and 1.4% in the enoxaparin/warfarin arm (OR=0.50; 95% CI, 0.19–1.25) during the overall study period.

The researchers said the ORs recorded in this trial should be viewed with caution because the trial was not adequately powered to show statistically significant differences for efficacy or safety endpoints.

Still, the team said the results suggest edoxaban can provide an alternative to standard therapy.

“At a practical level, our study results show that newly diagnosed, non-anticoagulated AF patients can start edoxaban as early as 2 hours prior to their cardioversion procedure if they have access to [TEE] or 3 weeks prior without,” Dr Goette said.

Warfarin tablets

ROME—The novel oral anticoagulant edoxaban is a feasible treatment option for patients with atrial fibrillation (AF) who need anticoagulation before cardioversion, according to researchers.

Results of the ENSURE-AF trial suggest edoxaban is “an effective and safe alternative” to standard therapy with warfarin and enoxaparin and may allow for prompt cardioversion with transesophageal echocardiography (TEE), said Andreas Goette, MD, of St. Vincenz-Hospital in Paderborn, Germany.

“These results may have important clinical implications for newly diagnosed, non-anticoagulated AF patients undergoing cardioversion,” Dr Goette noted.

“According to the study protocol, a newly diagnosed, non-anticoagulated AF patient was started on edoxaban, and the cardioversion procedure was scheduled as early as 2 hours following the start of treatment, when applying a TEE-guided approach.”

Dr Goette presented results from ENSURE-AF at ESC Congress 2016 (abstract 5715). The data were simultaneously published in The Lancet. The study was supported by Daiichi Sankyo.

This phase 3b study included 2199 patients with documented non-valvular AF who were scheduled for electrical cardioversion after anticoagulation therapy.

Patients were randomized to receive edoxaban (n=1095) or warfarin with enoxaparin bridging (n=1104). Edoxaban was dosed at 60 mg once daily, but the dose was reduced to 30 mg if one or more of the following factors were present: renal impairment, low body weight, or concomitant use of certain P-glycoprotein inhibitors.

Patients were stratified according to the cardioversion approach (TEE or non-TEE), a patient’s prior experience taking anticoagulants at the time of randomization (ie, anticoagulant-experienced or naïve), and edoxaban dose (60 mg or 30 mg). Patients were randomized in a 1:1 ratio to 2 treatment groups within each stratum.

The primary efficacy endpoint was the composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death at day 28.

This endpoint occurred at a comparable rate in both treatment arms—0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (odds ratio [OR]=0.46; 95% CI, 0.12–1.43).

The primary safety endpoint was the composite of major and clinically relevant non-major bleeding events at 30 days.

This endpoint also occurred at a comparable rate in both arms—1.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (OR=1.48; 95% CI, 0.64–3.55).

The result for the net clinical outcome—a composite of stroke, systemic embolic event, myocardial infarction, cardiovascular mortality, and major bleeding—was 0.7% in the edoxaban arm and 1.4% in the enoxaparin/warfarin arm (OR=0.50; 95% CI, 0.19–1.25) during the overall study period.

The researchers said the ORs recorded in this trial should be viewed with caution because the trial was not adequately powered to show statistically significant differences for efficacy or safety endpoints.

Still, the team said the results suggest edoxaban can provide an alternative to standard therapy.

“At a practical level, our study results show that newly diagnosed, non-anticoagulated AF patients can start edoxaban as early as 2 hours prior to their cardioversion procedure if they have access to [TEE] or 3 weeks prior without,” Dr Goette said.

Warfarin tablets

ROME—The novel oral anticoagulant edoxaban is a feasible treatment option for patients with atrial fibrillation (AF) who need anticoagulation before cardioversion, according to researchers.

Results of the ENSURE-AF trial suggest edoxaban is “an effective and safe alternative” to standard therapy with warfarin and enoxaparin and may allow for prompt cardioversion with transesophageal echocardiography (TEE), said Andreas Goette, MD, of St. Vincenz-Hospital in Paderborn, Germany.

“These results may have important clinical implications for newly diagnosed, non-anticoagulated AF patients undergoing cardioversion,” Dr Goette noted.

“According to the study protocol, a newly diagnosed, non-anticoagulated AF patient was started on edoxaban, and the cardioversion procedure was scheduled as early as 2 hours following the start of treatment, when applying a TEE-guided approach.”

Dr Goette presented results from ENSURE-AF at ESC Congress 2016 (abstract 5715). The data were simultaneously published in The Lancet. The study was supported by Daiichi Sankyo.

This phase 3b study included 2199 patients with documented non-valvular AF who were scheduled for electrical cardioversion after anticoagulation therapy.

Patients were randomized to receive edoxaban (n=1095) or warfarin with enoxaparin bridging (n=1104). Edoxaban was dosed at 60 mg once daily, but the dose was reduced to 30 mg if one or more of the following factors were present: renal impairment, low body weight, or concomitant use of certain P-glycoprotein inhibitors.

Patients were stratified according to the cardioversion approach (TEE or non-TEE), a patient’s prior experience taking anticoagulants at the time of randomization (ie, anticoagulant-experienced or naïve), and edoxaban dose (60 mg or 30 mg). Patients were randomized in a 1:1 ratio to 2 treatment groups within each stratum.

The primary efficacy endpoint was the composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death at day 28.

This endpoint occurred at a comparable rate in both treatment arms—0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (odds ratio [OR]=0.46; 95% CI, 0.12–1.43).

The primary safety endpoint was the composite of major and clinically relevant non-major bleeding events at 30 days.

This endpoint also occurred at a comparable rate in both arms—1.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin arm (OR=1.48; 95% CI, 0.64–3.55).

The result for the net clinical outcome—a composite of stroke, systemic embolic event, myocardial infarction, cardiovascular mortality, and major bleeding—was 0.7% in the edoxaban arm and 1.4% in the enoxaparin/warfarin arm (OR=0.50; 95% CI, 0.19–1.25) during the overall study period.

The researchers said the ORs recorded in this trial should be viewed with caution because the trial was not adequately powered to show statistically significant differences for efficacy or safety endpoints.

Still, the team said the results suggest edoxaban can provide an alternative to standard therapy.

“At a practical level, our study results show that newly diagnosed, non-anticoagulated AF patients can start edoxaban as early as 2 hours prior to their cardioversion procedure if they have access to [TEE] or 3 weeks prior without,” Dr Goette said.

Monoclonal antibodies

Photo by Linda Bartlett

The European Commission has granted orphan drug designation to ALXN1007 for the treatment of graft-versus-host disease (GVHD).

ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.

The drug is currently under investigation in a phase 2 trial of patients with newly diagnosed acute GVHD of the lower gastrointestinal tract (GI-GVHD).

ALXN1007 is being developed by Alexion Pharmaceuticals, Inc.

About orphan designation

Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Phase 2 trial of ALXN1007

Results from the phase 2 trial of ALXN1007 in patients with newly diagnosed, acute GI-GVHD were presented at the 21st Congress of the European Hematology Association (abstract LB2269).

The presentation included 15 patients with biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.

Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), or mantle cell lymphoma (n=1).

Most patients received transplants from matched, unrelated donors (n=11), 3 had matched, related donors, and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.

Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 acute GI-GVHD (n=6).

The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.

Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.

The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.

At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.

All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.

Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.

There were 6 deaths, but none were considered treatment-related.

Monoclonal antibodies

Photo by Linda Bartlett

The European Commission has granted orphan drug designation to ALXN1007 for the treatment of graft-versus-host disease (GVHD).

ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.

The drug is currently under investigation in a phase 2 trial of patients with newly diagnosed acute GVHD of the lower gastrointestinal tract (GI-GVHD).

ALXN1007 is being developed by Alexion Pharmaceuticals, Inc.

About orphan designation

Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Phase 2 trial of ALXN1007

Results from the phase 2 trial of ALXN1007 in patients with newly diagnosed, acute GI-GVHD were presented at the 21st Congress of the European Hematology Association (abstract LB2269).

The presentation included 15 patients with biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.

Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), or mantle cell lymphoma (n=1).

Most patients received transplants from matched, unrelated donors (n=11), 3 had matched, related donors, and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.

Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 acute GI-GVHD (n=6).

The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.

Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.

The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.

At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.

All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.

Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.

There were 6 deaths, but none were considered treatment-related.

Monoclonal antibodies

Photo by Linda Bartlett

The European Commission has granted orphan drug designation to ALXN1007 for the treatment of graft-versus-host disease (GVHD).

ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.

The drug is currently under investigation in a phase 2 trial of patients with newly diagnosed acute GVHD of the lower gastrointestinal tract (GI-GVHD).

ALXN1007 is being developed by Alexion Pharmaceuticals, Inc.

About orphan designation

Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Phase 2 trial of ALXN1007

Results from the phase 2 trial of ALXN1007 in patients with newly diagnosed, acute GI-GVHD were presented at the 21st Congress of the European Hematology Association (abstract LB2269).

The presentation included 15 patients with biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.

Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), or mantle cell lymphoma (n=1).

Most patients received transplants from matched, unrelated donors (n=11), 3 had matched, related donors, and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.

Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 acute GI-GVHD (n=6).

The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.

Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.

The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.

At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.

All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.

Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.

There were 6 deaths, but none were considered treatment-related.

Click here to read supplement

Click here to read supplement

Click here to read supplement

Duration of illness, age, and the presence of specific symptoms are key predictors of hospitalization risk due to respiratory infection, according to a study published in The Lancet. These demographic and clinical factors should guide a primary care physician’s decision to prescribe antibiotics.

“More than 80% of all health-service antibiotics [are] prescribed by primary care clinicians,” reported Alastair Hay, MD, of the University of Bristol, England, and his associates.

“Antibiotic prescribing in primary care is increasing and directly affects antimicrobial resistance,” the researchers noted, adding that many primary care clinicians prescribe antibiotics to pediatric patients with respiratory tract infections and/or cough to “mitigate perceived risk of future hospital admission and complications.”

A total of 8,394 pediatric patients who presented with acute cough and one or more other symptoms of respiratory tract infection (such as fever and coryza) were enrolled in the study by primary care physicians at 247 clinical sites in England. All eligible patients were between the ages of 3 months and 16 years; children were excluded if they presented with noninfective exacerbation of asthma, were at high risk of serious infection, or required a throat swab. The study’s primary outcome was hospital admission for any respiratory tract infection within 30 days of enrollment; the data were collected from a review of electronic medical records (Lancet. 2016. Sept 1. doi: 10.1016/S2213-2600[16]30223-5).

©Ryan McVay/ thinkstockphotos.com

The median age of the pediatric cohort was 3 years, 52% were male, and 78% were white. A total of 3,121 patients (37%) were prescribed an antibiotic by their primary care physicians, but only 78 patients (0.9%) were admitted to the hospital, and 27% of discharge diagnoses suggested a possible bacterial cause (lower respiratory tract infection, tonsillitis, and pneumonia).

Multivariate modeling with bootstrap validation demonstrated that duration of illness, age, and the presence or absence of specific respiratory symptoms were the key factors that should be used to identify children at low, normal, and high risk for hospitalization due to respiratory infection. Younger patients with shorter illness durations who presented with wheeze, fever, vomiting, intercostal or subcostal recession, and/or asthma were at higher risk for hospitalization.

“Our data show that 1,846 (33%) of the very-low-risk stratum children received antibiotics. Because these children represent the majority (67%) of all the participants, a 10% overall reduction in antibiotic prescription would be achieved if prescription in this group halved, remained static in the normal risk stratum, and increased to 90% in the high risk stratum, resulting in a similar effect size to other contemporary antimicrobial stewardship interventions,” Dr. Hay and his associates concluded.

This study received funding and sponsorship from the National Institute for Health Research and the University of Bristol. Two investigators reported receiving financial compensation or honoraria from multiple companies including companies with an interest in diagnostic microbiology in respiratory tract infections.

[email protected]

On Twitter @jessnicolecraig

Duration of illness, age, and the presence of specific symptoms are key predictors of hospitalization risk due to respiratory infection, according to a study published in The Lancet. These demographic and clinical factors should guide a primary care physician’s decision to prescribe antibiotics.

“More than 80% of all health-service antibiotics [are] prescribed by primary care clinicians,” reported Alastair Hay, MD, of the University of Bristol, England, and his associates.

“Antibiotic prescribing in primary care is increasing and directly affects antimicrobial resistance,” the researchers noted, adding that many primary care clinicians prescribe antibiotics to pediatric patients with respiratory tract infections and/or cough to “mitigate perceived risk of future hospital admission and complications.”

A total of 8,394 pediatric patients who presented with acute cough and one or more other symptoms of respiratory tract infection (such as fever and coryza) were enrolled in the study by primary care physicians at 247 clinical sites in England. All eligible patients were between the ages of 3 months and 16 years; children were excluded if they presented with noninfective exacerbation of asthma, were at high risk of serious infection, or required a throat swab. The study’s primary outcome was hospital admission for any respiratory tract infection within 30 days of enrollment; the data were collected from a review of electronic medical records (Lancet. 2016. Sept 1. doi: 10.1016/S2213-2600[16]30223-5).

©Ryan McVay/ thinkstockphotos.com

The median age of the pediatric cohort was 3 years, 52% were male, and 78% were white. A total of 3,121 patients (37%) were prescribed an antibiotic by their primary care physicians, but only 78 patients (0.9%) were admitted to the hospital, and 27% of discharge diagnoses suggested a possible bacterial cause (lower respiratory tract infection, tonsillitis, and pneumonia).

Multivariate modeling with bootstrap validation demonstrated that duration of illness, age, and the presence or absence of specific respiratory symptoms were the key factors that should be used to identify children at low, normal, and high risk for hospitalization due to respiratory infection. Younger patients with shorter illness durations who presented with wheeze, fever, vomiting, intercostal or subcostal recession, and/or asthma were at higher risk for hospitalization.

“Our data show that 1,846 (33%) of the very-low-risk stratum children received antibiotics. Because these children represent the majority (67%) of all the participants, a 10% overall reduction in antibiotic prescription would be achieved if prescription in this group halved, remained static in the normal risk stratum, and increased to 90% in the high risk stratum, resulting in a similar effect size to other contemporary antimicrobial stewardship interventions,” Dr. Hay and his associates concluded.

This study received funding and sponsorship from the National Institute for Health Research and the University of Bristol. Two investigators reported receiving financial compensation or honoraria from multiple companies including companies with an interest in diagnostic microbiology in respiratory tract infections.

[email protected]

On Twitter @jessnicolecraig

Duration of illness, age, and the presence of specific symptoms are key predictors of hospitalization risk due to respiratory infection, according to a study published in The Lancet. These demographic and clinical factors should guide a primary care physician’s decision to prescribe antibiotics.

“More than 80% of all health-service antibiotics [are] prescribed by primary care clinicians,” reported Alastair Hay, MD, of the University of Bristol, England, and his associates.

“Antibiotic prescribing in primary care is increasing and directly affects antimicrobial resistance,” the researchers noted, adding that many primary care clinicians prescribe antibiotics to pediatric patients with respiratory tract infections and/or cough to “mitigate perceived risk of future hospital admission and complications.”

A total of 8,394 pediatric patients who presented with acute cough and one or more other symptoms of respiratory tract infection (such as fever and coryza) were enrolled in the study by primary care physicians at 247 clinical sites in England. All eligible patients were between the ages of 3 months and 16 years; children were excluded if they presented with noninfective exacerbation of asthma, were at high risk of serious infection, or required a throat swab. The study’s primary outcome was hospital admission for any respiratory tract infection within 30 days of enrollment; the data were collected from a review of electronic medical records (Lancet. 2016. Sept 1. doi: 10.1016/S2213-2600[16]30223-5).

©Ryan McVay/ thinkstockphotos.com

The median age of the pediatric cohort was 3 years, 52% were male, and 78% were white. A total of 3,121 patients (37%) were prescribed an antibiotic by their primary care physicians, but only 78 patients (0.9%) were admitted to the hospital, and 27% of discharge diagnoses suggested a possible bacterial cause (lower respiratory tract infection, tonsillitis, and pneumonia).

Multivariate modeling with bootstrap validation demonstrated that duration of illness, age, and the presence or absence of specific respiratory symptoms were the key factors that should be used to identify children at low, normal, and high risk for hospitalization due to respiratory infection. Younger patients with shorter illness durations who presented with wheeze, fever, vomiting, intercostal or subcostal recession, and/or asthma were at higher risk for hospitalization.

“Our data show that 1,846 (33%) of the very-low-risk stratum children received antibiotics. Because these children represent the majority (67%) of all the participants, a 10% overall reduction in antibiotic prescription would be achieved if prescription in this group halved, remained static in the normal risk stratum, and increased to 90% in the high risk stratum, resulting in a similar effect size to other contemporary antimicrobial stewardship interventions,” Dr. Hay and his associates concluded.

This study received funding and sponsorship from the National Institute for Health Research and the University of Bristol. Two investigators reported receiving financial compensation or honoraria from multiple companies including companies with an interest in diagnostic microbiology in respiratory tract infections.

[email protected]

On Twitter @jessnicolecraig

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

[email protected]

On Twitter @mitchelzoler

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

[email protected]

On Twitter @alz_gal

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

[email protected]

On Twitter @alz_gal

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

[email protected]

On Twitter @alz_gal

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis.