Jorge Cortes, MD

VIENNA—Administering ponatinib at lower doses can reduce the risk of arterial occlusive events (AOE) without hindering responses in patients with chronic-phase chronic myeloid leukemia (CP-CML), data from the PACE trial suggest.

When earlier results of this phase 2 study showed that ponatinib can cause AOEs, trials of the drug were put on partial clinical hold. Enrollment was stalled temporarily, and investigators began reducing ponatinib doses.

Now, updated data from the PACE trial suggest ponatinib can be administered safely and effectively in certain patients with CP-CML.

At a median follow-up of about 3.5 years, 95% of CP-CML patients who underwent dose reductions maintained a major cytogenetic response (MCyR). And AOEs occurred in 7% of patients who underwent dose reductions, compared to 13% of patients who did not.

“These continued responses . . . in such a heavily pretreated patient population are very encouraging,” said study investigator Jorge E. Cortes, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Careful assessment of the benefit and risk of initiating ponatinib therapy, particularly in patients who may be at increased risk for arterial occlusive events, can help identify patients with refractory, Ph+ leukemias who can benefit most from this treatment.”

Dr Cortes and his colleagues presented data from the PACE trial at the 20th Congress of the European Hematology Association as abstract P234*. The study was sponsored by Ariad Pharmaceuticals, the company developing ponatinib.

Updated results

The trial included patients with resistant or intolerant CML or Philadelphia chromosome-positive acute lymphoblastic leukemia. A total of 449 patients received ponatinib at a starting dose of 45 mg/day.

Ninety-three percent of patients had previously received 2 or more approved tyrosine kinase inhibitors (TKI), and 55% had previously received 3 or more approved TKIs.

Dr Cortes and his colleagues presented data on 270 CP-CML patients. At a median follow-up of 42.3 months (data as of February 2, 2015), 114 patients (42%) continue to receive ponatinib.

Eighteen percent of patients discontinued treatment due to adverse events (AEs), 10% due to disease progression, 3% due to death, and 27% for other reasons.

Fifty-nine percent of CP-CML patients achieved an MCyR at any time during the study, and 83% of responders are estimated to remain in MCyR at 3 years. Thirty-nine percent of patients achieved a major molecular response (MMR).

The estimated progression-free survival at 3 years is 60%, and the estimated overall survival is 81%.

Twenty-three percent of CP-CML patients experienced an AOE designated a serious AE, and 28%  experienced any AOE. The median time to onset for AOEs was 14.1 months (range, 0.3–44.0).

Four percent of CP-CML patients experienced a venous thromboembolism (VTE) that was considered an serious AE, and 5% experienced any VTE.

The most common all-grade, treatment-emergent AEs occurring in at least 40% of CP-CML patients were abdominal pain (46%), rash (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%).

Outcomes after dose reductions

On October 10, 2013, Ariad provided dose-reduction recommendations to investigators for patients remaining on the PACE trial. The following dose reductions were recommended, unless the benefit-risk analysis warranted treatment with a higher dose:

• CP-CML patients who already achieved an MCyR should have their ponatinib dose reduced to 15 mg/day
• CP-CML patients who had not already achieved an MCyR should have their dose reduced to 30 mg/day
• Advanced-phase patients should have their dose reduced to 30 mg/day.

As of February 2015, with 1.3 years (16 months) of follow-up after these recommendations, 95% of CP-CML patients maintained their response, whether or not they underwent prospective dose reductions.

Of the patients who were in MCyR as of October 10, 2013, and had a prospective dose reduction, 95% (61/64) maintained their response at 1.3 years. Of the patients who were in MMR as of October 10, 2013, and had a prospective dose reduction, 94% (44/47) maintained their response at 1.3 years.

Forty-two patients in MCyR did not undergo prospective dose reductions (the majority of which were already at a reduced dose of 30 mg or 15 mg as of October 10, 2013). Of these patients, 93% (n=39) maintained an MCyR after 1.3 more years of ponatinib treatment.

Twenty-four patients in MMR did not undergo prospective dose reductions, and 96% of these patients (n=22) maintained their response at 1.3 years.

Seven percent (5/71) of patients without prior AOEs who underwent dose reductions had a new AOE during the 1.3-year interval after dose reduction.

Thirteen percent (9/67) of patients without prior AOEs who did not undergo dose reductions had a new AOE in the same time interval.

*Information in the abstract differs from that presented at the meeting.

Jorge Cortes, MD

VIENNA—Administering ponatinib at lower doses can reduce the risk of arterial occlusive events (AOE) without hindering responses in patients with chronic-phase chronic myeloid leukemia (CP-CML), data from the PACE trial suggest.

When earlier results of this phase 2 study showed that ponatinib can cause AOEs, trials of the drug were put on partial clinical hold. Enrollment was stalled temporarily, and investigators began reducing ponatinib doses.

Now, updated data from the PACE trial suggest ponatinib can be administered safely and effectively in certain patients with CP-CML.

At a median follow-up of about 3.5 years, 95% of CP-CML patients who underwent dose reductions maintained a major cytogenetic response (MCyR). And AOEs occurred in 7% of patients who underwent dose reductions, compared to 13% of patients who did not.

“These continued responses . . . in such a heavily pretreated patient population are very encouraging,” said study investigator Jorge E. Cortes, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Careful assessment of the benefit and risk of initiating ponatinib therapy, particularly in patients who may be at increased risk for arterial occlusive events, can help identify patients with refractory, Ph+ leukemias who can benefit most from this treatment.”

Dr Cortes and his colleagues presented data from the PACE trial at the 20th Congress of the European Hematology Association as abstract P234*. The study was sponsored by Ariad Pharmaceuticals, the company developing ponatinib.

Updated results

The trial included patients with resistant or intolerant CML or Philadelphia chromosome-positive acute lymphoblastic leukemia. A total of 449 patients received ponatinib at a starting dose of 45 mg/day.

Ninety-three percent of patients had previously received 2 or more approved tyrosine kinase inhibitors (TKI), and 55% had previously received 3 or more approved TKIs.

Dr Cortes and his colleagues presented data on 270 CP-CML patients. At a median follow-up of 42.3 months (data as of February 2, 2015), 114 patients (42%) continue to receive ponatinib.

Eighteen percent of patients discontinued treatment due to adverse events (AEs), 10% due to disease progression, 3% due to death, and 27% for other reasons.

Fifty-nine percent of CP-CML patients achieved an MCyR at any time during the study, and 83% of responders are estimated to remain in MCyR at 3 years. Thirty-nine percent of patients achieved a major molecular response (MMR).

The estimated progression-free survival at 3 years is 60%, and the estimated overall survival is 81%.

Twenty-three percent of CP-CML patients experienced an AOE designated a serious AE, and 28%  experienced any AOE. The median time to onset for AOEs was 14.1 months (range, 0.3–44.0).

Four percent of CP-CML patients experienced a venous thromboembolism (VTE) that was considered an serious AE, and 5% experienced any VTE.

The most common all-grade, treatment-emergent AEs occurring in at least 40% of CP-CML patients were abdominal pain (46%), rash (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%).

Outcomes after dose reductions

On October 10, 2013, Ariad provided dose-reduction recommendations to investigators for patients remaining on the PACE trial. The following dose reductions were recommended, unless the benefit-risk analysis warranted treatment with a higher dose:

• CP-CML patients who already achieved an MCyR should have their ponatinib dose reduced to 15 mg/day
• CP-CML patients who had not already achieved an MCyR should have their dose reduced to 30 mg/day
• Advanced-phase patients should have their dose reduced to 30 mg/day.

As of February 2015, with 1.3 years (16 months) of follow-up after these recommendations, 95% of CP-CML patients maintained their response, whether or not they underwent prospective dose reductions.

Of the patients who were in MCyR as of October 10, 2013, and had a prospective dose reduction, 95% (61/64) maintained their response at 1.3 years. Of the patients who were in MMR as of October 10, 2013, and had a prospective dose reduction, 94% (44/47) maintained their response at 1.3 years.

Forty-two patients in MCyR did not undergo prospective dose reductions (the majority of which were already at a reduced dose of 30 mg or 15 mg as of October 10, 2013). Of these patients, 93% (n=39) maintained an MCyR after 1.3 more years of ponatinib treatment.

Twenty-four patients in MMR did not undergo prospective dose reductions, and 96% of these patients (n=22) maintained their response at 1.3 years.

Seven percent (5/71) of patients without prior AOEs who underwent dose reductions had a new AOE during the 1.3-year interval after dose reduction.

Thirteen percent (9/67) of patients without prior AOEs who did not undergo dose reductions had a new AOE in the same time interval.

*Information in the abstract differs from that presented at the meeting.

Jorge Cortes, MD

VIENNA—Administering ponatinib at lower doses can reduce the risk of arterial occlusive events (AOE) without hindering responses in patients with chronic-phase chronic myeloid leukemia (CP-CML), data from the PACE trial suggest.

When earlier results of this phase 2 study showed that ponatinib can cause AOEs, trials of the drug were put on partial clinical hold. Enrollment was stalled temporarily, and investigators began reducing ponatinib doses.

Now, updated data from the PACE trial suggest ponatinib can be administered safely and effectively in certain patients with CP-CML.

At a median follow-up of about 3.5 years, 95% of CP-CML patients who underwent dose reductions maintained a major cytogenetic response (MCyR). And AOEs occurred in 7% of patients who underwent dose reductions, compared to 13% of patients who did not.

“These continued responses . . . in such a heavily pretreated patient population are very encouraging,” said study investigator Jorge E. Cortes, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Careful assessment of the benefit and risk of initiating ponatinib therapy, particularly in patients who may be at increased risk for arterial occlusive events, can help identify patients with refractory, Ph+ leukemias who can benefit most from this treatment.”

Dr Cortes and his colleagues presented data from the PACE trial at the 20th Congress of the European Hematology Association as abstract P234*. The study was sponsored by Ariad Pharmaceuticals, the company developing ponatinib.

Updated results

The trial included patients with resistant or intolerant CML or Philadelphia chromosome-positive acute lymphoblastic leukemia. A total of 449 patients received ponatinib at a starting dose of 45 mg/day.

Ninety-three percent of patients had previously received 2 or more approved tyrosine kinase inhibitors (TKI), and 55% had previously received 3 or more approved TKIs.

Dr Cortes and his colleagues presented data on 270 CP-CML patients. At a median follow-up of 42.3 months (data as of February 2, 2015), 114 patients (42%) continue to receive ponatinib.

Eighteen percent of patients discontinued treatment due to adverse events (AEs), 10% due to disease progression, 3% due to death, and 27% for other reasons.

Fifty-nine percent of CP-CML patients achieved an MCyR at any time during the study, and 83% of responders are estimated to remain in MCyR at 3 years. Thirty-nine percent of patients achieved a major molecular response (MMR).

The estimated progression-free survival at 3 years is 60%, and the estimated overall survival is 81%.

Twenty-three percent of CP-CML patients experienced an AOE designated a serious AE, and 28%  experienced any AOE. The median time to onset for AOEs was 14.1 months (range, 0.3–44.0).

Four percent of CP-CML patients experienced a venous thromboembolism (VTE) that was considered an serious AE, and 5% experienced any VTE.

The most common all-grade, treatment-emergent AEs occurring in at least 40% of CP-CML patients were abdominal pain (46%), rash (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%).

Outcomes after dose reductions

On October 10, 2013, Ariad provided dose-reduction recommendations to investigators for patients remaining on the PACE trial. The following dose reductions were recommended, unless the benefit-risk analysis warranted treatment with a higher dose:

• CP-CML patients who already achieved an MCyR should have their ponatinib dose reduced to 15 mg/day
• CP-CML patients who had not already achieved an MCyR should have their dose reduced to 30 mg/day
• Advanced-phase patients should have their dose reduced to 30 mg/day.

As of February 2015, with 1.3 years (16 months) of follow-up after these recommendations, 95% of CP-CML patients maintained their response, whether or not they underwent prospective dose reductions.

Of the patients who were in MCyR as of October 10, 2013, and had a prospective dose reduction, 95% (61/64) maintained their response at 1.3 years. Of the patients who were in MMR as of October 10, 2013, and had a prospective dose reduction, 94% (44/47) maintained their response at 1.3 years.

Forty-two patients in MCyR did not undergo prospective dose reductions (the majority of which were already at a reduced dose of 30 mg or 15 mg as of October 10, 2013). Of these patients, 93% (n=39) maintained an MCyR after 1.3 more years of ponatinib treatment.

Twenty-four patients in MMR did not undergo prospective dose reductions, and 96% of these patients (n=22) maintained their response at 1.3 years.

Seven percent (5/71) of patients without prior AOEs who underwent dose reductions had a new AOE during the 1.3-year interval after dose reduction.

Thirteen percent (9/67) of patients without prior AOEs who did not undergo dose reductions had a new AOE in the same time interval.

*Information in the abstract differs from that presented at the meeting.

Blood smear showing PV

Image courtesy of AFIP

VIENNA—Updated results from the phase 3 RESPONSE trial suggest the JAK1/2 inhibitor ruxolitinib can provide long-term disease control in patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea.

At 18 months of follow-up, 80% of patients had achieved a durable response to ruxolitinib, sustaining hematocrit levels below 45% without the use of phlebotomy and experiencing reductions in spleen size.

In addition, 83% of patients were still receiving ruxolitinib at last follow-up.

“Polycythemia vera can lead to serious complications if inadequately controlled, and these data demonstrate the ability of [ruxolitinib] to provide a durable and comprehensive clinical benefit in this patient population,” said Jean-Jacques Kiladjian, MD, PhD, of Hôpital Saint-Louis et Université Paris Diderot in France.

Dr Kiladjian presented these results at the 20th Congress of the European Hematology Association (abstract S447). The RESPONSE trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study included 222 patients with PV whose were resistant to or could not tolerate hydroxyurea. They were randomized 1:1 to receive either ruxolitinib (at a starting dose of 10 mg twice daily) or best available therapy (BAT), which was defined as investigator-selected monotherapy or observation only. The ruxolitinib dose was adjusted as needed throughout the trial.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from week 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

Patients were deemed eligible for phlebotomy if they had hematocrit that was greater than 45% and had increased 3 or more percentage points from the time they entered the trial or if they had hematocrit greater than 48%.

The researchers performed a second, preplanned analysis at 80 weeks (18 months), evaluating the durability of primary response, hematocrit control, spleen size reduction, complete hematologic remission, and safety. The team also conducted a separate analysis evaluating hematologic parameters.

Results at 32 and 80 weeks

Twenty-one percent of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved the primary endpoint (P<0.0001). All but 1 of the responders in the ruxolitinib arm maintained this response at 80 weeks.

Sixty percent of patients in the ruxolitinib arm and 20% in the BAT arm achieved hematocrit control without phlebotomy through week 32. Patients in the ruxolitinib arm had an 89% probability of maintaining this response for 80 weeks from the time of initial response. Of the 98 patients on ruxolitinib at week 32, 90% did not have a phlebotomy between weeks 32 and 80.

At week 32, 38% of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved a 35% or greater reduction in spleen volume. All of the ruxolitinib-treated patients maintained this response at 80 weeks.

At week 32, 24% of patients in the ruxolitinib arm had a complete hematologic remission, as did 9% of patients in the BAT arm. Patients in the ruxolitinib arm had a 69% probability of maintaining this response for 80 weeks.

A separate analysis of the data at 18 months demonstrated that ruxolitinib treatment also led to sustained control of white blood cell and platelet levels, with the largest reductions occurring in patients who had the most elevated values at baseline.

At week 80, 83% of patients in the ruxolitinib arm remained on treatment (median exposure of 111 weeks), but none of the patients in the BAT arm were still receiving their assigned therapy.

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued treatment due to adverse events.

“There is currently a significant unmet need for patients with polycythemia vera who are unable to tolerate or control their disease on other treatments,” Dr Kiladjian said. “For these patients, [ruxolitinib] represents a valuable new option, as confirmed by results from the long-term, phase 3 study.”

Blood smear showing PV

Image courtesy of AFIP

VIENNA—Updated results from the phase 3 RESPONSE trial suggest the JAK1/2 inhibitor ruxolitinib can provide long-term disease control in patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea.

At 18 months of follow-up, 80% of patients had achieved a durable response to ruxolitinib, sustaining hematocrit levels below 45% without the use of phlebotomy and experiencing reductions in spleen size.

In addition, 83% of patients were still receiving ruxolitinib at last follow-up.

“Polycythemia vera can lead to serious complications if inadequately controlled, and these data demonstrate the ability of [ruxolitinib] to provide a durable and comprehensive clinical benefit in this patient population,” said Jean-Jacques Kiladjian, MD, PhD, of Hôpital Saint-Louis et Université Paris Diderot in France.

Dr Kiladjian presented these results at the 20th Congress of the European Hematology Association (abstract S447). The RESPONSE trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study included 222 patients with PV whose were resistant to or could not tolerate hydroxyurea. They were randomized 1:1 to receive either ruxolitinib (at a starting dose of 10 mg twice daily) or best available therapy (BAT), which was defined as investigator-selected monotherapy or observation only. The ruxolitinib dose was adjusted as needed throughout the trial.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from week 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

Patients were deemed eligible for phlebotomy if they had hematocrit that was greater than 45% and had increased 3 or more percentage points from the time they entered the trial or if they had hematocrit greater than 48%.

The researchers performed a second, preplanned analysis at 80 weeks (18 months), evaluating the durability of primary response, hematocrit control, spleen size reduction, complete hematologic remission, and safety. The team also conducted a separate analysis evaluating hematologic parameters.

Results at 32 and 80 weeks

Twenty-one percent of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved the primary endpoint (P<0.0001). All but 1 of the responders in the ruxolitinib arm maintained this response at 80 weeks.

Sixty percent of patients in the ruxolitinib arm and 20% in the BAT arm achieved hematocrit control without phlebotomy through week 32. Patients in the ruxolitinib arm had an 89% probability of maintaining this response for 80 weeks from the time of initial response. Of the 98 patients on ruxolitinib at week 32, 90% did not have a phlebotomy between weeks 32 and 80.

At week 32, 38% of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved a 35% or greater reduction in spleen volume. All of the ruxolitinib-treated patients maintained this response at 80 weeks.

At week 32, 24% of patients in the ruxolitinib arm had a complete hematologic remission, as did 9% of patients in the BAT arm. Patients in the ruxolitinib arm had a 69% probability of maintaining this response for 80 weeks.

A separate analysis of the data at 18 months demonstrated that ruxolitinib treatment also led to sustained control of white blood cell and platelet levels, with the largest reductions occurring in patients who had the most elevated values at baseline.

At week 80, 83% of patients in the ruxolitinib arm remained on treatment (median exposure of 111 weeks), but none of the patients in the BAT arm were still receiving their assigned therapy.

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued treatment due to adverse events.

“There is currently a significant unmet need for patients with polycythemia vera who are unable to tolerate or control their disease on other treatments,” Dr Kiladjian said. “For these patients, [ruxolitinib] represents a valuable new option, as confirmed by results from the long-term, phase 3 study.”

Blood smear showing PV

Image courtesy of AFIP

VIENNA—Updated results from the phase 3 RESPONSE trial suggest the JAK1/2 inhibitor ruxolitinib can provide long-term disease control in patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea.

At 18 months of follow-up, 80% of patients had achieved a durable response to ruxolitinib, sustaining hematocrit levels below 45% without the use of phlebotomy and experiencing reductions in spleen size.

In addition, 83% of patients were still receiving ruxolitinib at last follow-up.

“Polycythemia vera can lead to serious complications if inadequately controlled, and these data demonstrate the ability of [ruxolitinib] to provide a durable and comprehensive clinical benefit in this patient population,” said Jean-Jacques Kiladjian, MD, PhD, of Hôpital Saint-Louis et Université Paris Diderot in France.

Dr Kiladjian presented these results at the 20th Congress of the European Hematology Association (abstract S447). The RESPONSE trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study included 222 patients with PV whose were resistant to or could not tolerate hydroxyurea. They were randomized 1:1 to receive either ruxolitinib (at a starting dose of 10 mg twice daily) or best available therapy (BAT), which was defined as investigator-selected monotherapy or observation only. The ruxolitinib dose was adjusted as needed throughout the trial.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from week 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

Patients were deemed eligible for phlebotomy if they had hematocrit that was greater than 45% and had increased 3 or more percentage points from the time they entered the trial or if they had hematocrit greater than 48%.

The researchers performed a second, preplanned analysis at 80 weeks (18 months), evaluating the durability of primary response, hematocrit control, spleen size reduction, complete hematologic remission, and safety. The team also conducted a separate analysis evaluating hematologic parameters.

Results at 32 and 80 weeks

Twenty-one percent of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved the primary endpoint (P<0.0001). All but 1 of the responders in the ruxolitinib arm maintained this response at 80 weeks.

Sixty percent of patients in the ruxolitinib arm and 20% in the BAT arm achieved hematocrit control without phlebotomy through week 32. Patients in the ruxolitinib arm had an 89% probability of maintaining this response for 80 weeks from the time of initial response. Of the 98 patients on ruxolitinib at week 32, 90% did not have a phlebotomy between weeks 32 and 80.

At week 32, 38% of patients in the ruxolitinib arm and 1% of patients in the BAT arm achieved a 35% or greater reduction in spleen volume. All of the ruxolitinib-treated patients maintained this response at 80 weeks.

At week 32, 24% of patients in the ruxolitinib arm had a complete hematologic remission, as did 9% of patients in the BAT arm. Patients in the ruxolitinib arm had a 69% probability of maintaining this response for 80 weeks.

A separate analysis of the data at 18 months demonstrated that ruxolitinib treatment also led to sustained control of white blood cell and platelet levels, with the largest reductions occurring in patients who had the most elevated values at baseline.

At week 80, 83% of patients in the ruxolitinib arm remained on treatment (median exposure of 111 weeks), but none of the patients in the BAT arm were still receiving their assigned therapy.

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued treatment due to adverse events.

“There is currently a significant unmet need for patients with polycythemia vera who are unable to tolerate or control their disease on other treatments,” Dr Kiladjian said. “For these patients, [ruxolitinib] represents a valuable new option, as confirmed by results from the long-term, phase 3 study.”

Cardiac amyloidosis

VIENNA—A monoclonal antibody (mAb) can produce responses in patients with light chain (AL) amyloidosis and persistent organ dysfunction, according to research presented at the 20th Congress of the European Hematology Association.

In an ongoing phase 1/2 trial, the mAb, known as NEOD001, produced a cardiac response in 57% of evaluable patients and a renal response in 60% of evaluable patients.

Michaela Liedtke, MD, of the Stanford University School of Medicine in California, presented these results as abstract S104*. The research was sponsored by Prothena Therapeutics Ltd., the company developing NEOD001.

Dr Liedtke presented results of an interim analysis as of February 28, 2015. The analysis included 27 patients with AL amyloidosis who had received 1 or more anti-plasma-cell systemic therapies, had a partial response or better, and did not require additional chemotherapy. The patients also had persistent organ dysfunction.

Patients received a dose of NEOD001 every 28 days, in 1 of 7 dosing cohorts (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 16 mg/kg, and 24 mg/kg). They received a total of 327 infusions, with an average treatment duration of 12 months.

The patients’ median age was 60 (range, 38-80), and they had received a median of 2 prior treatments (range, 1-7). A third of patients each had 1 organ system involved (n=9), 2 organ systems involved (n=9), or 3 or more organ systems involved (n=9).

Safety data

The most frequently reported treatment-emergent adverse events (occurring in more than 10% of subjects) were fatigue (37%), upper respiratory tract infection (26%), cough (19%), dyspnea (19%), headache (15%), anemia (15%), increased blood creatinine (15%), peripheral edema (15%), edema (11%), diarrhea (11%), nausea (11%), and hyponatremia (11%).

There were no reports of hypersensitivity reactions to NEOD001 or drug-related serious adverse events, and no anti-NEOD001 antibodies were detected. There were no dose-limiting toxicities, and none of the patients discontinued treatment due to drug-related adverse events.

All patients remaining in the study were escalated to a dose of 24 mg/kg as of December 2, 2014.

Renal and cardiac responses

In a best-response analysis, 60% (9/15) of renal-evaluable patients demonstrated a renal response to NEOD001, defined as a 30% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening. The other 40% of patients (n=6) had stable disease.

In another best-response analysis, 57% (8/14) of cardiac-evaluable patients had a cardiac response to NEOD001, defined as more than 30% and 300 pg/mL decrease in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). The other 43% of patients (n=6) had stable disease.

Longer treatment with NEOD001 was significantly associated with NT-proBNP decline (P<0.0001).

“[M]onthly infusions of NEOD001 correlate significantly with decreases in both cardiac and renal biomarkers over time,” Dr Liedtke said. “Decreases in cardiac biomarkers predict increased survival, and decreases in renal biomarkers predict delayed time to kidney failure.”

*Information in the abstract differs from that presented at the meeting.

Cardiac amyloidosis

VIENNA—A monoclonal antibody (mAb) can produce responses in patients with light chain (AL) amyloidosis and persistent organ dysfunction, according to research presented at the 20th Congress of the European Hematology Association.

In an ongoing phase 1/2 trial, the mAb, known as NEOD001, produced a cardiac response in 57% of evaluable patients and a renal response in 60% of evaluable patients.

Michaela Liedtke, MD, of the Stanford University School of Medicine in California, presented these results as abstract S104*. The research was sponsored by Prothena Therapeutics Ltd., the company developing NEOD001.

Dr Liedtke presented results of an interim analysis as of February 28, 2015. The analysis included 27 patients with AL amyloidosis who had received 1 or more anti-plasma-cell systemic therapies, had a partial response or better, and did not require additional chemotherapy. The patients also had persistent organ dysfunction.

Patients received a dose of NEOD001 every 28 days, in 1 of 7 dosing cohorts (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 16 mg/kg, and 24 mg/kg). They received a total of 327 infusions, with an average treatment duration of 12 months.

The patients’ median age was 60 (range, 38-80), and they had received a median of 2 prior treatments (range, 1-7). A third of patients each had 1 organ system involved (n=9), 2 organ systems involved (n=9), or 3 or more organ systems involved (n=9).

Safety data

The most frequently reported treatment-emergent adverse events (occurring in more than 10% of subjects) were fatigue (37%), upper respiratory tract infection (26%), cough (19%), dyspnea (19%), headache (15%), anemia (15%), increased blood creatinine (15%), peripheral edema (15%), edema (11%), diarrhea (11%), nausea (11%), and hyponatremia (11%).

There were no reports of hypersensitivity reactions to NEOD001 or drug-related serious adverse events, and no anti-NEOD001 antibodies were detected. There were no dose-limiting toxicities, and none of the patients discontinued treatment due to drug-related adverse events.

All patients remaining in the study were escalated to a dose of 24 mg/kg as of December 2, 2014.

Renal and cardiac responses

In a best-response analysis, 60% (9/15) of renal-evaluable patients demonstrated a renal response to NEOD001, defined as a 30% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening. The other 40% of patients (n=6) had stable disease.

In another best-response analysis, 57% (8/14) of cardiac-evaluable patients had a cardiac response to NEOD001, defined as more than 30% and 300 pg/mL decrease in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). The other 43% of patients (n=6) had stable disease.

Longer treatment with NEOD001 was significantly associated with NT-proBNP decline (P<0.0001).

“[M]onthly infusions of NEOD001 correlate significantly with decreases in both cardiac and renal biomarkers over time,” Dr Liedtke said. “Decreases in cardiac biomarkers predict increased survival, and decreases in renal biomarkers predict delayed time to kidney failure.”

*Information in the abstract differs from that presented at the meeting.

Cardiac amyloidosis

VIENNA—A monoclonal antibody (mAb) can produce responses in patients with light chain (AL) amyloidosis and persistent organ dysfunction, according to research presented at the 20th Congress of the European Hematology Association.

In an ongoing phase 1/2 trial, the mAb, known as NEOD001, produced a cardiac response in 57% of evaluable patients and a renal response in 60% of evaluable patients.

Michaela Liedtke, MD, of the Stanford University School of Medicine in California, presented these results as abstract S104*. The research was sponsored by Prothena Therapeutics Ltd., the company developing NEOD001.

Dr Liedtke presented results of an interim analysis as of February 28, 2015. The analysis included 27 patients with AL amyloidosis who had received 1 or more anti-plasma-cell systemic therapies, had a partial response or better, and did not require additional chemotherapy. The patients also had persistent organ dysfunction.

Patients received a dose of NEOD001 every 28 days, in 1 of 7 dosing cohorts (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 16 mg/kg, and 24 mg/kg). They received a total of 327 infusions, with an average treatment duration of 12 months.

The patients’ median age was 60 (range, 38-80), and they had received a median of 2 prior treatments (range, 1-7). A third of patients each had 1 organ system involved (n=9), 2 organ systems involved (n=9), or 3 or more organ systems involved (n=9).

Safety data

The most frequently reported treatment-emergent adverse events (occurring in more than 10% of subjects) were fatigue (37%), upper respiratory tract infection (26%), cough (19%), dyspnea (19%), headache (15%), anemia (15%), increased blood creatinine (15%), peripheral edema (15%), edema (11%), diarrhea (11%), nausea (11%), and hyponatremia (11%).

There were no reports of hypersensitivity reactions to NEOD001 or drug-related serious adverse events, and no anti-NEOD001 antibodies were detected. There were no dose-limiting toxicities, and none of the patients discontinued treatment due to drug-related adverse events.

All patients remaining in the study were escalated to a dose of 24 mg/kg as of December 2, 2014.

Renal and cardiac responses

In a best-response analysis, 60% (9/15) of renal-evaluable patients demonstrated a renal response to NEOD001, defined as a 30% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening. The other 40% of patients (n=6) had stable disease.

In another best-response analysis, 57% (8/14) of cardiac-evaluable patients had a cardiac response to NEOD001, defined as more than 30% and 300 pg/mL decrease in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). The other 43% of patients (n=6) had stable disease.

Longer treatment with NEOD001 was significantly associated with NT-proBNP decline (P<0.0001).

“[M]onthly infusions of NEOD001 correlate significantly with decreases in both cardiac and renal biomarkers over time,” Dr Liedtke said. “Decreases in cardiac biomarkers predict increased survival, and decreases in renal biomarkers predict delayed time to kidney failure.”

*Information in the abstract differs from that presented at the meeting.

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

There is a persistent, unresolved debate regarding the perioperative management of clopidogrel (Plavix) among patients undergoing carotid endarterectomy (CEA).

”Surgeons often have to decide whether or not to continue antiplatelet drugs at the time of carotid endarterectomy.  Most feel comfortable continuing aspirin but there is uncertainty about how to manage patients on clopidogrel as well.

“Our goal was to try and address this frequently encountered problem in a way that helps surgeons decide how to manage these medications,” according to Dr. Douglas W. Jones of New York Presbyterian Hospital Weill-Cornell Medical Center, New York, and Dr. David H. Stone of Dartmouth-Hitchcock Medical Center.

Dr. Jones will reported on their study examining the impact of dual antiplatelet therapy (clopidogrel plus aspirin) on perioperative CEA outcomes in more than 34,000 patients treated over the period 2003 to 2014 at the 2015 Vascular Annual Meeting.

Among the 34,477 patients undergoing CEA in the Vascular Quality Initiative database, 63% (21,624) were on aspirin and 20% (7,059) were on clopidogrel and aspirin.  

In order to isolate the effect of clopidogrel, patients on clopidogrel and aspirin (dual therapy) were compared to patients taking aspirin alone.

Multivariate analyses and propensity score matching were employed to control for subgroup heterogeneity. The outcomes of the study included reoperation for bleeding (RTOR), neurologic events (transient ischemic attack or stroke), stroke, death, myocardial infarction (MI), and stroke/death.

Dr. Jones and his colleagues found that those patients who were on dual therapy were significantly more likely to have multiple comorbidities, including coronary artery disease, congestive heart failure, COPD, as well as diabetes.

However, after controlling for these differences, multivariate analysis showed that dual therapy was independently and significantly associated with increased RTOR (OR 1.74), but was also significantly protective against neurologic events (OR 0.61), any stroke (OR 0.62), and stroke/death (0.65).

Further analysis with propensity score matching yielded 2 well-matched groups of 4,548 patients.

Propensity score matching confirmed that patients on dual therapy were more likely to return to the OR for bleeding but were less likely to suffer neurologic events, stroke, or stroke/death.

“Our study shows that continuation of clopidogrel at the time of CEA was associated with a near 40% reduction in neurologic events, but it exposed patients to an increased bleeding risk,” said Dr. Jones.

“Accordingly, surgeons must judiciously assess the perioperative risk/benefit trade-off at the time of CEA for patients on dual antiplatelet therapy,” he concluded.

There is a persistent, unresolved debate regarding the perioperative management of clopidogrel (Plavix) among patients undergoing carotid endarterectomy (CEA).

”Surgeons often have to decide whether or not to continue antiplatelet drugs at the time of carotid endarterectomy.  Most feel comfortable continuing aspirin but there is uncertainty about how to manage patients on clopidogrel as well.

“Our goal was to try and address this frequently encountered problem in a way that helps surgeons decide how to manage these medications,” according to Dr. Douglas W. Jones of New York Presbyterian Hospital Weill-Cornell Medical Center, New York, and Dr. David H. Stone of Dartmouth-Hitchcock Medical Center.

Dr. Jones will reported on their study examining the impact of dual antiplatelet therapy (clopidogrel plus aspirin) on perioperative CEA outcomes in more than 34,000 patients treated over the period 2003 to 2014 at the 2015 Vascular Annual Meeting.

Among the 34,477 patients undergoing CEA in the Vascular Quality Initiative database, 63% (21,624) were on aspirin and 20% (7,059) were on clopidogrel and aspirin.  

In order to isolate the effect of clopidogrel, patients on clopidogrel and aspirin (dual therapy) were compared to patients taking aspirin alone.

Multivariate analyses and propensity score matching were employed to control for subgroup heterogeneity. The outcomes of the study included reoperation for bleeding (RTOR), neurologic events (transient ischemic attack or stroke), stroke, death, myocardial infarction (MI), and stroke/death.

Dr. Jones and his colleagues found that those patients who were on dual therapy were significantly more likely to have multiple comorbidities, including coronary artery disease, congestive heart failure, COPD, as well as diabetes.

However, after controlling for these differences, multivariate analysis showed that dual therapy was independently and significantly associated with increased RTOR (OR 1.74), but was also significantly protective against neurologic events (OR 0.61), any stroke (OR 0.62), and stroke/death (0.65).

Further analysis with propensity score matching yielded 2 well-matched groups of 4,548 patients.

Propensity score matching confirmed that patients on dual therapy were more likely to return to the OR for bleeding but were less likely to suffer neurologic events, stroke, or stroke/death.

“Our study shows that continuation of clopidogrel at the time of CEA was associated with a near 40% reduction in neurologic events, but it exposed patients to an increased bleeding risk,” said Dr. Jones.

“Accordingly, surgeons must judiciously assess the perioperative risk/benefit trade-off at the time of CEA for patients on dual antiplatelet therapy,” he concluded.

There is a persistent, unresolved debate regarding the perioperative management of clopidogrel (Plavix) among patients undergoing carotid endarterectomy (CEA).

”Surgeons often have to decide whether or not to continue antiplatelet drugs at the time of carotid endarterectomy.  Most feel comfortable continuing aspirin but there is uncertainty about how to manage patients on clopidogrel as well.

“Our goal was to try and address this frequently encountered problem in a way that helps surgeons decide how to manage these medications,” according to Dr. Douglas W. Jones of New York Presbyterian Hospital Weill-Cornell Medical Center, New York, and Dr. David H. Stone of Dartmouth-Hitchcock Medical Center.

Dr. Jones will reported on their study examining the impact of dual antiplatelet therapy (clopidogrel plus aspirin) on perioperative CEA outcomes in more than 34,000 patients treated over the period 2003 to 2014 at the 2015 Vascular Annual Meeting.

Among the 34,477 patients undergoing CEA in the Vascular Quality Initiative database, 63% (21,624) were on aspirin and 20% (7,059) were on clopidogrel and aspirin.  

In order to isolate the effect of clopidogrel, patients on clopidogrel and aspirin (dual therapy) were compared to patients taking aspirin alone.

Multivariate analyses and propensity score matching were employed to control for subgroup heterogeneity. The outcomes of the study included reoperation for bleeding (RTOR), neurologic events (transient ischemic attack or stroke), stroke, death, myocardial infarction (MI), and stroke/death.

Dr. Jones and his colleagues found that those patients who were on dual therapy were significantly more likely to have multiple comorbidities, including coronary artery disease, congestive heart failure, COPD, as well as diabetes.

However, after controlling for these differences, multivariate analysis showed that dual therapy was independently and significantly associated with increased RTOR (OR 1.74), but was also significantly protective against neurologic events (OR 0.61), any stroke (OR 0.62), and stroke/death (0.65).

Further analysis with propensity score matching yielded 2 well-matched groups of 4,548 patients.

Propensity score matching confirmed that patients on dual therapy were more likely to return to the OR for bleeding but were less likely to suffer neurologic events, stroke, or stroke/death.

“Our study shows that continuation of clopidogrel at the time of CEA was associated with a near 40% reduction in neurologic events, but it exposed patients to an increased bleeding risk,” said Dr. Jones.

“Accordingly, surgeons must judiciously assess the perioperative risk/benefit trade-off at the time of CEA for patients on dual antiplatelet therapy,” he concluded.

Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?

The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.

The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.

So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.

Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.

As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.

Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.

Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.

Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?

The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.

The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.

So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.

Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.

As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.

Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.

Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.

Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?

The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.

The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.

So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).

The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.

Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.

As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.

Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.

Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.

Our local daily paper, like most other print newspapers, is on its last legs. But I read it faithfully for the obituaries, and to see how my former patients are doing on their school sports teams. Of course, there is always the smattering of motor vehicle accident reports to keep me reading.

One doesn’t have to be an insurance adjuster or an actuary to realize that motor vehicle accident fatalities cluster into two groups: teenagers and older folks (70 plus). One group falls victim to inexperience and a delusional sense of immortality. Those in the other group are losing their ability to sense their environment and respond with sufficient speed. One group makes poor decisions. The other makes them too slowly.

Because my mother died in her early 60s and my father never had a driver’s license, I never faced the difficult task of telling my aging parents that they were too old to drive. But I have heard from some of my friends of how difficult it was to ask Mom and Dad to give up their car keys.

The American Medical Association announced recently that they have to decided to take on a similar challenge by agreeing to “spearhead an effort to create competency guidelines for assessing whether older physicians remain able to provide safe and effective care for patients” (“Aging MDs Prompt Call for Competency Tests at AMA Meeting,” Associated Press, June 8, 2015). Prompted by the reality that one in four physicians in this country is over the age of 65 years, the AMA is beginning to talk about the issue and formulate plans to convene a variety of councils and work groups.

I’m sure there are some older physicians whose clinical skills have eroded with age to a point that they pose a significant threat to the safety of their patients, but I don’t think the situation warrants a full-court press by the AMA or anyone else for that matter.

First, I suspect that most physicians who continue to practice after they turn 70 years are not doing so because they need the money. That might be true 10-15 years from now when today’s young physicians are facing retirement while they are still recovering from the monstrous educational debts they incurred in their 20s. At present, though, I suspect that most physicians continue to practice because they enjoy what they do. I have to believe that a physician whose primary motivation is the joy of seeing patients is, in general, going to be doing a good job of it – and his or her patients probably know it and appreciate it.

Second, we already have in place (or should have) systems for identifying and dealing with physicians who are practicing substandard care for variety of reasons, such as substance abuse, financial malfeasance, inadequate training, or outright incompetence. Do we really need another layer of screening for older physicians? It feels like just another example of profiling. For example, does the Transportation Security Administration need to strip search every male with a dark complexion named Hassan?

The problem is that in many situations our safety nets for identifying and addressing incompetent physicians have too many holes in them. One of the reasons for this inadequacy is the unofficial code of silence that physicians have followed for years. Unless a fellow physician’s behavior is three orders of magnitude beyond the pale, many of us feel uncomfortable about approaching him or her or even lodging an anonymous report to the state board of licensure.

Of course, as physicians age some will lose critical clinical skills. On the other hand, with age many older physicians have gained perspectives on health, life, and death that their younger colleagues need to hear. We don’t need to single out older physicians for closer scrutiny. We simply have to improve our current surveillance systems and attitudes for physicians of all ages. If anyone wants to look more closely at how older physicians practice, the first question to ask should not be “What are they doing wrong?” but “What are these folks doing right that allows them to continue to enjoy practicing medicine at age 75?”

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

Our local daily paper, like most other print newspapers, is on its last legs. But I read it faithfully for the obituaries, and to see how my former patients are doing on their school sports teams. Of course, there is always the smattering of motor vehicle accident reports to keep me reading.

One doesn’t have to be an insurance adjuster or an actuary to realize that motor vehicle accident fatalities cluster into two groups: teenagers and older folks (70 plus). One group falls victim to inexperience and a delusional sense of immortality. Those in the other group are losing their ability to sense their environment and respond with sufficient speed. One group makes poor decisions. The other makes them too slowly.

Because my mother died in her early 60s and my father never had a driver’s license, I never faced the difficult task of telling my aging parents that they were too old to drive. But I have heard from some of my friends of how difficult it was to ask Mom and Dad to give up their car keys.

The American Medical Association announced recently that they have to decided to take on a similar challenge by agreeing to “spearhead an effort to create competency guidelines for assessing whether older physicians remain able to provide safe and effective care for patients” (“Aging MDs Prompt Call for Competency Tests at AMA Meeting,” Associated Press, June 8, 2015). Prompted by the reality that one in four physicians in this country is over the age of 65 years, the AMA is beginning to talk about the issue and formulate plans to convene a variety of councils and work groups.

I’m sure there are some older physicians whose clinical skills have eroded with age to a point that they pose a significant threat to the safety of their patients, but I don’t think the situation warrants a full-court press by the AMA or anyone else for that matter.

First, I suspect that most physicians who continue to practice after they turn 70 years are not doing so because they need the money. That might be true 10-15 years from now when today’s young physicians are facing retirement while they are still recovering from the monstrous educational debts they incurred in their 20s. At present, though, I suspect that most physicians continue to practice because they enjoy what they do. I have to believe that a physician whose primary motivation is the joy of seeing patients is, in general, going to be doing a good job of it – and his or her patients probably know it and appreciate it.

Second, we already have in place (or should have) systems for identifying and dealing with physicians who are practicing substandard care for variety of reasons, such as substance abuse, financial malfeasance, inadequate training, or outright incompetence. Do we really need another layer of screening for older physicians? It feels like just another example of profiling. For example, does the Transportation Security Administration need to strip search every male with a dark complexion named Hassan?

The problem is that in many situations our safety nets for identifying and addressing incompetent physicians have too many holes in them. One of the reasons for this inadequacy is the unofficial code of silence that physicians have followed for years. Unless a fellow physician’s behavior is three orders of magnitude beyond the pale, many of us feel uncomfortable about approaching him or her or even lodging an anonymous report to the state board of licensure.

Of course, as physicians age some will lose critical clinical skills. On the other hand, with age many older physicians have gained perspectives on health, life, and death that their younger colleagues need to hear. We don’t need to single out older physicians for closer scrutiny. We simply have to improve our current surveillance systems and attitudes for physicians of all ages. If anyone wants to look more closely at how older physicians practice, the first question to ask should not be “What are they doing wrong?” but “What are these folks doing right that allows them to continue to enjoy practicing medicine at age 75?”

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

Our local daily paper, like most other print newspapers, is on its last legs. But I read it faithfully for the obituaries, and to see how my former patients are doing on their school sports teams. Of course, there is always the smattering of motor vehicle accident reports to keep me reading.

One doesn’t have to be an insurance adjuster or an actuary to realize that motor vehicle accident fatalities cluster into two groups: teenagers and older folks (70 plus). One group falls victim to inexperience and a delusional sense of immortality. Those in the other group are losing their ability to sense their environment and respond with sufficient speed. One group makes poor decisions. The other makes them too slowly.

Because my mother died in her early 60s and my father never had a driver’s license, I never faced the difficult task of telling my aging parents that they were too old to drive. But I have heard from some of my friends of how difficult it was to ask Mom and Dad to give up their car keys.

The American Medical Association announced recently that they have to decided to take on a similar challenge by agreeing to “spearhead an effort to create competency guidelines for assessing whether older physicians remain able to provide safe and effective care for patients” (“Aging MDs Prompt Call for Competency Tests at AMA Meeting,” Associated Press, June 8, 2015). Prompted by the reality that one in four physicians in this country is over the age of 65 years, the AMA is beginning to talk about the issue and formulate plans to convene a variety of councils and work groups.

I’m sure there are some older physicians whose clinical skills have eroded with age to a point that they pose a significant threat to the safety of their patients, but I don’t think the situation warrants a full-court press by the AMA or anyone else for that matter.

First, I suspect that most physicians who continue to practice after they turn 70 years are not doing so because they need the money. That might be true 10-15 years from now when today’s young physicians are facing retirement while they are still recovering from the monstrous educational debts they incurred in their 20s. At present, though, I suspect that most physicians continue to practice because they enjoy what they do. I have to believe that a physician whose primary motivation is the joy of seeing patients is, in general, going to be doing a good job of it – and his or her patients probably know it and appreciate it.

Second, we already have in place (or should have) systems for identifying and dealing with physicians who are practicing substandard care for variety of reasons, such as substance abuse, financial malfeasance, inadequate training, or outright incompetence. Do we really need another layer of screening for older physicians? It feels like just another example of profiling. For example, does the Transportation Security Administration need to strip search every male with a dark complexion named Hassan?

The problem is that in many situations our safety nets for identifying and addressing incompetent physicians have too many holes in them. One of the reasons for this inadequacy is the unofficial code of silence that physicians have followed for years. Unless a fellow physician’s behavior is three orders of magnitude beyond the pale, many of us feel uncomfortable about approaching him or her or even lodging an anonymous report to the state board of licensure.

Of course, as physicians age some will lose critical clinical skills. On the other hand, with age many older physicians have gained perspectives on health, life, and death that their younger colleagues need to hear. We don’t need to single out older physicians for closer scrutiny. We simply have to improve our current surveillance systems and attitudes for physicians of all ages. If anyone wants to look more closely at how older physicians practice, the first question to ask should not be “What are they doing wrong?” but “What are these folks doing right that allows them to continue to enjoy practicing medicine at age 75?”

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

The Suicide Prevention Resource Center (SPRC) has released Caring for Adult Patients with Suicide Risk: A Consensus Guide for Emergency Departments.

The Suicide Prevention Resource Center (SPRC) is the nation’s only federally-supported resource center devoted to advancing the National Strategy for Suicide Prevention. The guide includes evidence-based practices in decision support, initial interventions, and discharge planning for adults who have been identified as having some risk of suicide.

“Emergency departments are prime sites for suicide prevention activities in the U.S., but until now clinicians have not had tools to help them steer patients toward treatment options that best meet their health and safety needs,”  Pamela S. Hyde, Administrator of the Substance Abuse and Mental Health Services Administration (SAMHSA) said in a press release.

Funded by SAMHSA, the guide was based on a literature review and developed by a consensus panel of experts from emergency medicine and suicide prevention organizations, as well as individuals who have lived through suicide attempts and suicidal thoughts or feelings.

The ED Guide is endorsed by the American Academy of Emergency Medicine, American Association for Emergency Psychiatry, American Association of Suicidology, and the American Foundation for Suicide Prevention.

SAMHSA’s National Survey on Drug Use and Health indicates that 1.3 million adults aged 18 or older (0.6 percent) attempted suicide in the past year. According to the Centers for Disease Control and Prevention, more than 41,000 individuals died by suicide in 2013. Suicides are the 10th leading cause of death in the U.S.

The ED Guide addresses specific objectives articulated by the 2012 National Strategy for Suicide Prevention, namely, to promote a continuum of care, safety, and well-being for ED patients treated for suicide risk; to collaborate with other health care providers to provide rapid and appropriate follow-up treatment; and to develop standardized protocols that direct clinical responses based on individual patient risk profiles.

The Suicide Prevention Resource Center (SPRC) has released Caring for Adult Patients with Suicide Risk: A Consensus Guide for Emergency Departments.

The Suicide Prevention Resource Center (SPRC) is the nation’s only federally-supported resource center devoted to advancing the National Strategy for Suicide Prevention. The guide includes evidence-based practices in decision support, initial interventions, and discharge planning for adults who have been identified as having some risk of suicide.

“Emergency departments are prime sites for suicide prevention activities in the U.S., but until now clinicians have not had tools to help them steer patients toward treatment options that best meet their health and safety needs,”  Pamela S. Hyde, Administrator of the Substance Abuse and Mental Health Services Administration (SAMHSA) said in a press release.

Funded by SAMHSA, the guide was based on a literature review and developed by a consensus panel of experts from emergency medicine and suicide prevention organizations, as well as individuals who have lived through suicide attempts and suicidal thoughts or feelings.

The ED Guide is endorsed by the American Academy of Emergency Medicine, American Association for Emergency Psychiatry, American Association of Suicidology, and the American Foundation for Suicide Prevention.

SAMHSA’s National Survey on Drug Use and Health indicates that 1.3 million adults aged 18 or older (0.6 percent) attempted suicide in the past year. According to the Centers for Disease Control and Prevention, more than 41,000 individuals died by suicide in 2013. Suicides are the 10th leading cause of death in the U.S.

The ED Guide addresses specific objectives articulated by the 2012 National Strategy for Suicide Prevention, namely, to promote a continuum of care, safety, and well-being for ED patients treated for suicide risk; to collaborate with other health care providers to provide rapid and appropriate follow-up treatment; and to develop standardized protocols that direct clinical responses based on individual patient risk profiles.

The Suicide Prevention Resource Center (SPRC) has released Caring for Adult Patients with Suicide Risk: A Consensus Guide for Emergency Departments.

The Suicide Prevention Resource Center (SPRC) is the nation’s only federally-supported resource center devoted to advancing the National Strategy for Suicide Prevention. The guide includes evidence-based practices in decision support, initial interventions, and discharge planning for adults who have been identified as having some risk of suicide.

“Emergency departments are prime sites for suicide prevention activities in the U.S., but until now clinicians have not had tools to help them steer patients toward treatment options that best meet their health and safety needs,”  Pamela S. Hyde, Administrator of the Substance Abuse and Mental Health Services Administration (SAMHSA) said in a press release.

Funded by SAMHSA, the guide was based on a literature review and developed by a consensus panel of experts from emergency medicine and suicide prevention organizations, as well as individuals who have lived through suicide attempts and suicidal thoughts or feelings.

The ED Guide is endorsed by the American Academy of Emergency Medicine, American Association for Emergency Psychiatry, American Association of Suicidology, and the American Foundation for Suicide Prevention.

SAMHSA’s National Survey on Drug Use and Health indicates that 1.3 million adults aged 18 or older (0.6 percent) attempted suicide in the past year. According to the Centers for Disease Control and Prevention, more than 41,000 individuals died by suicide in 2013. Suicides are the 10th leading cause of death in the U.S.

The ED Guide addresses specific objectives articulated by the 2012 National Strategy for Suicide Prevention, namely, to promote a continuum of care, safety, and well-being for ED patients treated for suicide risk; to collaborate with other health care providers to provide rapid and appropriate follow-up treatment; and to develop standardized protocols that direct clinical responses based on individual patient risk profiles.

In men, major depressive disorder has a negative impact on bone mineral density, a cross-sectional study shows.

The study included 928 men, aged 24-98. Each study participant’s ultradistal forearm, lumbar spine, total hip, and total body bone mineral density (BMD) (g/cm²) were measured using dual-energy x-ray absorptiometry. Clinicians queried patients on their history of major depressive disorder (MDD) and whether they were currently using antidepressants. Of the study population, 84 (9.1%) had a single manic episode, 50 (5.4%) had recurrent (at least two ) manic episodes, and 65 (7.0%) were using antidepressants.

Study participants with recurrent MDD had lower forearm, total hip, lumbar spine, and total body BMDs than study participants who had one manic episode or had no history of MDD. After age and weight adjustments, recurrent MDD was significantly associated with lower forearm and total body BMDs, with forearm BMDs having been 6.5% lower and total body BMDs having been 2.5% lower in study participants with recurrent MDD than in those with no history of MDD.

Those men who had experienced a single manic episode actually had higher forearm, total hip, and total body BMDs than men with no history of MDD. Also, single-episode MDD was positively associated with total hip BMD – a finding that Paivi H. Rauma, a PhD student and researcher at University of Eastern Finland, Kuopio, and her colleagues said they could not explain.

Among the study’s other results was that antidepressant use was associated with lower BMD for the men studied with the lowest body weights (between 75 kg and 110 kg).

“We found that MDD and antidepressant use were independently associated with BMD; however, separation of these two issues is difficult,” the researchers wrote. “In all, prevention of depression, its early detection, and appropriate medical care are important issues in the prevention and care of osteoporosis in men. Lastly, these data raise the issue of screening for BMD in risk populations.”

Read the full study in Journal of Musculoskeletal and Neuronal Interactions.

[email protected]

In men, major depressive disorder has a negative impact on bone mineral density, a cross-sectional study shows.

The study included 928 men, aged 24-98. Each study participant’s ultradistal forearm, lumbar spine, total hip, and total body bone mineral density (BMD) (g/cm²) were measured using dual-energy x-ray absorptiometry. Clinicians queried patients on their history of major depressive disorder (MDD) and whether they were currently using antidepressants. Of the study population, 84 (9.1%) had a single manic episode, 50 (5.4%) had recurrent (at least two ) manic episodes, and 65 (7.0%) were using antidepressants.

Study participants with recurrent MDD had lower forearm, total hip, lumbar spine, and total body BMDs than study participants who had one manic episode or had no history of MDD. After age and weight adjustments, recurrent MDD was significantly associated with lower forearm and total body BMDs, with forearm BMDs having been 6.5% lower and total body BMDs having been 2.5% lower in study participants with recurrent MDD than in those with no history of MDD.

Those men who had experienced a single manic episode actually had higher forearm, total hip, and total body BMDs than men with no history of MDD. Also, single-episode MDD was positively associated with total hip BMD – a finding that Paivi H. Rauma, a PhD student and researcher at University of Eastern Finland, Kuopio, and her colleagues said they could not explain.

Among the study’s other results was that antidepressant use was associated with lower BMD for the men studied with the lowest body weights (between 75 kg and 110 kg).

“We found that MDD and antidepressant use were independently associated with BMD; however, separation of these two issues is difficult,” the researchers wrote. “In all, prevention of depression, its early detection, and appropriate medical care are important issues in the prevention and care of osteoporosis in men. Lastly, these data raise the issue of screening for BMD in risk populations.”

Read the full study in Journal of Musculoskeletal and Neuronal Interactions.

[email protected]

In men, major depressive disorder has a negative impact on bone mineral density, a cross-sectional study shows.

The study included 928 men, aged 24-98. Each study participant’s ultradistal forearm, lumbar spine, total hip, and total body bone mineral density (BMD) (g/cm²) were measured using dual-energy x-ray absorptiometry. Clinicians queried patients on their history of major depressive disorder (MDD) and whether they were currently using antidepressants. Of the study population, 84 (9.1%) had a single manic episode, 50 (5.4%) had recurrent (at least two ) manic episodes, and 65 (7.0%) were using antidepressants.

Study participants with recurrent MDD had lower forearm, total hip, lumbar spine, and total body BMDs than study participants who had one manic episode or had no history of MDD. After age and weight adjustments, recurrent MDD was significantly associated with lower forearm and total body BMDs, with forearm BMDs having been 6.5% lower and total body BMDs having been 2.5% lower in study participants with recurrent MDD than in those with no history of MDD.

Those men who had experienced a single manic episode actually had higher forearm, total hip, and total body BMDs than men with no history of MDD. Also, single-episode MDD was positively associated with total hip BMD – a finding that Paivi H. Rauma, a PhD student and researcher at University of Eastern Finland, Kuopio, and her colleagues said they could not explain.

Among the study’s other results was that antidepressant use was associated with lower BMD for the men studied with the lowest body weights (between 75 kg and 110 kg).

“We found that MDD and antidepressant use were independently associated with BMD; however, separation of these two issues is difficult,” the researchers wrote. “In all, prevention of depression, its early detection, and appropriate medical care are important issues in the prevention and care of osteoporosis in men. Lastly, these data raise the issue of screening for BMD in risk populations.”

Read the full study in Journal of Musculoskeletal and Neuronal Interactions.

[email protected]

For you, the first visits with a newborn are a busy balancing act of gentle physical exam and empathic parent reassurance and education. It’s difficult to imagine that much else could fit into these visits. But your providing weekly and then monthly checks on a newborn puts you in a unique position to detect postpartum depression in that baby’s mother (as are obstetricians at the 6-week follow up). Postpartum depression is relatively common and very treatable, but it can go untreated because of the silence that is often grounded in shame and stigma. A few days of “baby blues” secondary to being tired and hormonal changes is quite different from persistent postpartum depression. Early detection of postpartum depression and referral to a psychiatrist can relieve extraordinary suffering in a parent and stress in a family, and can protect the critical relationship developing between mother and baby.

Postpartum depression was rarely discussed as recently as 30 years ago; it was not formally recognized by psychiatrists as a distinct illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) until its fourth edition, released in 1994. It is only slightly more common than depression in nonpregnant women of childbearing age: the Centers for Disease Control and Prevention estimated that depression affects 13% of women in the postpartum period, compared with 11% of age-matched controls. It is, however, more likely to be severe than depression in the nonperipartum woman (Gen. Hosp. Psychiatry 2004;26:289-95).Teenage mothers, women with a personal or family history of depression, women giving birth to twins or triplets, women with a history of miscarriage or stillbirth, and women who experienced premature labor and delivery all appear to be at elevated risk for postpartum depression. While other stressors such as marital conflict, single parenthood, or financial strain are challenging for new mothers, they have not been shown to significantly increase the risk of postpartum depression. It also should be noted that a history of previous deliveries without a postpartum mood disorder is not protective or predictive.

The diagnostic criteria for postpartum depression are the same as for a major depressive episode, except that symptoms start in the 4 weeks after the delivery of a baby (although they may be present during the pregnancy or may not be noted until weeks or months later). This can make it easy to mistake depression for the “baby blues” – a period of weepiness, anxiety, moodiness, and exhaustion that commonly occurs to new mothers. These symptoms affect as many as 75% of mothers in the first few days after delivery and can be very unsettling, but the symptoms always improve within 2 weeks, whereas postpartum depression will persist or worsen. Although it can be severe, postpartum depression will improve with treatment, typically psychotherapy and possibly medication. Without treatment, postpartum depression can persist for months. It may remit spontaneously after a substantial period, but it also may worsen. Untreated postpartum depression can (rarely) deteriorate into postpartum psychosis, which usually requires hospitalization and more significant psychopharmacologic intervention. Failure to detect and treat depression in new mothers can lead to a number of complications for the mother, ranging from difficulty with breastfeeding and forming an attachment with her newborn to an inability to return to work. It also raises the risk for suicide, which accounts for 20% of all deaths in the postpartum population (Arch. Womens Ment. Health 2005;8:77-87).The catastrophe of infanticide is diminishingly rare, but almost always associated with untreated postpartum depression or psychosis.

The complications of untreated depression do not affect only the symptomatic mother. There have been many studies that have demonstrated the negative developmental effects of maternal depression on children of all ages, from infancy through adolescence. Maternal depression in the newborn period can be especially disruptive of development, as it can interfere with healthy attachment and an infant’s development of the fundamentals of self-regulation. Infants of depressed mothers are more likely to be passive, withdrawn, and dysregulated. Cognitive development in infants and toddlers of depressed mothers is frequently delayed. Toddler children of depressed mothers more frequently display internalizing (depressed and anxious) and externalizing (disruptive) behavioral symptoms. Mood, anxiety, conduct disorders, and attention-deficit/hyperactivity disorder are more common in the school-age and adolescent children of depressed mothers than in peers whose mothers are not depressed (Paediatr. Child Health 2004;9:575-83). Clearly, the consequences of untreated depression in a mother on even the youngest children can be profound and persistent. And, most importantly, they are preventable.

Why would new mothers experiencing such uncomfortable symptoms fail to actively seek help? There are many reasons for their silent suffering. Many new mothers assume that their symptoms are the “baby blues,” a normal part of the monumental adjustment from pregnancy to motherhood. When their symptoms fail to improve in the first few weeks as promised by friends or clinicians, they often assume that they are personally inadequate, not up to the task of parenting. Such feelings of worthlessness and guilt are actually common symptoms of depression, and contribute to the shame and silence that accompany depressive disorders. (This is one of the reasons depression is described as an “internalizing” disorder.) These feelings (or symptoms) of guilt often are heightened by popular expectations that new mothers should be experiencing delight and joy in the new child. While all of the attention was on the mother during her pregnancy, the focus of friends, family, and clinicians usually shifts entirely to the infant after delivery. Although the reality of postpartum depression is more comfortably and openly discussed now than a generation ago, these forces continue to compel most women suffering from depression to remain silent.

This is where you are in a unique position to facilitate the recognition and treatment of postpartum depression. While a new mother may have one follow-up visit with her obstetrician, she often will visit you weekly for the first month and monthly for the first 6 months of her infant’s life. These visits are structured around questions about routines of sleeping and eating, the mechanics of breastfeeding, and growing connection with the newborn. You are in a natural position to ask nonjudgmentally about these things, and to follow-up on suggestions that a mother’s sleep, appetite, and energy are problematic with a few screening questions. If it sounds to you like there may be postpartum depression, you are in a powerful position to point out that these feelings do not reflect inadequacy, but rather a common and treatable problem in new mothers. You are uniquely qualified to suggest to the guilt-ridden mother that it is not selfish to seek her own treatment, but it is critical to the healthy development of her newborn and other children, much like the routine airline warning that parents must put on their own oxygen masks before attempting to place the masks on their children. Indeed, the American Academy of Pediatrics recommended in a 2010 report that pediatricians screen new mothers for postpartum depression at the 1-, 2-, and 4-month check-ups of their newborns (Pediatrics 2010;126:1032).

So how best to screen during a busy check-up? The AAP recommends the Edinburgh Postnatal Depression Screen (EPDS), an extensively validated 10-item questionnaire that a mother can fill out in the waiting room. Scoring is relatively fast and a cut-off at or above 10 points suggests a high risk of depression. The AAP also suggests using a “yes” answer to either of the following questions as a positive screen:

1. Over the past 2 weeks have you ever felt down, depressed, or hopeless?

2. Over the past 2 weeks have you felt little interest or pleasure in doing things?

Even without using specific questions or instruments, you can be vigilant for certain red flags. If a new mother reports that she is having difficulty falling asleep (despite the sleep deprivation that usually accompanies life with a newborn); if her appetite is decreasing despite breastfeeding; if she describes intense worries or doubts about the baby or motherhood that have persisted for more than a few days or that interfere with her function; if she reports that she is experiencing no feelings of happiness or pleasure with her infant; or if she describes feelings of hopelessness or recurring thoughts about death and dying, then you should be concerned that she may be suffering from postpartum depression. You might then suggest to the mother that these feelings may reflect postpartum depression, reassuring her that this is a common and treatable condition. When you calmly and comfortably discusses this topic, you provide hope and relief, dissolving some of the stigma that can surround psychiatric illness for mothers.

What to do once you have noted that a new mother may be suffering from postpartum depression? The problem is common enough that you may want to find a psychiatrist with an interest in postpartum depression and develop a collegial working relationship. It can be helpful to find out if the mother has ever seen a psychiatrist or therapist, as this can be an easy and effective referral for a comprehensive evaluation. If she does not already have a mental health provider, referring her to her primary care provider can be an efficient way to access a psychiatric evaluation. Many mothers will want to have more specialized treatment, especially as they consider the safety of medications while breastfeeding. Many academic medical centers will have psychiatrists who specialize in women’s health. Some states have created programs to facilitate access to treatment for mothers, such as Massachusetts Child Psychiatry Access Project (MCPAP) for Moms. There are several national organizations that provide online information about clinicians and other resources, such as Postpartum Support International, the American Psychological Association, and the CDC.

Finally, we have addressed depression in new mothers. But the rates of depression in new fathers also are higher than in age-matched controls. When a father is the primary parent and suggests problems with sleep and mood, asking the same questions, showing concern, and providing referral information can be just as important.

Remember, 13% of new mothers have postpartum depression, and the suffering of parent, family, and newborn is treatable. Unfortunately, many mothers do not get the help they need, as this condition has not been a priority of our health care system. You, the pediatrician or family physician, are in a unique position to make this a priority. You can detect depression in new parents, providing a critical link to treatment and relief for them, and protecting their children from potentially serious and preventable complications.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) program at the Vernon Cancer Center, Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston. E-mail them at [email protected].

For you, the first visits with a newborn are a busy balancing act of gentle physical exam and empathic parent reassurance and education. It’s difficult to imagine that much else could fit into these visits. But your providing weekly and then monthly checks on a newborn puts you in a unique position to detect postpartum depression in that baby’s mother (as are obstetricians at the 6-week follow up). Postpartum depression is relatively common and very treatable, but it can go untreated because of the silence that is often grounded in shame and stigma. A few days of “baby blues” secondary to being tired and hormonal changes is quite different from persistent postpartum depression. Early detection of postpartum depression and referral to a psychiatrist can relieve extraordinary suffering in a parent and stress in a family, and can protect the critical relationship developing between mother and baby.

Postpartum depression was rarely discussed as recently as 30 years ago; it was not formally recognized by psychiatrists as a distinct illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) until its fourth edition, released in 1994. It is only slightly more common than depression in nonpregnant women of childbearing age: the Centers for Disease Control and Prevention estimated that depression affects 13% of women in the postpartum period, compared with 11% of age-matched controls. It is, however, more likely to be severe than depression in the nonperipartum woman (Gen. Hosp. Psychiatry 2004;26:289-95).Teenage mothers, women with a personal or family history of depression, women giving birth to twins or triplets, women with a history of miscarriage or stillbirth, and women who experienced premature labor and delivery all appear to be at elevated risk for postpartum depression. While other stressors such as marital conflict, single parenthood, or financial strain are challenging for new mothers, they have not been shown to significantly increase the risk of postpartum depression. It also should be noted that a history of previous deliveries without a postpartum mood disorder is not protective or predictive.

The diagnostic criteria for postpartum depression are the same as for a major depressive episode, except that symptoms start in the 4 weeks after the delivery of a baby (although they may be present during the pregnancy or may not be noted until weeks or months later). This can make it easy to mistake depression for the “baby blues” – a period of weepiness, anxiety, moodiness, and exhaustion that commonly occurs to new mothers. These symptoms affect as many as 75% of mothers in the first few days after delivery and can be very unsettling, but the symptoms always improve within 2 weeks, whereas postpartum depression will persist or worsen. Although it can be severe, postpartum depression will improve with treatment, typically psychotherapy and possibly medication. Without treatment, postpartum depression can persist for months. It may remit spontaneously after a substantial period, but it also may worsen. Untreated postpartum depression can (rarely) deteriorate into postpartum psychosis, which usually requires hospitalization and more significant psychopharmacologic intervention. Failure to detect and treat depression in new mothers can lead to a number of complications for the mother, ranging from difficulty with breastfeeding and forming an attachment with her newborn to an inability to return to work. It also raises the risk for suicide, which accounts for 20% of all deaths in the postpartum population (Arch. Womens Ment. Health 2005;8:77-87).The catastrophe of infanticide is diminishingly rare, but almost always associated with untreated postpartum depression or psychosis.

The complications of untreated depression do not affect only the symptomatic mother. There have been many studies that have demonstrated the negative developmental effects of maternal depression on children of all ages, from infancy through adolescence. Maternal depression in the newborn period can be especially disruptive of development, as it can interfere with healthy attachment and an infant’s development of the fundamentals of self-regulation. Infants of depressed mothers are more likely to be passive, withdrawn, and dysregulated. Cognitive development in infants and toddlers of depressed mothers is frequently delayed. Toddler children of depressed mothers more frequently display internalizing (depressed and anxious) and externalizing (disruptive) behavioral symptoms. Mood, anxiety, conduct disorders, and attention-deficit/hyperactivity disorder are more common in the school-age and adolescent children of depressed mothers than in peers whose mothers are not depressed (Paediatr. Child Health 2004;9:575-83). Clearly, the consequences of untreated depression in a mother on even the youngest children can be profound and persistent. And, most importantly, they are preventable.

Why would new mothers experiencing such uncomfortable symptoms fail to actively seek help? There are many reasons for their silent suffering. Many new mothers assume that their symptoms are the “baby blues,” a normal part of the monumental adjustment from pregnancy to motherhood. When their symptoms fail to improve in the first few weeks as promised by friends or clinicians, they often assume that they are personally inadequate, not up to the task of parenting. Such feelings of worthlessness and guilt are actually common symptoms of depression, and contribute to the shame and silence that accompany depressive disorders. (This is one of the reasons depression is described as an “internalizing” disorder.) These feelings (or symptoms) of guilt often are heightened by popular expectations that new mothers should be experiencing delight and joy in the new child. While all of the attention was on the mother during her pregnancy, the focus of friends, family, and clinicians usually shifts entirely to the infant after delivery. Although the reality of postpartum depression is more comfortably and openly discussed now than a generation ago, these forces continue to compel most women suffering from depression to remain silent.

This is where you are in a unique position to facilitate the recognition and treatment of postpartum depression. While a new mother may have one follow-up visit with her obstetrician, she often will visit you weekly for the first month and monthly for the first 6 months of her infant’s life. These visits are structured around questions about routines of sleeping and eating, the mechanics of breastfeeding, and growing connection with the newborn. You are in a natural position to ask nonjudgmentally about these things, and to follow-up on suggestions that a mother’s sleep, appetite, and energy are problematic with a few screening questions. If it sounds to you like there may be postpartum depression, you are in a powerful position to point out that these feelings do not reflect inadequacy, but rather a common and treatable problem in new mothers. You are uniquely qualified to suggest to the guilt-ridden mother that it is not selfish to seek her own treatment, but it is critical to the healthy development of her newborn and other children, much like the routine airline warning that parents must put on their own oxygen masks before attempting to place the masks on their children. Indeed, the American Academy of Pediatrics recommended in a 2010 report that pediatricians screen new mothers for postpartum depression at the 1-, 2-, and 4-month check-ups of their newborns (Pediatrics 2010;126:1032).

So how best to screen during a busy check-up? The AAP recommends the Edinburgh Postnatal Depression Screen (EPDS), an extensively validated 10-item questionnaire that a mother can fill out in the waiting room. Scoring is relatively fast and a cut-off at or above 10 points suggests a high risk of depression. The AAP also suggests using a “yes” answer to either of the following questions as a positive screen:

1. Over the past 2 weeks have you ever felt down, depressed, or hopeless?

2. Over the past 2 weeks have you felt little interest or pleasure in doing things?

Even without using specific questions or instruments, you can be vigilant for certain red flags. If a new mother reports that she is having difficulty falling asleep (despite the sleep deprivation that usually accompanies life with a newborn); if her appetite is decreasing despite breastfeeding; if she describes intense worries or doubts about the baby or motherhood that have persisted for more than a few days or that interfere with her function; if she reports that she is experiencing no feelings of happiness or pleasure with her infant; or if she describes feelings of hopelessness or recurring thoughts about death and dying, then you should be concerned that she may be suffering from postpartum depression. You might then suggest to the mother that these feelings may reflect postpartum depression, reassuring her that this is a common and treatable condition. When you calmly and comfortably discusses this topic, you provide hope and relief, dissolving some of the stigma that can surround psychiatric illness for mothers.

What to do once you have noted that a new mother may be suffering from postpartum depression? The problem is common enough that you may want to find a psychiatrist with an interest in postpartum depression and develop a collegial working relationship. It can be helpful to find out if the mother has ever seen a psychiatrist or therapist, as this can be an easy and effective referral for a comprehensive evaluation. If she does not already have a mental health provider, referring her to her primary care provider can be an efficient way to access a psychiatric evaluation. Many mothers will want to have more specialized treatment, especially as they consider the safety of medications while breastfeeding. Many academic medical centers will have psychiatrists who specialize in women’s health. Some states have created programs to facilitate access to treatment for mothers, such as Massachusetts Child Psychiatry Access Project (MCPAP) for Moms. There are several national organizations that provide online information about clinicians and other resources, such as Postpartum Support International, the American Psychological Association, and the CDC.

Finally, we have addressed depression in new mothers. But the rates of depression in new fathers also are higher than in age-matched controls. When a father is the primary parent and suggests problems with sleep and mood, asking the same questions, showing concern, and providing referral information can be just as important.

Remember, 13% of new mothers have postpartum depression, and the suffering of parent, family, and newborn is treatable. Unfortunately, many mothers do not get the help they need, as this condition has not been a priority of our health care system. You, the pediatrician or family physician, are in a unique position to make this a priority. You can detect depression in new parents, providing a critical link to treatment and relief for them, and protecting their children from potentially serious and preventable complications.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) program at the Vernon Cancer Center, Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston. E-mail them at [email protected].

For you, the first visits with a newborn are a busy balancing act of gentle physical exam and empathic parent reassurance and education. It’s difficult to imagine that much else could fit into these visits. But your providing weekly and then monthly checks on a newborn puts you in a unique position to detect postpartum depression in that baby’s mother (as are obstetricians at the 6-week follow up). Postpartum depression is relatively common and very treatable, but it can go untreated because of the silence that is often grounded in shame and stigma. A few days of “baby blues” secondary to being tired and hormonal changes is quite different from persistent postpartum depression. Early detection of postpartum depression and referral to a psychiatrist can relieve extraordinary suffering in a parent and stress in a family, and can protect the critical relationship developing between mother and baby.

Postpartum depression was rarely discussed as recently as 30 years ago; it was not formally recognized by psychiatrists as a distinct illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) until its fourth edition, released in 1994. It is only slightly more common than depression in nonpregnant women of childbearing age: the Centers for Disease Control and Prevention estimated that depression affects 13% of women in the postpartum period, compared with 11% of age-matched controls. It is, however, more likely to be severe than depression in the nonperipartum woman (Gen. Hosp. Psychiatry 2004;26:289-95).Teenage mothers, women with a personal or family history of depression, women giving birth to twins or triplets, women with a history of miscarriage or stillbirth, and women who experienced premature labor and delivery all appear to be at elevated risk for postpartum depression. While other stressors such as marital conflict, single parenthood, or financial strain are challenging for new mothers, they have not been shown to significantly increase the risk of postpartum depression. It also should be noted that a history of previous deliveries without a postpartum mood disorder is not protective or predictive.

The diagnostic criteria for postpartum depression are the same as for a major depressive episode, except that symptoms start in the 4 weeks after the delivery of a baby (although they may be present during the pregnancy or may not be noted until weeks or months later). This can make it easy to mistake depression for the “baby blues” – a period of weepiness, anxiety, moodiness, and exhaustion that commonly occurs to new mothers. These symptoms affect as many as 75% of mothers in the first few days after delivery and can be very unsettling, but the symptoms always improve within 2 weeks, whereas postpartum depression will persist or worsen. Although it can be severe, postpartum depression will improve with treatment, typically psychotherapy and possibly medication. Without treatment, postpartum depression can persist for months. It may remit spontaneously after a substantial period, but it also may worsen. Untreated postpartum depression can (rarely) deteriorate into postpartum psychosis, which usually requires hospitalization and more significant psychopharmacologic intervention. Failure to detect and treat depression in new mothers can lead to a number of complications for the mother, ranging from difficulty with breastfeeding and forming an attachment with her newborn to an inability to return to work. It also raises the risk for suicide, which accounts for 20% of all deaths in the postpartum population (Arch. Womens Ment. Health 2005;8:77-87).The catastrophe of infanticide is diminishingly rare, but almost always associated with untreated postpartum depression or psychosis.

The complications of untreated depression do not affect only the symptomatic mother. There have been many studies that have demonstrated the negative developmental effects of maternal depression on children of all ages, from infancy through adolescence. Maternal depression in the newborn period can be especially disruptive of development, as it can interfere with healthy attachment and an infant’s development of the fundamentals of self-regulation. Infants of depressed mothers are more likely to be passive, withdrawn, and dysregulated. Cognitive development in infants and toddlers of depressed mothers is frequently delayed. Toddler children of depressed mothers more frequently display internalizing (depressed and anxious) and externalizing (disruptive) behavioral symptoms. Mood, anxiety, conduct disorders, and attention-deficit/hyperactivity disorder are more common in the school-age and adolescent children of depressed mothers than in peers whose mothers are not depressed (Paediatr. Child Health 2004;9:575-83). Clearly, the consequences of untreated depression in a mother on even the youngest children can be profound and persistent. And, most importantly, they are preventable.

Why would new mothers experiencing such uncomfortable symptoms fail to actively seek help? There are many reasons for their silent suffering. Many new mothers assume that their symptoms are the “baby blues,” a normal part of the monumental adjustment from pregnancy to motherhood. When their symptoms fail to improve in the first few weeks as promised by friends or clinicians, they often assume that they are personally inadequate, not up to the task of parenting. Such feelings of worthlessness and guilt are actually common symptoms of depression, and contribute to the shame and silence that accompany depressive disorders. (This is one of the reasons depression is described as an “internalizing” disorder.) These feelings (or symptoms) of guilt often are heightened by popular expectations that new mothers should be experiencing delight and joy in the new child. While all of the attention was on the mother during her pregnancy, the focus of friends, family, and clinicians usually shifts entirely to the infant after delivery. Although the reality of postpartum depression is more comfortably and openly discussed now than a generation ago, these forces continue to compel most women suffering from depression to remain silent.

This is where you are in a unique position to facilitate the recognition and treatment of postpartum depression. While a new mother may have one follow-up visit with her obstetrician, she often will visit you weekly for the first month and monthly for the first 6 months of her infant’s life. These visits are structured around questions about routines of sleeping and eating, the mechanics of breastfeeding, and growing connection with the newborn. You are in a natural position to ask nonjudgmentally about these things, and to follow-up on suggestions that a mother’s sleep, appetite, and energy are problematic with a few screening questions. If it sounds to you like there may be postpartum depression, you are in a powerful position to point out that these feelings do not reflect inadequacy, but rather a common and treatable problem in new mothers. You are uniquely qualified to suggest to the guilt-ridden mother that it is not selfish to seek her own treatment, but it is critical to the healthy development of her newborn and other children, much like the routine airline warning that parents must put on their own oxygen masks before attempting to place the masks on their children. Indeed, the American Academy of Pediatrics recommended in a 2010 report that pediatricians screen new mothers for postpartum depression at the 1-, 2-, and 4-month check-ups of their newborns (Pediatrics 2010;126:1032).

So how best to screen during a busy check-up? The AAP recommends the Edinburgh Postnatal Depression Screen (EPDS), an extensively validated 10-item questionnaire that a mother can fill out in the waiting room. Scoring is relatively fast and a cut-off at or above 10 points suggests a high risk of depression. The AAP also suggests using a “yes” answer to either of the following questions as a positive screen:

1. Over the past 2 weeks have you ever felt down, depressed, or hopeless?

2. Over the past 2 weeks have you felt little interest or pleasure in doing things?

Even without using specific questions or instruments, you can be vigilant for certain red flags. If a new mother reports that she is having difficulty falling asleep (despite the sleep deprivation that usually accompanies life with a newborn); if her appetite is decreasing despite breastfeeding; if she describes intense worries or doubts about the baby or motherhood that have persisted for more than a few days or that interfere with her function; if she reports that she is experiencing no feelings of happiness or pleasure with her infant; or if she describes feelings of hopelessness or recurring thoughts about death and dying, then you should be concerned that she may be suffering from postpartum depression. You might then suggest to the mother that these feelings may reflect postpartum depression, reassuring her that this is a common and treatable condition. When you calmly and comfortably discusses this topic, you provide hope and relief, dissolving some of the stigma that can surround psychiatric illness for mothers.

What to do once you have noted that a new mother may be suffering from postpartum depression? The problem is common enough that you may want to find a psychiatrist with an interest in postpartum depression and develop a collegial working relationship. It can be helpful to find out if the mother has ever seen a psychiatrist or therapist, as this can be an easy and effective referral for a comprehensive evaluation. If she does not already have a mental health provider, referring her to her primary care provider can be an efficient way to access a psychiatric evaluation. Many mothers will want to have more specialized treatment, especially as they consider the safety of medications while breastfeeding. Many academic medical centers will have psychiatrists who specialize in women’s health. Some states have created programs to facilitate access to treatment for mothers, such as Massachusetts Child Psychiatry Access Project (MCPAP) for Moms. There are several national organizations that provide online information about clinicians and other resources, such as Postpartum Support International, the American Psychological Association, and the CDC.

Finally, we have addressed depression in new mothers. But the rates of depression in new fathers also are higher than in age-matched controls. When a father is the primary parent and suggests problems with sleep and mood, asking the same questions, showing concern, and providing referral information can be just as important.

Remember, 13% of new mothers have postpartum depression, and the suffering of parent, family, and newborn is treatable. Unfortunately, many mothers do not get the help they need, as this condition has not been a priority of our health care system. You, the pediatrician or family physician, are in a unique position to make this a priority. You can detect depression in new parents, providing a critical link to treatment and relief for them, and protecting their children from potentially serious and preventable complications.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) program at the Vernon Cancer Center, Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston. E-mail them at [email protected].