A new treatment for amyotrophic lateral sclerosis (ALS), Radicava (edaravone), is on the way for U.S. patients.

“After learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States,” said Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is the first new treatment approved by the FDA for ALS in many years, and we are pleased that people with ALS will now have an additional option.”

In a 6-month trial, 137 patients were randomly assigned to edaravone or placebo. At week 24, those receiving edaravone had declined less on a clinical assessment of daily functioning.

Edaravon is given intravenously daily for 14 days to start, followed by 14 days drug free. Subsequent treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug free.

The most common adverse reactions are bruising and gait disturbance. Edaravon also contains sodium bisulfite, which can cause serious allergic reactions in patients with sulfite sensitivity.

A new treatment for amyotrophic lateral sclerosis (ALS), Radicava (edaravone), is on the way for U.S. patients.

“After learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States,” said Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is the first new treatment approved by the FDA for ALS in many years, and we are pleased that people with ALS will now have an additional option.”

In a 6-month trial, 137 patients were randomly assigned to edaravone or placebo. At week 24, those receiving edaravone had declined less on a clinical assessment of daily functioning.

Edaravon is given intravenously daily for 14 days to start, followed by 14 days drug free. Subsequent treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug free.

The most common adverse reactions are bruising and gait disturbance. Edaravon also contains sodium bisulfite, which can cause serious allergic reactions in patients with sulfite sensitivity.

A new treatment for amyotrophic lateral sclerosis (ALS), Radicava (edaravone), is on the way for U.S. patients.

“After learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States,” said Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is the first new treatment approved by the FDA for ALS in many years, and we are pleased that people with ALS will now have an additional option.”

In a 6-month trial, 137 patients were randomly assigned to edaravone or placebo. At week 24, those receiving edaravone had declined less on a clinical assessment of daily functioning.

Edaravon is given intravenously daily for 14 days to start, followed by 14 days drug free. Subsequent treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug free.

The most common adverse reactions are bruising and gait disturbance. Edaravon also contains sodium bisulfite, which can cause serious allergic reactions in patients with sulfite sensitivity.

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

Vials and a syringe

BERLIN—Results of a phase 3 study suggest prophylaxis with plasma-derived factor X (pdFX, Coagadex®) prevents or reduces bleeding episodes in children with moderate to severe hereditary factor X deficiency (FXD).

pdFX was well tolerated in this study as well, with no treatment-related adverse events (AEs) reported.

“For the first time, we have data providing physicians with important evidence of the efficacy and safety of Coagadex as a prophylactic regimen for the reduction and prevention of bleeding episodes, as well as potential guidance on dosing for children with hereditary factor X deficiency,” said Michael Gattens, MBChB, a consultant pediatric hematologist at Cambridge University Hospitals in the UK and an investigator involved in this trial.

Data from the trial, known as TEN02, were presented in a poster (PB 818) at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The trial was sponsored by Bio Products Laboratory Limited.

TEN02 was a prospective study conducted in children younger than 12 years with moderate or severe congenital FXD (basal plasma factor X activity <5 IU/dL at diagnosis) and either a history of severe bleeding or an F10 gene mutation causing a documented severe bleeding type.

The study enrolled 9 patients. Eight had severe FXD (FX:C <1 IU/dL), and 1 had moderate FXD (FX:C 1–5 IU/dL).

The patients’ mean age was 7.3 (range, 2.6 years to 11.9 years). Four patients were in the 0-5 age group, and 5 were in the 6-11 age group. Fifty-six percent of patients were female, 78% were Asian, and 22% were white.

The patients had a total of 21 prior bleeds, including overt (n=10), covert (n=9), and menorrhagic (n=2). The past bleeds were spontaneous (n=16) or caused by injury (n=2), menorrhagia (n=2), or surgery (n=2).

Treatment

Patients received 50 IU/kg of pdFX at visit 1 (baseline), followed 72 hours later by a second dose (visit 2). At the investigator’s discretion, visit 2 may have been conducted 48 hours after the first dose for subjects ages 0 to 5.

Following visit 2, patients used pdFX at 40-50 IU/kg as routine prophylaxis every 72 ± 2 hours or every 48 ± 2 hours for those age 0 to 5, at the investigator’s discretion. Dose and frequency were adjusted over the initial 6 weeks to maintain FX:C levels ≥5 IU/dL (with peak levels ≤120 IU/dL).

Treatment was continued for at least 26 weeks, with a minimum of 50 treatment days.

Following visit 2, patients returned to the study site for 3 additional visits (after 9-28, 29-42, and 50 treatment days/26 weeks; visits 3-5), during which time blood samples were collected to assess FX:C trough levels and vital signs and AEs were checked.

A final bolus dose of 50 IU/kg was administered during visit 5 to assess post-dose incremental recovery.

A dose of 25 IU/kg was recommended to treat minor bleeds, and 50 IU/kg was recommended for major bleeds. Treatment was to be repeated as often as necessary based on FX:C recovery levels and clinical need.

Nine patients completed 11 treatment cycles, including 2 patients who had 50 exposure days but less than 26 study weeks. These patients were re-screened and completed a second, per-protocol treatment cycle.

Results

A total of 537 prophylactic infusions were administered, with a mean dose of 38.6 IU/kg per patient.

Investigators rated the prophylactic efficacy of pdFX as “excellent.”

There were 10 bleeds in 3 patients. Four bleeds in 2 patients (both in the 6-11 age group) required treatment with a single infusion of pdFX (mean dose, 31.7±10.1 IU/kg).

The overall mean 30-minute incremental recovery was 1.66 IU/dL per IU/kg for patients’ baseline visit, 1.82 IU/dL per IU/kg for the end-of-study visit, and 1.74 IU/dL per IU/kg for both visits combined.

Incremental recovery was significantly lower in the 0-5 age group than the 6-11 age group:

• 1.45 vs 1.83 at baseline (P=0.027)
• 1.62 vs 1.99 at end of study (P=0.025)
• 1.53 vs 1.91 combined (P=0.001).

All patients had FX:C trough levels greater than 5% after visit 4 (days 29-42).

There were 28 AEs reported in 8 patients, but none of these events were considered related to treatment.

One patient did have 2 serious treatment-emergent AEs—lower respiratory tract infection and influenza.

There were no other serious AEs, no evidence of factor X inhibitor development, and no deaths.

Vials and a syringe

BERLIN—Results of a phase 3 study suggest prophylaxis with plasma-derived factor X (pdFX, Coagadex®) prevents or reduces bleeding episodes in children with moderate to severe hereditary factor X deficiency (FXD).

pdFX was well tolerated in this study as well, with no treatment-related adverse events (AEs) reported.

“For the first time, we have data providing physicians with important evidence of the efficacy and safety of Coagadex as a prophylactic regimen for the reduction and prevention of bleeding episodes, as well as potential guidance on dosing for children with hereditary factor X deficiency,” said Michael Gattens, MBChB, a consultant pediatric hematologist at Cambridge University Hospitals in the UK and an investigator involved in this trial.

Data from the trial, known as TEN02, were presented in a poster (PB 818) at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The trial was sponsored by Bio Products Laboratory Limited.

TEN02 was a prospective study conducted in children younger than 12 years with moderate or severe congenital FXD (basal plasma factor X activity <5 IU/dL at diagnosis) and either a history of severe bleeding or an F10 gene mutation causing a documented severe bleeding type.

The study enrolled 9 patients. Eight had severe FXD (FX:C <1 IU/dL), and 1 had moderate FXD (FX:C 1–5 IU/dL).

The patients’ mean age was 7.3 (range, 2.6 years to 11.9 years). Four patients were in the 0-5 age group, and 5 were in the 6-11 age group. Fifty-six percent of patients were female, 78% were Asian, and 22% were white.

The patients had a total of 21 prior bleeds, including overt (n=10), covert (n=9), and menorrhagic (n=2). The past bleeds were spontaneous (n=16) or caused by injury (n=2), menorrhagia (n=2), or surgery (n=2).

Treatment

Patients received 50 IU/kg of pdFX at visit 1 (baseline), followed 72 hours later by a second dose (visit 2). At the investigator’s discretion, visit 2 may have been conducted 48 hours after the first dose for subjects ages 0 to 5.

Following visit 2, patients used pdFX at 40-50 IU/kg as routine prophylaxis every 72 ± 2 hours or every 48 ± 2 hours for those age 0 to 5, at the investigator’s discretion. Dose and frequency were adjusted over the initial 6 weeks to maintain FX:C levels ≥5 IU/dL (with peak levels ≤120 IU/dL).

Treatment was continued for at least 26 weeks, with a minimum of 50 treatment days.

Following visit 2, patients returned to the study site for 3 additional visits (after 9-28, 29-42, and 50 treatment days/26 weeks; visits 3-5), during which time blood samples were collected to assess FX:C trough levels and vital signs and AEs were checked.

A final bolus dose of 50 IU/kg was administered during visit 5 to assess post-dose incremental recovery.

A dose of 25 IU/kg was recommended to treat minor bleeds, and 50 IU/kg was recommended for major bleeds. Treatment was to be repeated as often as necessary based on FX:C recovery levels and clinical need.

Nine patients completed 11 treatment cycles, including 2 patients who had 50 exposure days but less than 26 study weeks. These patients were re-screened and completed a second, per-protocol treatment cycle.

Results

A total of 537 prophylactic infusions were administered, with a mean dose of 38.6 IU/kg per patient.

Investigators rated the prophylactic efficacy of pdFX as “excellent.”

There were 10 bleeds in 3 patients. Four bleeds in 2 patients (both in the 6-11 age group) required treatment with a single infusion of pdFX (mean dose, 31.7±10.1 IU/kg).

The overall mean 30-minute incremental recovery was 1.66 IU/dL per IU/kg for patients’ baseline visit, 1.82 IU/dL per IU/kg for the end-of-study visit, and 1.74 IU/dL per IU/kg for both visits combined.

Incremental recovery was significantly lower in the 0-5 age group than the 6-11 age group:

• 1.45 vs 1.83 at baseline (P=0.027)
• 1.62 vs 1.99 at end of study (P=0.025)
• 1.53 vs 1.91 combined (P=0.001).

All patients had FX:C trough levels greater than 5% after visit 4 (days 29-42).

There were 28 AEs reported in 8 patients, but none of these events were considered related to treatment.

One patient did have 2 serious treatment-emergent AEs—lower respiratory tract infection and influenza.

There were no other serious AEs, no evidence of factor X inhibitor development, and no deaths.

Vials and a syringe

BERLIN—Results of a phase 3 study suggest prophylaxis with plasma-derived factor X (pdFX, Coagadex®) prevents or reduces bleeding episodes in children with moderate to severe hereditary factor X deficiency (FXD).

pdFX was well tolerated in this study as well, with no treatment-related adverse events (AEs) reported.

“For the first time, we have data providing physicians with important evidence of the efficacy and safety of Coagadex as a prophylactic regimen for the reduction and prevention of bleeding episodes, as well as potential guidance on dosing for children with hereditary factor X deficiency,” said Michael Gattens, MBChB, a consultant pediatric hematologist at Cambridge University Hospitals in the UK and an investigator involved in this trial.

Data from the trial, known as TEN02, were presented in a poster (PB 818) at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The trial was sponsored by Bio Products Laboratory Limited.

TEN02 was a prospective study conducted in children younger than 12 years with moderate or severe congenital FXD (basal plasma factor X activity <5 IU/dL at diagnosis) and either a history of severe bleeding or an F10 gene mutation causing a documented severe bleeding type.

The study enrolled 9 patients. Eight had severe FXD (FX:C <1 IU/dL), and 1 had moderate FXD (FX:C 1–5 IU/dL).

The patients’ mean age was 7.3 (range, 2.6 years to 11.9 years). Four patients were in the 0-5 age group, and 5 were in the 6-11 age group. Fifty-six percent of patients were female, 78% were Asian, and 22% were white.

The patients had a total of 21 prior bleeds, including overt (n=10), covert (n=9), and menorrhagic (n=2). The past bleeds were spontaneous (n=16) or caused by injury (n=2), menorrhagia (n=2), or surgery (n=2).

Treatment

Patients received 50 IU/kg of pdFX at visit 1 (baseline), followed 72 hours later by a second dose (visit 2). At the investigator’s discretion, visit 2 may have been conducted 48 hours after the first dose for subjects ages 0 to 5.

Following visit 2, patients used pdFX at 40-50 IU/kg as routine prophylaxis every 72 ± 2 hours or every 48 ± 2 hours for those age 0 to 5, at the investigator’s discretion. Dose and frequency were adjusted over the initial 6 weeks to maintain FX:C levels ≥5 IU/dL (with peak levels ≤120 IU/dL).

Treatment was continued for at least 26 weeks, with a minimum of 50 treatment days.

Following visit 2, patients returned to the study site for 3 additional visits (after 9-28, 29-42, and 50 treatment days/26 weeks; visits 3-5), during which time blood samples were collected to assess FX:C trough levels and vital signs and AEs were checked.

A final bolus dose of 50 IU/kg was administered during visit 5 to assess post-dose incremental recovery.

A dose of 25 IU/kg was recommended to treat minor bleeds, and 50 IU/kg was recommended for major bleeds. Treatment was to be repeated as often as necessary based on FX:C recovery levels and clinical need.

Nine patients completed 11 treatment cycles, including 2 patients who had 50 exposure days but less than 26 study weeks. These patients were re-screened and completed a second, per-protocol treatment cycle.

Results

A total of 537 prophylactic infusions were administered, with a mean dose of 38.6 IU/kg per patient.

Investigators rated the prophylactic efficacy of pdFX as “excellent.”

There were 10 bleeds in 3 patients. Four bleeds in 2 patients (both in the 6-11 age group) required treatment with a single infusion of pdFX (mean dose, 31.7±10.1 IU/kg).

The overall mean 30-minute incremental recovery was 1.66 IU/dL per IU/kg for patients’ baseline visit, 1.82 IU/dL per IU/kg for the end-of-study visit, and 1.74 IU/dL per IU/kg for both visits combined.

Incremental recovery was significantly lower in the 0-5 age group than the 6-11 age group:

• 1.45 vs 1.83 at baseline (P=0.027)
• 1.62 vs 1.99 at end of study (P=0.025)
• 1.53 vs 1.91 combined (P=0.001).

All patients had FX:C trough levels greater than 5% after visit 4 (days 29-42).

There were 28 AEs reported in 8 patients, but none of these events were considered related to treatment.

One patient did have 2 serious treatment-emergent AEs—lower respiratory tract infection and influenza.

There were no other serious AEs, no evidence of factor X inhibitor development, and no deaths.

Image courtesy of AFIP

MADRID—Long-term maintenance with ropeginterferon alfa-2b is feasible, effective, and well-tolerated in patients with polycythemia vera (PV), according to researchers.

In the ongoing phase 1/2 PEGINVERA study, patients have received ropeginterferon alfa-2b for a median of 4 years.

After the first 2 years, patients switched from bi-weekly dosing to receiving ropeginterferon alfa-2b once every 4 weeks.

None of the patients discontinued treatment after the switch, and many were able to maintain their best response.

Most adverse events (AEs) were mild, although there were several severe treatment-related AEs.

These results were presented in a poster (abstract P707) at the 22nd Congress of the European Hematology Association (EHA). The research was funded by AOP Orphan Pharmaceuticals AG.

The trial enrolled 51 patients, but the researchers reported results in the 29 patients who had completed 2 years of treatment and switched from bi-weekly dosing to receiving treatment once every 4 weeks.

All 29 patients remained on the 4-week schedule with a median observation period of roughly 2 years. The median monthly dose was 308 μg before the switch and 165 μg after.

At study entry, the patients’ median age was 58 (range, 40-80), and 76% were male. Their median spleen length was 12.8 cm (range, 8.0-22.0), and 34% of patients had prior treatment with hydroxyurea.

Patients’ median hematocrit was 45.40% (range, 36.9-53.8), their median platelet count was 431 G/L (range, 225-1016), their median leukocyte count was 11.1 G/L (range, 4.7-30.9), and their median JAKV617F allelic burden was 78% (range, 2-91.5).

Results

More than 80% of patients achieved a hematologic response, with more than 50% achieving a complete hematologic response. The same percentage of patients maintained their best hematologic response before and 6 months after switching to the 4-week schedule—51.7%.

More than 80% of patients achieved a molecular response, with nearly 20% achieving a complete molecular response. The percentage of patients maintaining their best molecular response was 62.1% before switching to the 4-week schedule and 58.6% 6 months after the switch.

The researchers said changes in hematocrit, platelet count, leukocyte count, and spleen size after the switch were “minimal and without clinical relevance.”

The median hematocrit changed from 42.3% to 42.6%, the median platelet count changed from 201.0 x 10⁹/L to 211.9 x 10⁹/L, the median leukocyte count changed from 5.0 x 10⁹/L to 5.6 x 10⁹/L, and the median spleen size changed from 12.8 cm to 12.4 cm.

The need for phlebotomy did not change, with 24.1% of patients requiring phlebotomy both before and 6 months after the switch.

The researchers also noted that ropeginterferon alfa-2b decreased mutant JAK2 allele burden in all of the patients over time, with the strongest effect observed in the second year of treatment.

After 2 years, most patients had a burden below 10%, and this was not affected by the change in dosing.

There were no cases of progression to myelofibrosis or leukemic transformation.

Seventy-one percent of AEs were mild, and 40.4% were considered likely related to ropeginterferon alfa-2b. The most frequent treatment-related AEs were arthralgia (29.4%) and fatigue (21.6%).

There were 34 severe AEs, 11 of which were related to ropeginterferon alfa-2b.

Image courtesy of AFIP

MADRID—Long-term maintenance with ropeginterferon alfa-2b is feasible, effective, and well-tolerated in patients with polycythemia vera (PV), according to researchers.

In the ongoing phase 1/2 PEGINVERA study, patients have received ropeginterferon alfa-2b for a median of 4 years.

After the first 2 years, patients switched from bi-weekly dosing to receiving ropeginterferon alfa-2b once every 4 weeks.

None of the patients discontinued treatment after the switch, and many were able to maintain their best response.

Most adverse events (AEs) were mild, although there were several severe treatment-related AEs.

These results were presented in a poster (abstract P707) at the 22nd Congress of the European Hematology Association (EHA). The research was funded by AOP Orphan Pharmaceuticals AG.

The trial enrolled 51 patients, but the researchers reported results in the 29 patients who had completed 2 years of treatment and switched from bi-weekly dosing to receiving treatment once every 4 weeks.

All 29 patients remained on the 4-week schedule with a median observation period of roughly 2 years. The median monthly dose was 308 μg before the switch and 165 μg after.

At study entry, the patients’ median age was 58 (range, 40-80), and 76% were male. Their median spleen length was 12.8 cm (range, 8.0-22.0), and 34% of patients had prior treatment with hydroxyurea.

Patients’ median hematocrit was 45.40% (range, 36.9-53.8), their median platelet count was 431 G/L (range, 225-1016), their median leukocyte count was 11.1 G/L (range, 4.7-30.9), and their median JAKV617F allelic burden was 78% (range, 2-91.5).

Results

More than 80% of patients achieved a hematologic response, with more than 50% achieving a complete hematologic response. The same percentage of patients maintained their best hematologic response before and 6 months after switching to the 4-week schedule—51.7%.

More than 80% of patients achieved a molecular response, with nearly 20% achieving a complete molecular response. The percentage of patients maintaining their best molecular response was 62.1% before switching to the 4-week schedule and 58.6% 6 months after the switch.

The researchers said changes in hematocrit, platelet count, leukocyte count, and spleen size after the switch were “minimal and without clinical relevance.”

The median hematocrit changed from 42.3% to 42.6%, the median platelet count changed from 201.0 x 10⁹/L to 211.9 x 10⁹/L, the median leukocyte count changed from 5.0 x 10⁹/L to 5.6 x 10⁹/L, and the median spleen size changed from 12.8 cm to 12.4 cm.

The need for phlebotomy did not change, with 24.1% of patients requiring phlebotomy both before and 6 months after the switch.

The researchers also noted that ropeginterferon alfa-2b decreased mutant JAK2 allele burden in all of the patients over time, with the strongest effect observed in the second year of treatment.

After 2 years, most patients had a burden below 10%, and this was not affected by the change in dosing.

There were no cases of progression to myelofibrosis or leukemic transformation.

Seventy-one percent of AEs were mild, and 40.4% were considered likely related to ropeginterferon alfa-2b. The most frequent treatment-related AEs were arthralgia (29.4%) and fatigue (21.6%).

There were 34 severe AEs, 11 of which were related to ropeginterferon alfa-2b.

Image courtesy of AFIP

MADRID—Long-term maintenance with ropeginterferon alfa-2b is feasible, effective, and well-tolerated in patients with polycythemia vera (PV), according to researchers.

In the ongoing phase 1/2 PEGINVERA study, patients have received ropeginterferon alfa-2b for a median of 4 years.

After the first 2 years, patients switched from bi-weekly dosing to receiving ropeginterferon alfa-2b once every 4 weeks.

None of the patients discontinued treatment after the switch, and many were able to maintain their best response.

Most adverse events (AEs) were mild, although there were several severe treatment-related AEs.

These results were presented in a poster (abstract P707) at the 22nd Congress of the European Hematology Association (EHA). The research was funded by AOP Orphan Pharmaceuticals AG.

The trial enrolled 51 patients, but the researchers reported results in the 29 patients who had completed 2 years of treatment and switched from bi-weekly dosing to receiving treatment once every 4 weeks.

All 29 patients remained on the 4-week schedule with a median observation period of roughly 2 years. The median monthly dose was 308 μg before the switch and 165 μg after.

At study entry, the patients’ median age was 58 (range, 40-80), and 76% were male. Their median spleen length was 12.8 cm (range, 8.0-22.0), and 34% of patients had prior treatment with hydroxyurea.

Patients’ median hematocrit was 45.40% (range, 36.9-53.8), their median platelet count was 431 G/L (range, 225-1016), their median leukocyte count was 11.1 G/L (range, 4.7-30.9), and their median JAKV617F allelic burden was 78% (range, 2-91.5).

Results

More than 80% of patients achieved a hematologic response, with more than 50% achieving a complete hematologic response. The same percentage of patients maintained their best hematologic response before and 6 months after switching to the 4-week schedule—51.7%.

More than 80% of patients achieved a molecular response, with nearly 20% achieving a complete molecular response. The percentage of patients maintaining their best molecular response was 62.1% before switching to the 4-week schedule and 58.6% 6 months after the switch.

The researchers said changes in hematocrit, platelet count, leukocyte count, and spleen size after the switch were “minimal and without clinical relevance.”

The median hematocrit changed from 42.3% to 42.6%, the median platelet count changed from 201.0 x 10⁹/L to 211.9 x 10⁹/L, the median leukocyte count changed from 5.0 x 10⁹/L to 5.6 x 10⁹/L, and the median spleen size changed from 12.8 cm to 12.4 cm.

The need for phlebotomy did not change, with 24.1% of patients requiring phlebotomy both before and 6 months after the switch.

The researchers also noted that ropeginterferon alfa-2b decreased mutant JAK2 allele burden in all of the patients over time, with the strongest effect observed in the second year of treatment.

After 2 years, most patients had a burden below 10%, and this was not affected by the change in dosing.

There were no cases of progression to myelofibrosis or leukemic transformation.

Seventy-one percent of AEs were mild, and 40.4% were considered likely related to ropeginterferon alfa-2b. The most frequent treatment-related AEs were arthralgia (29.4%) and fatigue (21.6%).

There were 34 severe AEs, 11 of which were related to ropeginterferon alfa-2b.

The FP diagnosed pruritic urticarial papules and plaques of pregnancy. PUPPP is usually diagnosed by its characteristic findings in the history and physical examination.

PUPPP typically presents as erythematous papules and plaques within striae (with periumbilical sparing) late in the third trimester. Extreme pruritus is a hallmark of PUPPP and is present in all patients. Abdominal striae are the most common initial symptoms. The lesions usually spread to the extremities and coalesce to form urticarial plaques.

General measures such as cool baths, frequent application of emollients, wet soaks, or cool packs applied to the skin provide some symptomatic relief. First-line pharmacologic therapy consists of topical steroids and oral antihistamines to alleviate symptoms.

In this case, the FP prescribed a mid-potency topical corticosteroid, 0.1% triamcinolone cream twice daily (pregnancy class B). The patient was given the choice of steroid vehicle and chose the cream over the ointment. Both vehicles work to treat PUPPP, but the one that will work best is the one the patient will actually use.

The FP also recommended over-the-counter diphenhydramine 25 mg for additional symptomatic relief of pruritus (pregnancy class B). At her following prenatal visit, the patient’s symptoms were about 80% better and she was tolerating the pruritus. She was relieved to learn that this condition would resolve after pregnancy.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ. Pruritic urticarial papules and plaques of pregnancy. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 467-470.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP diagnosed pruritic urticarial papules and plaques of pregnancy. PUPPP is usually diagnosed by its characteristic findings in the history and physical examination.

PUPPP typically presents as erythematous papules and plaques within striae (with periumbilical sparing) late in the third trimester. Extreme pruritus is a hallmark of PUPPP and is present in all patients. Abdominal striae are the most common initial symptoms. The lesions usually spread to the extremities and coalesce to form urticarial plaques.

General measures such as cool baths, frequent application of emollients, wet soaks, or cool packs applied to the skin provide some symptomatic relief. First-line pharmacologic therapy consists of topical steroids and oral antihistamines to alleviate symptoms.

In this case, the FP prescribed a mid-potency topical corticosteroid, 0.1% triamcinolone cream twice daily (pregnancy class B). The patient was given the choice of steroid vehicle and chose the cream over the ointment. Both vehicles work to treat PUPPP, but the one that will work best is the one the patient will actually use.

The FP also recommended over-the-counter diphenhydramine 25 mg for additional symptomatic relief of pruritus (pregnancy class B). At her following prenatal visit, the patient’s symptoms were about 80% better and she was tolerating the pruritus. She was relieved to learn that this condition would resolve after pregnancy.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ. Pruritic urticarial papules and plaques of pregnancy. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 467-470.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP diagnosed pruritic urticarial papules and plaques of pregnancy. PUPPP is usually diagnosed by its characteristic findings in the history and physical examination.

PUPPP typically presents as erythematous papules and plaques within striae (with periumbilical sparing) late in the third trimester. Extreme pruritus is a hallmark of PUPPP and is present in all patients. Abdominal striae are the most common initial symptoms. The lesions usually spread to the extremities and coalesce to form urticarial plaques.

General measures such as cool baths, frequent application of emollients, wet soaks, or cool packs applied to the skin provide some symptomatic relief. First-line pharmacologic therapy consists of topical steroids and oral antihistamines to alleviate symptoms.

In this case, the FP prescribed a mid-potency topical corticosteroid, 0.1% triamcinolone cream twice daily (pregnancy class B). The patient was given the choice of steroid vehicle and chose the cream over the ointment. Both vehicles work to treat PUPPP, but the one that will work best is the one the patient will actually use.

The FP also recommended over-the-counter diphenhydramine 25 mg for additional symptomatic relief of pruritus (pregnancy class B). At her following prenatal visit, the patient’s symptoms were about 80% better and she was tolerating the pruritus. She was relieved to learn that this condition would resolve after pregnancy.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ. Pruritic urticarial papules and plaques of pregnancy. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 467-470.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were detected in Europe and the United States, and these were presumptively linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. A molecular epidemiological analysis of microbial isolate genomes detected a “remarkable clonality of isolates” in almost all of the assessed patients with M. chimaera disease, which “strongly points to a common source of infection,” as reported online in The Lancet Infectious Diseases.

The analysis comprised 250 whole-genome sequencing datasets: 24 isolates from 21 cardiac surgery–related patients in Switzerland, Germany, the Netherlands, and the United Kingdom; 36 from 35 unrelated patients; 126 from LivaNova HCUs in use (85 water cultures, 41 air cultures); 13 from LivaNova HCUs returned to the production site in Germany for disinfection; 4 from the LivaNova production site (3 from newly produced HCUs, 1 from a water source); 2 from Maquet extracorporeal membrane oxygenation (ECMO) devices in use; 14 from Maquet HCUs in use; 15 from new Maquet HCUs sampled at the production site; and 7 from hospital water supplies in Switzerland, Germany, and the Netherlands, plus one M. chimaera DSM 44623–type strain, and eight M. intracellulare strains (from four unrelated patients from Germany and four published genomes).

Isolates were analyzed by next-generation whole-genome sequencing and compared with published M. chimaera genomes, according to Jakko van Ingen, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, and his colleagues. Phylogenetic analysis of these 250 isolates revealed two major M. chimaera groups. They found that all cardiac surgery–related patient isolates could be classified into group 1. They then did a subgroup analysis.

“Three distinct strains of M. chimaera appear to have contaminated the water systems of LivaNova HCUs at the production site, belonging to subgroups 1.1, 1.8, and 2.1,” the authors stated. However, most M. chimaera isolates from air samples taken near operating LivaNova HCUs and those of 23 of the 24 related patients belonged to subgroup 1.1.

“This finding further supports the presumed airborne transmission pathway leading to endocarditis, aortic graft infection, disseminated disease, and surgical site infections in the affected patients,” according to the authors (doi: 10.1016/S1473-3099[17]30324-9).

The results suggest “the possibility that the vast majority of cases of cardiothoracic surgery–related severe M. chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the United Kingdom, the United States, and Australia resulted from a single common source of infection: LivaNova HCUs that were most likely contaminated during production in Germany,” the researchers concluded.

The study was partly funded by the EU Horizon 2020 program, its FP7 program, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance. The authors reported having no relevant conflicts.

[email protected]

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were detected in Europe and the United States, and these were presumptively linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. A molecular epidemiological analysis of microbial isolate genomes detected a “remarkable clonality of isolates” in almost all of the assessed patients with M. chimaera disease, which “strongly points to a common source of infection,” as reported online in The Lancet Infectious Diseases.

The analysis comprised 250 whole-genome sequencing datasets: 24 isolates from 21 cardiac surgery–related patients in Switzerland, Germany, the Netherlands, and the United Kingdom; 36 from 35 unrelated patients; 126 from LivaNova HCUs in use (85 water cultures, 41 air cultures); 13 from LivaNova HCUs returned to the production site in Germany for disinfection; 4 from the LivaNova production site (3 from newly produced HCUs, 1 from a water source); 2 from Maquet extracorporeal membrane oxygenation (ECMO) devices in use; 14 from Maquet HCUs in use; 15 from new Maquet HCUs sampled at the production site; and 7 from hospital water supplies in Switzerland, Germany, and the Netherlands, plus one M. chimaera DSM 44623–type strain, and eight M. intracellulare strains (from four unrelated patients from Germany and four published genomes).

Isolates were analyzed by next-generation whole-genome sequencing and compared with published M. chimaera genomes, according to Jakko van Ingen, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, and his colleagues. Phylogenetic analysis of these 250 isolates revealed two major M. chimaera groups. They found that all cardiac surgery–related patient isolates could be classified into group 1. They then did a subgroup analysis.

“Three distinct strains of M. chimaera appear to have contaminated the water systems of LivaNova HCUs at the production site, belonging to subgroups 1.1, 1.8, and 2.1,” the authors stated. However, most M. chimaera isolates from air samples taken near operating LivaNova HCUs and those of 23 of the 24 related patients belonged to subgroup 1.1.

“This finding further supports the presumed airborne transmission pathway leading to endocarditis, aortic graft infection, disseminated disease, and surgical site infections in the affected patients,” according to the authors (doi: 10.1016/S1473-3099[17]30324-9).

The results suggest “the possibility that the vast majority of cases of cardiothoracic surgery–related severe M. chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the United Kingdom, the United States, and Australia resulted from a single common source of infection: LivaNova HCUs that were most likely contaminated during production in Germany,” the researchers concluded.

The study was partly funded by the EU Horizon 2020 program, its FP7 program, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance. The authors reported having no relevant conflicts.

[email protected]

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were detected in Europe and the United States, and these were presumptively linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. A molecular epidemiological analysis of microbial isolate genomes detected a “remarkable clonality of isolates” in almost all of the assessed patients with M. chimaera disease, which “strongly points to a common source of infection,” as reported online in The Lancet Infectious Diseases.

The analysis comprised 250 whole-genome sequencing datasets: 24 isolates from 21 cardiac surgery–related patients in Switzerland, Germany, the Netherlands, and the United Kingdom; 36 from 35 unrelated patients; 126 from LivaNova HCUs in use (85 water cultures, 41 air cultures); 13 from LivaNova HCUs returned to the production site in Germany for disinfection; 4 from the LivaNova production site (3 from newly produced HCUs, 1 from a water source); 2 from Maquet extracorporeal membrane oxygenation (ECMO) devices in use; 14 from Maquet HCUs in use; 15 from new Maquet HCUs sampled at the production site; and 7 from hospital water supplies in Switzerland, Germany, and the Netherlands, plus one M. chimaera DSM 44623–type strain, and eight M. intracellulare strains (from four unrelated patients from Germany and four published genomes).

Isolates were analyzed by next-generation whole-genome sequencing and compared with published M. chimaera genomes, according to Jakko van Ingen, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, and his colleagues. Phylogenetic analysis of these 250 isolates revealed two major M. chimaera groups. They found that all cardiac surgery–related patient isolates could be classified into group 1. They then did a subgroup analysis.

“Three distinct strains of M. chimaera appear to have contaminated the water systems of LivaNova HCUs at the production site, belonging to subgroups 1.1, 1.8, and 2.1,” the authors stated. However, most M. chimaera isolates from air samples taken near operating LivaNova HCUs and those of 23 of the 24 related patients belonged to subgroup 1.1.

“This finding further supports the presumed airborne transmission pathway leading to endocarditis, aortic graft infection, disseminated disease, and surgical site infections in the affected patients,” according to the authors (doi: 10.1016/S1473-3099[17]30324-9).

The results suggest “the possibility that the vast majority of cases of cardiothoracic surgery–related severe M. chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the United Kingdom, the United States, and Australia resulted from a single common source of infection: LivaNova HCUs that were most likely contaminated during production in Germany,” the researchers concluded.

The study was partly funded by the EU Horizon 2020 program, its FP7 program, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance. The authors reported having no relevant conflicts.

[email protected]

As many as 20% of children and adolescents experience a psychiatric disorder, with 50% of all lifetime psychiatric illnesses occurring by the age of 14 years. ADHD and depression are among the most common. The National Institutes of Health estimate that, in 2015, 3 million 12- to 17-year-old American children experienced a major depressive episode. Any illness that affects over 10% of adolescents will present regularly in the primary care provider’s office. It is important to know whom to screen and how to start treatment when your patient appears to be suffering from this serious but treatable condition.

While there are many screening instruments, it is important to be ready to ask patients diagnostic questions when your clinical suspicion of depression is high. In addition to asking about mood, sleep, appetite, energy, and the other DSM5 criteria of a major depressive episode, it is important to remember that teens with depression might present with irritability as much as sadness. While they lose interest in school, sports, or hobbies, they still may be distracted or cheered up by friends. And depressed teenagers who are usually high achievers still may be functioning adequately, although at a much lower level than usual.

JochenSchoenfeld/Thinkstock

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 at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

As many as 20% of children and adolescents experience a psychiatric disorder, with 50% of all lifetime psychiatric illnesses occurring by the age of 14 years. ADHD and depression are among the most common. The National Institutes of Health estimate that, in 2015, 3 million 12- to 17-year-old American children experienced a major depressive episode. Any illness that affects over 10% of adolescents will present regularly in the primary care provider’s office. It is important to know whom to screen and how to start treatment when your patient appears to be suffering from this serious but treatable condition.

While there are many screening instruments, it is important to be ready to ask patients diagnostic questions when your clinical suspicion of depression is high. In addition to asking about mood, sleep, appetite, energy, and the other DSM5 criteria of a major depressive episode, it is important to remember that teens with depression might present with irritability as much as sadness. While they lose interest in school, sports, or hobbies, they still may be distracted or cheered up by friends. And depressed teenagers who are usually high achievers still may be functioning adequately, although at a much lower level than usual.

JochenSchoenfeld/Thinkstock

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 at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

As many as 20% of children and adolescents experience a psychiatric disorder, with 50% of all lifetime psychiatric illnesses occurring by the age of 14 years. ADHD and depression are among the most common. The National Institutes of Health estimate that, in 2015, 3 million 12- to 17-year-old American children experienced a major depressive episode. Any illness that affects over 10% of adolescents will present regularly in the primary care provider’s office. It is important to know whom to screen and how to start treatment when your patient appears to be suffering from this serious but treatable condition.

While there are many screening instruments, it is important to be ready to ask patients diagnostic questions when your clinical suspicion of depression is high. In addition to asking about mood, sleep, appetite, energy, and the other DSM5 criteria of a major depressive episode, it is important to remember that teens with depression might present with irritability as much as sadness. While they lose interest in school, sports, or hobbies, they still may be distracted or cheered up by friends. And depressed teenagers who are usually high achievers still may be functioning adequately, although at a much lower level than usual.

JochenSchoenfeld/Thinkstock

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 at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

NEW ORLEANS – With the trade-off of an extra 24 hours for results, an enhanced protocol to culture clinically relevant urinary pathogens detected significantly more unique pathogens associated with urinary tract infection, compared with standard cultures, in a study of 150 women.

“What we were able to see is that for about 90% of the samples that were called negative by standard [approach], we were able to detect bacteria through our protocol,” said Travis K. Price, a PhD candidate in the department of microbiology and immunology at Loyola University, Chicago.

Typically, when a urine sample is cultured for a UTI at Loyola University Medical Center, the standard protocol is for the lab to test 1 mcL of urine using agar plates incubated aerobically for 24 hours, Mr. Price said. “When we’re testing the urinary microbiome, we expand on that protocol. We use 100 times more urine, different plates, different environmental conditions, and we hold them for 48 hours instead of 24.”

The investigators prospectively recruited 150 women coming in to the urogynecology clinic – half who felt they had a UTI that day, half who did not. “We wanted to understand if using our enhanced protocol was beneficial and essentially leading to better patient outcomes,” Mr. Price said at the annual meeting of the American Society for Microbiology.

“Among the women who felt they had a UTI, standard culture only picked up 50% of the pathogens we were picking up with our protocol,” Mr. Price said. “And when we looked closer, we realized most of that was Escherichia coli.” Excluding samples positive for E. coli, standard culture detected only 12% of UTI pathogens, he added, compared with 77% detected with the expanded quantitative protocol.

The expanded protocol detected significantly more unique pathogen species, 95, compared with 11 with standard cultures. In addition, of all the uropathogens detected by the new protocol, the standard protocol missed 67%, or 122 of the total 182.

In terms of clinical practicality, Mr. Price and his colleagues looked at “different conditions, multiple volumes of urine, different plates, 24 versus 48 hours – and at the end tried to figure out what is the least amount of work you can do to get the most information.” They then developed a streamlined protocol that involves 100 mcL of urine, a CNA agar plate that selects for gram-positive organisms, a MacConkey agar using 5% CO₂, and 48 hours of incubation. “It’s easy to implement,” he added. “The only issue is the longer incubation time could lead to delayed treatment, potentially.”

The streamlined protocol detected more uropathogens – 152 of the 182, for an 84% detection rate – compared with standard cultures, which detected 60 of the 182, or 33%.

The streamlined protocol markedly improved uropathogen detection, the authors wrote. “These findings support the necessity for an immediate change in urine culture procedures.”

Another aim of the study was to evaluate the optimal threshold for UTI colony counts. Traditionally, the cutoff is set at 105 colonies or greater for diagnosis of a UTI, Mr. Price said. “We found there were always higher pathogen colony counts in people who thought they had a UTI. But there wasn’t one threshold that would have caught all of these.”

Next, the investigators looked for a correlation between the colony count cutoff and clinical outcomes. “For people who had a colony count greater than 105 – typically, it was a gram-negative organism – most people were treated with an antibiotic, and a week later most people, 62%, reported feeling better,” Mr. Price said. “But people who didn’t have a pathogen greater than 105, some were not treated, and when we called them a week later, most reported they were not feeling better. ... This suggests this threshold is not actually appropriate.”

Going forward, the investigators just started a clinical trial using the enhanced culture to confirm whether or not their protocol leads to better outcomes for women with UTIs.

Mr. Price did not have any relevant disclosures.

NEW ORLEANS – With the trade-off of an extra 24 hours for results, an enhanced protocol to culture clinically relevant urinary pathogens detected significantly more unique pathogens associated with urinary tract infection, compared with standard cultures, in a study of 150 women.

“What we were able to see is that for about 90% of the samples that were called negative by standard [approach], we were able to detect bacteria through our protocol,” said Travis K. Price, a PhD candidate in the department of microbiology and immunology at Loyola University, Chicago.

Typically, when a urine sample is cultured for a UTI at Loyola University Medical Center, the standard protocol is for the lab to test 1 mcL of urine using agar plates incubated aerobically for 24 hours, Mr. Price said. “When we’re testing the urinary microbiome, we expand on that protocol. We use 100 times more urine, different plates, different environmental conditions, and we hold them for 48 hours instead of 24.”

The investigators prospectively recruited 150 women coming in to the urogynecology clinic – half who felt they had a UTI that day, half who did not. “We wanted to understand if using our enhanced protocol was beneficial and essentially leading to better patient outcomes,” Mr. Price said at the annual meeting of the American Society for Microbiology.

“Among the women who felt they had a UTI, standard culture only picked up 50% of the pathogens we were picking up with our protocol,” Mr. Price said. “And when we looked closer, we realized most of that was Escherichia coli.” Excluding samples positive for E. coli, standard culture detected only 12% of UTI pathogens, he added, compared with 77% detected with the expanded quantitative protocol.

The expanded protocol detected significantly more unique pathogen species, 95, compared with 11 with standard cultures. In addition, of all the uropathogens detected by the new protocol, the standard protocol missed 67%, or 122 of the total 182.

In terms of clinical practicality, Mr. Price and his colleagues looked at “different conditions, multiple volumes of urine, different plates, 24 versus 48 hours – and at the end tried to figure out what is the least amount of work you can do to get the most information.” They then developed a streamlined protocol that involves 100 mcL of urine, a CNA agar plate that selects for gram-positive organisms, a MacConkey agar using 5% CO₂, and 48 hours of incubation. “It’s easy to implement,” he added. “The only issue is the longer incubation time could lead to delayed treatment, potentially.”

The streamlined protocol detected more uropathogens – 152 of the 182, for an 84% detection rate – compared with standard cultures, which detected 60 of the 182, or 33%.

The streamlined protocol markedly improved uropathogen detection, the authors wrote. “These findings support the necessity for an immediate change in urine culture procedures.”

Another aim of the study was to evaluate the optimal threshold for UTI colony counts. Traditionally, the cutoff is set at 105 colonies or greater for diagnosis of a UTI, Mr. Price said. “We found there were always higher pathogen colony counts in people who thought they had a UTI. But there wasn’t one threshold that would have caught all of these.”

Next, the investigators looked for a correlation between the colony count cutoff and clinical outcomes. “For people who had a colony count greater than 105 – typically, it was a gram-negative organism – most people were treated with an antibiotic, and a week later most people, 62%, reported feeling better,” Mr. Price said. “But people who didn’t have a pathogen greater than 105, some were not treated, and when we called them a week later, most reported they were not feeling better. ... This suggests this threshold is not actually appropriate.”

Going forward, the investigators just started a clinical trial using the enhanced culture to confirm whether or not their protocol leads to better outcomes for women with UTIs.

Mr. Price did not have any relevant disclosures.

NEW ORLEANS – With the trade-off of an extra 24 hours for results, an enhanced protocol to culture clinically relevant urinary pathogens detected significantly more unique pathogens associated with urinary tract infection, compared with standard cultures, in a study of 150 women.

“What we were able to see is that for about 90% of the samples that were called negative by standard [approach], we were able to detect bacteria through our protocol,” said Travis K. Price, a PhD candidate in the department of microbiology and immunology at Loyola University, Chicago.

Typically, when a urine sample is cultured for a UTI at Loyola University Medical Center, the standard protocol is for the lab to test 1 mcL of urine using agar plates incubated aerobically for 24 hours, Mr. Price said. “When we’re testing the urinary microbiome, we expand on that protocol. We use 100 times more urine, different plates, different environmental conditions, and we hold them for 48 hours instead of 24.”

The investigators prospectively recruited 150 women coming in to the urogynecology clinic – half who felt they had a UTI that day, half who did not. “We wanted to understand if using our enhanced protocol was beneficial and essentially leading to better patient outcomes,” Mr. Price said at the annual meeting of the American Society for Microbiology.

“Among the women who felt they had a UTI, standard culture only picked up 50% of the pathogens we were picking up with our protocol,” Mr. Price said. “And when we looked closer, we realized most of that was Escherichia coli.” Excluding samples positive for E. coli, standard culture detected only 12% of UTI pathogens, he added, compared with 77% detected with the expanded quantitative protocol.

The expanded protocol detected significantly more unique pathogen species, 95, compared with 11 with standard cultures. In addition, of all the uropathogens detected by the new protocol, the standard protocol missed 67%, or 122 of the total 182.

In terms of clinical practicality, Mr. Price and his colleagues looked at “different conditions, multiple volumes of urine, different plates, 24 versus 48 hours – and at the end tried to figure out what is the least amount of work you can do to get the most information.” They then developed a streamlined protocol that involves 100 mcL of urine, a CNA agar plate that selects for gram-positive organisms, a MacConkey agar using 5% CO₂, and 48 hours of incubation. “It’s easy to implement,” he added. “The only issue is the longer incubation time could lead to delayed treatment, potentially.”

The streamlined protocol detected more uropathogens – 152 of the 182, for an 84% detection rate – compared with standard cultures, which detected 60 of the 182, or 33%.

The streamlined protocol markedly improved uropathogen detection, the authors wrote. “These findings support the necessity for an immediate change in urine culture procedures.”

Another aim of the study was to evaluate the optimal threshold for UTI colony counts. Traditionally, the cutoff is set at 105 colonies or greater for diagnosis of a UTI, Mr. Price said. “We found there were always higher pathogen colony counts in people who thought they had a UTI. But there wasn’t one threshold that would have caught all of these.”

Next, the investigators looked for a correlation between the colony count cutoff and clinical outcomes. “For people who had a colony count greater than 105 – typically, it was a gram-negative organism – most people were treated with an antibiotic, and a week later most people, 62%, reported feeling better,” Mr. Price said. “But people who didn’t have a pathogen greater than 105, some were not treated, and when we called them a week later, most reported they were not feeling better. ... This suggests this threshold is not actually appropriate.”

Going forward, the investigators just started a clinical trial using the enhanced culture to confirm whether or not their protocol leads to better outcomes for women with UTIs.

Mr. Price did not have any relevant disclosures.

Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.

“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”

©MattZ90/thinkstockphotos.com

[email protected]

Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.

“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”

©MattZ90/thinkstockphotos.com

[email protected]

Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.

“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”

©MattZ90/thinkstockphotos.com

[email protected]

A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.

“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).

The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.

They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.

While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.

In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.

However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).

In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”

Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.

A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.

“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).

The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.

They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.

While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.

In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.

However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).

In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”

Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.

A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.

“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).

The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.

They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.

While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.

In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.

However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).

In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”

Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.