SCOTTSDALE, ARIZ. – Exercise is a cornerstone of treating postural orthostatic tachycardia syndrome, according to Dr. Deborah Tepper.

“Exercise training is really the hot new way to treat this disorder. It’s been found to be very effective,” she said at a symposium sponsored by the American Headache Society.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that causes symptoms resembling panic attacks, said Dr. Tepper, who is an internist at the Cleveland Clinic Neurological Center for Pain. Patients may report syncope, dizziness, palpitations, rapid or irregular breathing, fatigue, and chest pain, she said. But to be diagnosed with POTS, they must have an increase of at least 30 beats per minute within 10 minutes of standing or with the 60-degree tilt table test. Patients aged 12-19 years must have an increase in heart rate of at least 40 beats per minute. Blood pressure may drop or stay the same, but will not fall to the extent seen in orthostatic hypotension (that is, a systolic drop of 20 mm Hg or a diastolic fall of at least 10 mm Hg), Dr. Tepper noted.

Courtesy Wikimedia Commons/Adrian Pingstone/Creative Commons License

Deconditioning, chronic fatigue, anxiety, dehydration, and various medications increase the frequency and severity of POTS-related symptoms, Dr. Tepper said. Patients sometimes severely restrict exercise in an effort to control symptoms, but lying on the couch or going to bed “is the worst thing you can do with POTS,” she said. Instead, patients should start a graded exercise program by swimming or exercising in recumbent or seated positions. Exercise training increases the aldosterone-to-renin ratio, can reduce migraine, improves overall health and stamina, supports independent functioning, and can help restore the sleep-wake cycle.

Increasing salt and fluid intake and wearing compression socks also can improve symptoms – often to the extent that patients will not need new medications. But this conservative approach is inadequate in patients with risky occupations and is less effective when patients have frequent episodes of syncope, Dr. Tepper said.

“Beta-blockers remain an option if salts, fluids, and patient education are not enough,” she added.

Beta-blockers inhibit epinephrine release and therefore can improve the migraine and anxiety symptoms that can occur in patients with POTS, although they should not be used in patients with asthma, Dr. Tepper emphasized.

Medications such as fludrocortisone and midodrine should be reserved for patients with recurrent or resistant symptoms, according to Dr. Tepper. “Midodrine can be helpful in some people, although the evidence overall rates it as low to moderate,” she said. Midodrine is a direct vasoconstrictor and alpha-adrenergic agonist that increases vasomotor tone, but also can exacerbate headaches and may cause supine hypertension, urinary retention, and insomnia, she noted. Fludrocortisone increases plasma volume, but worsens migraine, increases fluid retention, and cannot be used in diabetic patients, she said.

Clinicians should refer patients for a cardiology evaluation if they do not improve or have risk factors such as a history of cardiac disease or a family history of sudden cardiac death, chest pain, a QRS interval of more than 120 ms, a corrected QT interval of more than 450 ms or less than 300 ms, or syncope with no warning or while lying down, Dr. Tepper said. She declared no conflicts of interest.

SCOTTSDALE, ARIZ. – Exercise is a cornerstone of treating postural orthostatic tachycardia syndrome, according to Dr. Deborah Tepper.

“Exercise training is really the hot new way to treat this disorder. It’s been found to be very effective,” she said at a symposium sponsored by the American Headache Society.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that causes symptoms resembling panic attacks, said Dr. Tepper, who is an internist at the Cleveland Clinic Neurological Center for Pain. Patients may report syncope, dizziness, palpitations, rapid or irregular breathing, fatigue, and chest pain, she said. But to be diagnosed with POTS, they must have an increase of at least 30 beats per minute within 10 minutes of standing or with the 60-degree tilt table test. Patients aged 12-19 years must have an increase in heart rate of at least 40 beats per minute. Blood pressure may drop or stay the same, but will not fall to the extent seen in orthostatic hypotension (that is, a systolic drop of 20 mm Hg or a diastolic fall of at least 10 mm Hg), Dr. Tepper noted.

Courtesy Wikimedia Commons/Adrian Pingstone/Creative Commons License

Deconditioning, chronic fatigue, anxiety, dehydration, and various medications increase the frequency and severity of POTS-related symptoms, Dr. Tepper said. Patients sometimes severely restrict exercise in an effort to control symptoms, but lying on the couch or going to bed “is the worst thing you can do with POTS,” she said. Instead, patients should start a graded exercise program by swimming or exercising in recumbent or seated positions. Exercise training increases the aldosterone-to-renin ratio, can reduce migraine, improves overall health and stamina, supports independent functioning, and can help restore the sleep-wake cycle.

Increasing salt and fluid intake and wearing compression socks also can improve symptoms – often to the extent that patients will not need new medications. But this conservative approach is inadequate in patients with risky occupations and is less effective when patients have frequent episodes of syncope, Dr. Tepper said.

“Beta-blockers remain an option if salts, fluids, and patient education are not enough,” she added.

Beta-blockers inhibit epinephrine release and therefore can improve the migraine and anxiety symptoms that can occur in patients with POTS, although they should not be used in patients with asthma, Dr. Tepper emphasized.

Medications such as fludrocortisone and midodrine should be reserved for patients with recurrent or resistant symptoms, according to Dr. Tepper. “Midodrine can be helpful in some people, although the evidence overall rates it as low to moderate,” she said. Midodrine is a direct vasoconstrictor and alpha-adrenergic agonist that increases vasomotor tone, but also can exacerbate headaches and may cause supine hypertension, urinary retention, and insomnia, she noted. Fludrocortisone increases plasma volume, but worsens migraine, increases fluid retention, and cannot be used in diabetic patients, she said.

Clinicians should refer patients for a cardiology evaluation if they do not improve or have risk factors such as a history of cardiac disease or a family history of sudden cardiac death, chest pain, a QRS interval of more than 120 ms, a corrected QT interval of more than 450 ms or less than 300 ms, or syncope with no warning or while lying down, Dr. Tepper said. She declared no conflicts of interest.

SCOTTSDALE, ARIZ. – Exercise is a cornerstone of treating postural orthostatic tachycardia syndrome, according to Dr. Deborah Tepper.

“Exercise training is really the hot new way to treat this disorder. It’s been found to be very effective,” she said at a symposium sponsored by the American Headache Society.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that causes symptoms resembling panic attacks, said Dr. Tepper, who is an internist at the Cleveland Clinic Neurological Center for Pain. Patients may report syncope, dizziness, palpitations, rapid or irregular breathing, fatigue, and chest pain, she said. But to be diagnosed with POTS, they must have an increase of at least 30 beats per minute within 10 minutes of standing or with the 60-degree tilt table test. Patients aged 12-19 years must have an increase in heart rate of at least 40 beats per minute. Blood pressure may drop or stay the same, but will not fall to the extent seen in orthostatic hypotension (that is, a systolic drop of 20 mm Hg or a diastolic fall of at least 10 mm Hg), Dr. Tepper noted.

Courtesy Wikimedia Commons/Adrian Pingstone/Creative Commons License

Deconditioning, chronic fatigue, anxiety, dehydration, and various medications increase the frequency and severity of POTS-related symptoms, Dr. Tepper said. Patients sometimes severely restrict exercise in an effort to control symptoms, but lying on the couch or going to bed “is the worst thing you can do with POTS,” she said. Instead, patients should start a graded exercise program by swimming or exercising in recumbent or seated positions. Exercise training increases the aldosterone-to-renin ratio, can reduce migraine, improves overall health and stamina, supports independent functioning, and can help restore the sleep-wake cycle.

Increasing salt and fluid intake and wearing compression socks also can improve symptoms – often to the extent that patients will not need new medications. But this conservative approach is inadequate in patients with risky occupations and is less effective when patients have frequent episodes of syncope, Dr. Tepper said.

“Beta-blockers remain an option if salts, fluids, and patient education are not enough,” she added.

Beta-blockers inhibit epinephrine release and therefore can improve the migraine and anxiety symptoms that can occur in patients with POTS, although they should not be used in patients with asthma, Dr. Tepper emphasized.

Medications such as fludrocortisone and midodrine should be reserved for patients with recurrent or resistant symptoms, according to Dr. Tepper. “Midodrine can be helpful in some people, although the evidence overall rates it as low to moderate,” she said. Midodrine is a direct vasoconstrictor and alpha-adrenergic agonist that increases vasomotor tone, but also can exacerbate headaches and may cause supine hypertension, urinary retention, and insomnia, she noted. Fludrocortisone increases plasma volume, but worsens migraine, increases fluid retention, and cannot be used in diabetic patients, she said.

Clinicians should refer patients for a cardiology evaluation if they do not improve or have risk factors such as a history of cardiac disease or a family history of sudden cardiac death, chest pain, a QRS interval of more than 120 ms, a corrected QT interval of more than 450 ms or less than 300 ms, or syncope with no warning or while lying down, Dr. Tepper said. She declared no conflicts of interest.

Team performing surgery

Credit: Piotr Bodzek

New research suggests that, as the duration of surgery increases, so does the risk of venous thromboembolism (VTE).

Compared with a surgical procedure of average duration, patients who underwent the longest procedures had a 1.27-fold increase in the risk of developing a VTE.

In 3 of the most common procedures—gall bladder removal, appendectomy, and gastric bypass—surgery duration was a significant, independent risk factor for VTE.

Though these results suggest an association between surgical time and VTE, the researchers said they could not confirm a causal relationship.

John Y.S. Kim, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, and his colleagues reported these findings in JAMA Surgery.

The researchers analyzed data from the American College of Surgeons National Surgical Quality Improvement Program to examine the association between surgical duration and the incidence of VTE.

The study included more than 1.4 million patients who had surgery under general anesthesia at 315 US hospitals from 2005 to 2011.

A total of 13,809 patients (0.96%) had a postoperative VTE, with 10,198 (0.71%) developing deep vein thrombosis and 4772 (0.33%) developing a pulmonary embolism.

The rates of each of these events consistently increased with the duration of the surgical procedure.

The researchers divided patients into 5 quintiles representing surgery duration. In the first quintile (representing the relatively shortest procedures), there were 2033 VTEs. This was followed by 2278 in the second quintile, 2478 in the third, 2960 in the fourth, and 4060 in the fifth.

Compared with the third quintile (which served as a reference), the odds ratio (OR) for developing VTE in the first quintile was 0.86 (P<0.01). In the second quintile, the OR was 0.98 (P=0.39). The fourth and fifth quintiles had ORs of 1.10 and 1.27, respectively (P<0.001 for both).

The association between VTE incidence and the longest procedures was significant in 82% of 1000 bootstrap samples. In this analysis, there was a significant association (P<0.001) between surgery duration and VTE for gynecologic, neurologic, otolaryngologic, urologic, and vascular procedures.

In each of the 3 most common procedures, surgery duration was a significant, independent risk factor for VTE. A 1-hour increase in surgical time carried an OR of 1.18 for gall bladder removal, 1.18

for appendectomy, and 1.26 for gastric bypass (P<0.05 for all).

The researchers said these results appear to validate the widely held, but not previously substantiated, belief that longer operations are associated with a higher risk of VTE. This information could help improve VTE risk modeling, enhance thromboprophylaxis guidelines, and better inform surgical decision making.

Team performing surgery

Credit: Piotr Bodzek

New research suggests that, as the duration of surgery increases, so does the risk of venous thromboembolism (VTE).

Compared with a surgical procedure of average duration, patients who underwent the longest procedures had a 1.27-fold increase in the risk of developing a VTE.

In 3 of the most common procedures—gall bladder removal, appendectomy, and gastric bypass—surgery duration was a significant, independent risk factor for VTE.

Though these results suggest an association between surgical time and VTE, the researchers said they could not confirm a causal relationship.

John Y.S. Kim, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, and his colleagues reported these findings in JAMA Surgery.

The researchers analyzed data from the American College of Surgeons National Surgical Quality Improvement Program to examine the association between surgical duration and the incidence of VTE.

The study included more than 1.4 million patients who had surgery under general anesthesia at 315 US hospitals from 2005 to 2011.

A total of 13,809 patients (0.96%) had a postoperative VTE, with 10,198 (0.71%) developing deep vein thrombosis and 4772 (0.33%) developing a pulmonary embolism.

The rates of each of these events consistently increased with the duration of the surgical procedure.

The researchers divided patients into 5 quintiles representing surgery duration. In the first quintile (representing the relatively shortest procedures), there were 2033 VTEs. This was followed by 2278 in the second quintile, 2478 in the third, 2960 in the fourth, and 4060 in the fifth.

Compared with the third quintile (which served as a reference), the odds ratio (OR) for developing VTE in the first quintile was 0.86 (P<0.01). In the second quintile, the OR was 0.98 (P=0.39). The fourth and fifth quintiles had ORs of 1.10 and 1.27, respectively (P<0.001 for both).

The association between VTE incidence and the longest procedures was significant in 82% of 1000 bootstrap samples. In this analysis, there was a significant association (P<0.001) between surgery duration and VTE for gynecologic, neurologic, otolaryngologic, urologic, and vascular procedures.

In each of the 3 most common procedures, surgery duration was a significant, independent risk factor for VTE. A 1-hour increase in surgical time carried an OR of 1.18 for gall bladder removal, 1.18

for appendectomy, and 1.26 for gastric bypass (P<0.05 for all).

The researchers said these results appear to validate the widely held, but not previously substantiated, belief that longer operations are associated with a higher risk of VTE. This information could help improve VTE risk modeling, enhance thromboprophylaxis guidelines, and better inform surgical decision making.

Team performing surgery

Credit: Piotr Bodzek

New research suggests that, as the duration of surgery increases, so does the risk of venous thromboembolism (VTE).

Compared with a surgical procedure of average duration, patients who underwent the longest procedures had a 1.27-fold increase in the risk of developing a VTE.

In 3 of the most common procedures—gall bladder removal, appendectomy, and gastric bypass—surgery duration was a significant, independent risk factor for VTE.

Though these results suggest an association between surgical time and VTE, the researchers said they could not confirm a causal relationship.

John Y.S. Kim, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, and his colleagues reported these findings in JAMA Surgery.

The researchers analyzed data from the American College of Surgeons National Surgical Quality Improvement Program to examine the association between surgical duration and the incidence of VTE.

The study included more than 1.4 million patients who had surgery under general anesthesia at 315 US hospitals from 2005 to 2011.

A total of 13,809 patients (0.96%) had a postoperative VTE, with 10,198 (0.71%) developing deep vein thrombosis and 4772 (0.33%) developing a pulmonary embolism.

The rates of each of these events consistently increased with the duration of the surgical procedure.

The researchers divided patients into 5 quintiles representing surgery duration. In the first quintile (representing the relatively shortest procedures), there were 2033 VTEs. This was followed by 2278 in the second quintile, 2478 in the third, 2960 in the fourth, and 4060 in the fifth.

Compared with the third quintile (which served as a reference), the odds ratio (OR) for developing VTE in the first quintile was 0.86 (P<0.01). In the second quintile, the OR was 0.98 (P=0.39). The fourth and fifth quintiles had ORs of 1.10 and 1.27, respectively (P<0.001 for both).

The association between VTE incidence and the longest procedures was significant in 82% of 1000 bootstrap samples. In this analysis, there was a significant association (P<0.001) between surgery duration and VTE for gynecologic, neurologic, otolaryngologic, urologic, and vascular procedures.

In each of the 3 most common procedures, surgery duration was a significant, independent risk factor for VTE. A 1-hour increase in surgical time carried an OR of 1.18 for gall bladder removal, 1.18

for appendectomy, and 1.26 for gastric bypass (P<0.05 for all).

The researchers said these results appear to validate the widely held, but not previously substantiated, belief that longer operations are associated with a higher risk of VTE. This information could help improve VTE risk modeling, enhance thromboprophylaxis guidelines, and better inform surgical decision making.

Doctor consults with a family

Credit: Rhoda Baer

The American Society of Hematology (ASH) has released a second list of 5 commonly used tests, treatments, and procedures that physicians and patients should question in certain circumstances.

The additional items join an initial list of practices released last year as part of the Choosing Wisely^® campaign, an initiative of the ABIM Foundation that aims to prompt conversations between patients and physicians about the necessity and potential harm of certain procedures.

These new “practices to question” are also highlighted in a manuscript published in Blood, which further describes the methods for developing the list and the evidentiary basis of the recommendations.

The new recommendations include:

1. Don’t treat with an anticoagulant for more than 3 months in a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor.
2. Don’t routinely transfuse patients with sickle cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication.
3. Don’t perform baseline or routine surveillance CT scans in patients with asymptomatic, early stage chronic lymphocytic leukemia.
4. Don’t test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pre-test probability of HIT.
5. Don’t treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.

The second Choosing Wisely list was developed using a rigorous evidence-based methodology that incorporated suggestions from ASH members and prioritized avoiding harm to patients above all other considerations.

“Unnecessary treatments or tests not only add waste to the healthcare system, but, in some cases, they also expose our patients to a risk of harm,” said Lisa Hicks, MD, of St Michael’s Hospital and the University of Toronto and chair of the ASH Choosing Wisely Task Force.

“ASH developed its second Choosing Wisely list to help hematologists manage the utilization and delivery of patient-care resources, and the society encourages hematologists to consider these recommendations in all facets of their work, including patient care, teaching, innovation, and research.”

The dominant guiding principle for ASH’s list is the concept of avoiding harm. The four other established guiding principles of ASH’s involvement in the Choosing Wisely campaign are strength of evidence, aggregate cost, frequency, and making recommendations within the purview of hematology. This year, the task force added a sixth overarching principle of potential impact in the field.

“Choosing Wisely set out to stimulate conversations about waste and overuse in our healthcare system,” said Richard J. Baron, MD, President and CEO of the ABIM Foundation.

“We’ve been fortunate to be joined in this effort by many dedicated partners—including ASH—who have committed to addressing unnecessary care in their specialty. ASH’s second Choosing Wisely list gives clinicians and patients a new and important tool to help inform their conversations about what care is best for the patient.”

Doctor consults with a family

Credit: Rhoda Baer

The American Society of Hematology (ASH) has released a second list of 5 commonly used tests, treatments, and procedures that physicians and patients should question in certain circumstances.

The additional items join an initial list of practices released last year as part of the Choosing Wisely^® campaign, an initiative of the ABIM Foundation that aims to prompt conversations between patients and physicians about the necessity and potential harm of certain procedures.

These new “practices to question” are also highlighted in a manuscript published in Blood, which further describes the methods for developing the list and the evidentiary basis of the recommendations.

The new recommendations include:

1. Don’t treat with an anticoagulant for more than 3 months in a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor.
2. Don’t routinely transfuse patients with sickle cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication.
3. Don’t perform baseline or routine surveillance CT scans in patients with asymptomatic, early stage chronic lymphocytic leukemia.
4. Don’t test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pre-test probability of HIT.
5. Don’t treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.

The second Choosing Wisely list was developed using a rigorous evidence-based methodology that incorporated suggestions from ASH members and prioritized avoiding harm to patients above all other considerations.

“Unnecessary treatments or tests not only add waste to the healthcare system, but, in some cases, they also expose our patients to a risk of harm,” said Lisa Hicks, MD, of St Michael’s Hospital and the University of Toronto and chair of the ASH Choosing Wisely Task Force.

“ASH developed its second Choosing Wisely list to help hematologists manage the utilization and delivery of patient-care resources, and the society encourages hematologists to consider these recommendations in all facets of their work, including patient care, teaching, innovation, and research.”

The dominant guiding principle for ASH’s list is the concept of avoiding harm. The four other established guiding principles of ASH’s involvement in the Choosing Wisely campaign are strength of evidence, aggregate cost, frequency, and making recommendations within the purview of hematology. This year, the task force added a sixth overarching principle of potential impact in the field.

“Choosing Wisely set out to stimulate conversations about waste and overuse in our healthcare system,” said Richard J. Baron, MD, President and CEO of the ABIM Foundation.

“We’ve been fortunate to be joined in this effort by many dedicated partners—including ASH—who have committed to addressing unnecessary care in their specialty. ASH’s second Choosing Wisely list gives clinicians and patients a new and important tool to help inform their conversations about what care is best for the patient.”

Doctor consults with a family

Credit: Rhoda Baer

The American Society of Hematology (ASH) has released a second list of 5 commonly used tests, treatments, and procedures that physicians and patients should question in certain circumstances.

The additional items join an initial list of practices released last year as part of the Choosing Wisely^® campaign, an initiative of the ABIM Foundation that aims to prompt conversations between patients and physicians about the necessity and potential harm of certain procedures.

These new “practices to question” are also highlighted in a manuscript published in Blood, which further describes the methods for developing the list and the evidentiary basis of the recommendations.

The new recommendations include:

1. Don’t treat with an anticoagulant for more than 3 months in a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor.
2. Don’t routinely transfuse patients with sickle cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication.
3. Don’t perform baseline or routine surveillance CT scans in patients with asymptomatic, early stage chronic lymphocytic leukemia.
4. Don’t test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pre-test probability of HIT.
5. Don’t treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.

The second Choosing Wisely list was developed using a rigorous evidence-based methodology that incorporated suggestions from ASH members and prioritized avoiding harm to patients above all other considerations.

“Unnecessary treatments or tests not only add waste to the healthcare system, but, in some cases, they also expose our patients to a risk of harm,” said Lisa Hicks, MD, of St Michael’s Hospital and the University of Toronto and chair of the ASH Choosing Wisely Task Force.

“ASH developed its second Choosing Wisely list to help hematologists manage the utilization and delivery of patient-care resources, and the society encourages hematologists to consider these recommendations in all facets of their work, including patient care, teaching, innovation, and research.”

The dominant guiding principle for ASH’s list is the concept of avoiding harm. The four other established guiding principles of ASH’s involvement in the Choosing Wisely campaign are strength of evidence, aggregate cost, frequency, and making recommendations within the purview of hematology. This year, the task force added a sixth overarching principle of potential impact in the field.

“Choosing Wisely set out to stimulate conversations about waste and overuse in our healthcare system,” said Richard J. Baron, MD, President and CEO of the ABIM Foundation.

“We’ve been fortunate to be joined in this effort by many dedicated partners—including ASH—who have committed to addressing unnecessary care in their specialty. ASH’s second Choosing Wisely list gives clinicians and patients a new and important tool to help inform their conversations about what care is best for the patient.”

T cells

Credit: NIAID

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

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

T cells

Credit: NIAID

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

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

T cells

Credit: NIAID

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

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

69%: the percentage of hospitals that had perfect compliance with the Leapfrog Group employer coalition’s safe practices for hand hygiene in its 2013 annual quality survey of 1,437 U.S. hospitals.

The CDC estimates 2 million patients annually acquire hospital-acquired infections (HAIs), often spread by contaminated hands of healthcare workers.

Urban hospitals performed better than rural hospitals in compliance with Leapfrog’s standard.

69%: the percentage of hospitals that had perfect compliance with the Leapfrog Group employer coalition’s safe practices for hand hygiene in its 2013 annual quality survey of 1,437 U.S. hospitals.

The CDC estimates 2 million patients annually acquire hospital-acquired infections (HAIs), often spread by contaminated hands of healthcare workers.

Urban hospitals performed better than rural hospitals in compliance with Leapfrog’s standard.

69%: the percentage of hospitals that had perfect compliance with the Leapfrog Group employer coalition’s safe practices for hand hygiene in its 2013 annual quality survey of 1,437 U.S. hospitals.

The CDC estimates 2 million patients annually acquire hospital-acquired infections (HAIs), often spread by contaminated hands of healthcare workers.

Urban hospitals performed better than rural hospitals in compliance with Leapfrog’s standard.

The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.

The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.

The rule will take effect June 30, 2015.

© Jupiterimages/Thinkstock

Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.

The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.

The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.

“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.

“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.

Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.

In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.

The rule also requires that labels be updated as they become outdated.

Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.

In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”

“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”

Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.

“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.

Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.

The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.

The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.

The rule will take effect June 30, 2015.

© Jupiterimages/Thinkstock

Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.

The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.

The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.

“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.

“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.

Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.

In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.

The rule also requires that labels be updated as they become outdated.

Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.

In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”

“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”

Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.

“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.

Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.

The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.

The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.

The rule will take effect June 30, 2015.

© Jupiterimages/Thinkstock

Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.

The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.

The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.

“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.

“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.

Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.

In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.

The rule also requires that labels be updated as they become outdated.

Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.

In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”

“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”

Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.

“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.

Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.

$167 billion: Amount of federal Medicaid reimbursement payments that hospitals will forego between 2013 and 2022 in states that have opted not to expand their state programs under the 2010 Affordable Care Act.

For every $1 a state spends on expanding Medicaid, $13.41 in federal funding flows into the state, according to a new report from the Urban Institute and Robert Wood Johnson Foundation.

$167 billion: Amount of federal Medicaid reimbursement payments that hospitals will forego between 2013 and 2022 in states that have opted not to expand their state programs under the 2010 Affordable Care Act.

For every $1 a state spends on expanding Medicaid, $13.41 in federal funding flows into the state, according to a new report from the Urban Institute and Robert Wood Johnson Foundation.

$167 billion: Amount of federal Medicaid reimbursement payments that hospitals will forego between 2013 and 2022 in states that have opted not to expand their state programs under the 2010 Affordable Care Act.

For every $1 a state spends on expanding Medicaid, $13.41 in federal funding flows into the state, according to a new report from the Urban Institute and Robert Wood Johnson Foundation.

UpToDate, a leading clinical decision support resource for physicians, in July added palliative care as the newest of its 22 medical specialties. The palliative care section covers a variety of topics focused on improving symptoms and providing best quality of life for patients with serious illnesses. The new service resulted from two years of extensive collaboration by a team of 100 leading palliative care specialists from around the world, led by Harvard Medical School palliative care physicians J. Andrew Billings, MD, and Susan D. Block, MD, reviewing and grading the body of research and scientific literature on palliative care.

UpToDate, a leading clinical decision support resource for physicians, in July added palliative care as the newest of its 22 medical specialties. The palliative care section covers a variety of topics focused on improving symptoms and providing best quality of life for patients with serious illnesses. The new service resulted from two years of extensive collaboration by a team of 100 leading palliative care specialists from around the world, led by Harvard Medical School palliative care physicians J. Andrew Billings, MD, and Susan D. Block, MD, reviewing and grading the body of research and scientific literature on palliative care.

UpToDate, a leading clinical decision support resource for physicians, in July added palliative care as the newest of its 22 medical specialties. The palliative care section covers a variety of topics focused on improving symptoms and providing best quality of life for patients with serious illnesses. The new service resulted from two years of extensive collaboration by a team of 100 leading palliative care specialists from around the world, led by Harvard Medical School palliative care physicians J. Andrew Billings, MD, and Susan D. Block, MD, reviewing and grading the body of research and scientific literature on palliative care.

A frequent referral to our pediatric infectious disease outpatient program at Boston Medical Center is the child with recurrent skin and soft tissue infection. Most often, the child is an infant, toddler, or adolescent; the child is otherwise well but has had two or three prior episodes of skin infection; the infections are typically peri-inguinal including the buttocks, but may involve the face, back, thighs, or scalp. The families are often frustrated and hoping for a solution. Are there effective strategies for reducing recurrences?

Several recent studies provide insights and can be helpful in forming an evidence-based approach that offers modest benefit for reducing the risk of recurrence. Most recently, Kaplan et al. (Clin. Inf. Dis. 2014;58:679-82) reported on a clinical trial of sodium hypochlorite bleach baths combined with hygienic measures (frequent hand washing with soap, cutting fingernails short, using towels or washcloths and clothing without sharing, and daily bathing or showering), compared with hygienic measures alone. The treatment group received twice-weekly hypochlorite baths with 5 mL household bleach (Clorox-Regular 6.0% hypochlorite) per gallon of bath water, followed by moisturizer. Most children were colonized with methicillin-resistant Staphylococcus aureus (MRSA)(approximately 70%) or methicillin-susceptible S. aureus (MSSA)(approximately 30%). In the 12-month follow-up, 20% of children had recurrent skin or soft tissue infection (SSTI). Risk factors for recurrence were young age (<6 years) and burden of colonization (number of colonized sites). A small, nonstatistically significant benefit was observed in the treatment group with a 17% incidence of SSTI, compared with 20.9% in controls (P = 0.15). The authors concluded a bleach bath plus hygiene measures was associated with about a 20% nonstatistically significant decrease in recurrent community-acquired SSTI. No adverse effects of bleach baths were identified.

A second open-label, randomized study by Fritz et al. (Clin. Inf. Dis. 2012;54:743-51) evaluated the value of individual decolonization, compared with household decolonization, in children 6 months through 20 years of age with prior community-acquired SSTI. Cases were randomized to individual decolonization regimens (hygiene, 2% mupirocin for 5 days and 4% chlorhexidine daily body washes) or to household decolonization. Staphylococcal colonization was evaluated at 1, 3, 6, and 12 months. No differences in the rate of eradication of S. aureus were observed between the two strategies, except at 3 months where a greater proportion of children randomized to household decolonization were culture negative. Despite the lack of impact on colonization, SSTI documented by a physician was less common in children where decolonization was householdwide. After 12 months, 36% of children in the household decolonization sites had recurrent SSTI, compared with 55% in the individual decolonization stratum (P = .03). The authors concluded that household decolonization reduces SSTI in both the individual and household contacts.

Another approach to decolonization has been the use of oral antibiotics in combination with mupirocin and hexachloradine. Although data are limited, Miller et al. (Antimicrob. Agents Chemother. 2012;56:1084-6) reported on a small cohort of 31 prospectively evaluated patients with recurrent community-acquired MRSA skin infections. Individuals received nasal mupirocin, topical hexachlorophene body wash, and an oral antibiotic based on susceptibility testing (doxycycline, minocycline, or trimethoprim-sulfamethoxazole). In the 6 months prior to enrollment, the mean rate of SSTI was three infections per person (range, 2-30). The mean number of MRSA infections after the intervention decreased significantly from 0.84 infections per month to 0.03 infections per month during the 5.2-month follow-up. In general, the regimens were well tolerated with minor gastrointestinal complaints. The authors concluded that the combination of systemic and topical antimicrobials was associated with subsequent decreases in community-acquired MRSA SSTI; however, they acknowledged that without a control group, they were unable to be certain that the decrease was due to the prescribed regimen.

Our current approach for children referred with recurrent SSTI is household decolonization with nasal mupirocin and daily hexachloradine baths or showers or hypochlorite baths. The mupirocin is prescribed for 5-10 days; the hexachloradine/hypochlorite baths, for several months. We also stress the need for hygiene, including washing towels and linens in hot water, and cleaning surfaces and items such as remote controls with hypochlorite solutions. Although the value of environmental decontamination is unknown, studies by Uhlemann et al. (PLOS ONE 2011;6: e22407) demonstrated excess contamination of household surfaces in homes of SSTI cases. If recurrences continue, the addition of an antimicrobial agent is considered. We reserve doxycycline for children over 8 years of age and prescribe trimethoprim-sulfamethoxazole for those younger than 8 years. We also will ask about pets although we are aware of only anecdotal reports where treating the family dog or cat has aborted recurrent disease in the patients.

In summary, recurrent SSTI is common, especially among young children. The burden of colonization appears related to both the risk for recurrent disease and the risk for transmission within the household. Reducing colonization is valuable for decreasing the incidence of recurrent SSTI both for the individual as well as the household members. The current strategies demonstrate modest success, but as many as 30%-40% of patients will continue to have recurrent SSTI. Education about the early signs of infection, early evaluation of SSTI, and appropriate management (topical treatment, incision and drainage, or systemic antibiotics) are successful strategies for limiting progression to invasive staphylococcal disease.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Yildirim is a fellow in pediatric infectious disease and an epidemiologist, at Boston Medical Center. To comment, e-mail Dr. Pelton and Dr. Yildirim at [email protected].

A frequent referral to our pediatric infectious disease outpatient program at Boston Medical Center is the child with recurrent skin and soft tissue infection. Most often, the child is an infant, toddler, or adolescent; the child is otherwise well but has had two or three prior episodes of skin infection; the infections are typically peri-inguinal including the buttocks, but may involve the face, back, thighs, or scalp. The families are often frustrated and hoping for a solution. Are there effective strategies for reducing recurrences?

Several recent studies provide insights and can be helpful in forming an evidence-based approach that offers modest benefit for reducing the risk of recurrence. Most recently, Kaplan et al. (Clin. Inf. Dis. 2014;58:679-82) reported on a clinical trial of sodium hypochlorite bleach baths combined with hygienic measures (frequent hand washing with soap, cutting fingernails short, using towels or washcloths and clothing without sharing, and daily bathing or showering), compared with hygienic measures alone. The treatment group received twice-weekly hypochlorite baths with 5 mL household bleach (Clorox-Regular 6.0% hypochlorite) per gallon of bath water, followed by moisturizer. Most children were colonized with methicillin-resistant Staphylococcus aureus (MRSA)(approximately 70%) or methicillin-susceptible S. aureus (MSSA)(approximately 30%). In the 12-month follow-up, 20% of children had recurrent skin or soft tissue infection (SSTI). Risk factors for recurrence were young age (<6 years) and burden of colonization (number of colonized sites). A small, nonstatistically significant benefit was observed in the treatment group with a 17% incidence of SSTI, compared with 20.9% in controls (P = 0.15). The authors concluded a bleach bath plus hygiene measures was associated with about a 20% nonstatistically significant decrease in recurrent community-acquired SSTI. No adverse effects of bleach baths were identified.

A second open-label, randomized study by Fritz et al. (Clin. Inf. Dis. 2012;54:743-51) evaluated the value of individual decolonization, compared with household decolonization, in children 6 months through 20 years of age with prior community-acquired SSTI. Cases were randomized to individual decolonization regimens (hygiene, 2% mupirocin for 5 days and 4% chlorhexidine daily body washes) or to household decolonization. Staphylococcal colonization was evaluated at 1, 3, 6, and 12 months. No differences in the rate of eradication of S. aureus were observed between the two strategies, except at 3 months where a greater proportion of children randomized to household decolonization were culture negative. Despite the lack of impact on colonization, SSTI documented by a physician was less common in children where decolonization was householdwide. After 12 months, 36% of children in the household decolonization sites had recurrent SSTI, compared with 55% in the individual decolonization stratum (P = .03). The authors concluded that household decolonization reduces SSTI in both the individual and household contacts.

Another approach to decolonization has been the use of oral antibiotics in combination with mupirocin and hexachloradine. Although data are limited, Miller et al. (Antimicrob. Agents Chemother. 2012;56:1084-6) reported on a small cohort of 31 prospectively evaluated patients with recurrent community-acquired MRSA skin infections. Individuals received nasal mupirocin, topical hexachlorophene body wash, and an oral antibiotic based on susceptibility testing (doxycycline, minocycline, or trimethoprim-sulfamethoxazole). In the 6 months prior to enrollment, the mean rate of SSTI was three infections per person (range, 2-30). The mean number of MRSA infections after the intervention decreased significantly from 0.84 infections per month to 0.03 infections per month during the 5.2-month follow-up. In general, the regimens were well tolerated with minor gastrointestinal complaints. The authors concluded that the combination of systemic and topical antimicrobials was associated with subsequent decreases in community-acquired MRSA SSTI; however, they acknowledged that without a control group, they were unable to be certain that the decrease was due to the prescribed regimen.

Our current approach for children referred with recurrent SSTI is household decolonization with nasal mupirocin and daily hexachloradine baths or showers or hypochlorite baths. The mupirocin is prescribed for 5-10 days; the hexachloradine/hypochlorite baths, for several months. We also stress the need for hygiene, including washing towels and linens in hot water, and cleaning surfaces and items such as remote controls with hypochlorite solutions. Although the value of environmental decontamination is unknown, studies by Uhlemann et al. (PLOS ONE 2011;6: e22407) demonstrated excess contamination of household surfaces in homes of SSTI cases. If recurrences continue, the addition of an antimicrobial agent is considered. We reserve doxycycline for children over 8 years of age and prescribe trimethoprim-sulfamethoxazole for those younger than 8 years. We also will ask about pets although we are aware of only anecdotal reports where treating the family dog or cat has aborted recurrent disease in the patients.

In summary, recurrent SSTI is common, especially among young children. The burden of colonization appears related to both the risk for recurrent disease and the risk for transmission within the household. Reducing colonization is valuable for decreasing the incidence of recurrent SSTI both for the individual as well as the household members. The current strategies demonstrate modest success, but as many as 30%-40% of patients will continue to have recurrent SSTI. Education about the early signs of infection, early evaluation of SSTI, and appropriate management (topical treatment, incision and drainage, or systemic antibiotics) are successful strategies for limiting progression to invasive staphylococcal disease.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Yildirim is a fellow in pediatric infectious disease and an epidemiologist, at Boston Medical Center. To comment, e-mail Dr. Pelton and Dr. Yildirim at [email protected].

A frequent referral to our pediatric infectious disease outpatient program at Boston Medical Center is the child with recurrent skin and soft tissue infection. Most often, the child is an infant, toddler, or adolescent; the child is otherwise well but has had two or three prior episodes of skin infection; the infections are typically peri-inguinal including the buttocks, but may involve the face, back, thighs, or scalp. The families are often frustrated and hoping for a solution. Are there effective strategies for reducing recurrences?

Several recent studies provide insights and can be helpful in forming an evidence-based approach that offers modest benefit for reducing the risk of recurrence. Most recently, Kaplan et al. (Clin. Inf. Dis. 2014;58:679-82) reported on a clinical trial of sodium hypochlorite bleach baths combined with hygienic measures (frequent hand washing with soap, cutting fingernails short, using towels or washcloths and clothing without sharing, and daily bathing or showering), compared with hygienic measures alone. The treatment group received twice-weekly hypochlorite baths with 5 mL household bleach (Clorox-Regular 6.0% hypochlorite) per gallon of bath water, followed by moisturizer. Most children were colonized with methicillin-resistant Staphylococcus aureus (MRSA)(approximately 70%) or methicillin-susceptible S. aureus (MSSA)(approximately 30%). In the 12-month follow-up, 20% of children had recurrent skin or soft tissue infection (SSTI). Risk factors for recurrence were young age (<6 years) and burden of colonization (number of colonized sites). A small, nonstatistically significant benefit was observed in the treatment group with a 17% incidence of SSTI, compared with 20.9% in controls (P = 0.15). The authors concluded a bleach bath plus hygiene measures was associated with about a 20% nonstatistically significant decrease in recurrent community-acquired SSTI. No adverse effects of bleach baths were identified.

A second open-label, randomized study by Fritz et al. (Clin. Inf. Dis. 2012;54:743-51) evaluated the value of individual decolonization, compared with household decolonization, in children 6 months through 20 years of age with prior community-acquired SSTI. Cases were randomized to individual decolonization regimens (hygiene, 2% mupirocin for 5 days and 4% chlorhexidine daily body washes) or to household decolonization. Staphylococcal colonization was evaluated at 1, 3, 6, and 12 months. No differences in the rate of eradication of S. aureus were observed between the two strategies, except at 3 months where a greater proportion of children randomized to household decolonization were culture negative. Despite the lack of impact on colonization, SSTI documented by a physician was less common in children where decolonization was householdwide. After 12 months, 36% of children in the household decolonization sites had recurrent SSTI, compared with 55% in the individual decolonization stratum (P = .03). The authors concluded that household decolonization reduces SSTI in both the individual and household contacts.

Another approach to decolonization has been the use of oral antibiotics in combination with mupirocin and hexachloradine. Although data are limited, Miller et al. (Antimicrob. Agents Chemother. 2012;56:1084-6) reported on a small cohort of 31 prospectively evaluated patients with recurrent community-acquired MRSA skin infections. Individuals received nasal mupirocin, topical hexachlorophene body wash, and an oral antibiotic based on susceptibility testing (doxycycline, minocycline, or trimethoprim-sulfamethoxazole). In the 6 months prior to enrollment, the mean rate of SSTI was three infections per person (range, 2-30). The mean number of MRSA infections after the intervention decreased significantly from 0.84 infections per month to 0.03 infections per month during the 5.2-month follow-up. In general, the regimens were well tolerated with minor gastrointestinal complaints. The authors concluded that the combination of systemic and topical antimicrobials was associated with subsequent decreases in community-acquired MRSA SSTI; however, they acknowledged that without a control group, they were unable to be certain that the decrease was due to the prescribed regimen.

Our current approach for children referred with recurrent SSTI is household decolonization with nasal mupirocin and daily hexachloradine baths or showers or hypochlorite baths. The mupirocin is prescribed for 5-10 days; the hexachloradine/hypochlorite baths, for several months. We also stress the need for hygiene, including washing towels and linens in hot water, and cleaning surfaces and items such as remote controls with hypochlorite solutions. Although the value of environmental decontamination is unknown, studies by Uhlemann et al. (PLOS ONE 2011;6: e22407) demonstrated excess contamination of household surfaces in homes of SSTI cases. If recurrences continue, the addition of an antimicrobial agent is considered. We reserve doxycycline for children over 8 years of age and prescribe trimethoprim-sulfamethoxazole for those younger than 8 years. We also will ask about pets although we are aware of only anecdotal reports where treating the family dog or cat has aborted recurrent disease in the patients.

In summary, recurrent SSTI is common, especially among young children. The burden of colonization appears related to both the risk for recurrent disease and the risk for transmission within the household. Reducing colonization is valuable for decreasing the incidence of recurrent SSTI both for the individual as well as the household members. The current strategies demonstrate modest success, but as many as 30%-40% of patients will continue to have recurrent SSTI. Education about the early signs of infection, early evaluation of SSTI, and appropriate management (topical treatment, incision and drainage, or systemic antibiotics) are successful strategies for limiting progression to invasive staphylococcal disease.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Yildirim is a fellow in pediatric infectious disease and an epidemiologist, at Boston Medical Center. To comment, e-mail Dr. Pelton and Dr. Yildirim at [email protected].