Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

[email protected]

Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

[email protected]

Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

[email protected]

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at [email protected].

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at [email protected].

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at [email protected].

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.

“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”

The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.

New clinical content

“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.

However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”

Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.

Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”

Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.

FamVeld/Thinkstock

Developmental surveillance and screening

What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.”

Darrin Klimek/Thinkstock

As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.

A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.

“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.

The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.

Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”

Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”

Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”

Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.

It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.

Promoting lifelong health

Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”

SIphotography/Thinkstock

Research guides Bright Futures updates

The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.

The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.

The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”

When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.

There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.

When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.

And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”

Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.

A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.

Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.

The full 4th edition Bright Futures toolkit will be available for use in 2018.

Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.

[email protected]

*This article was updated on December 21, 2017

CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.

“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”

The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.

New clinical content

“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.

However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”

Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.

Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”

Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.

FamVeld/Thinkstock

Developmental surveillance and screening

What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.”

Darrin Klimek/Thinkstock

As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.

A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.

“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.

The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.

Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”

Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”

Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”

Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.

It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.

Promoting lifelong health

Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”

SIphotography/Thinkstock

Research guides Bright Futures updates

The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.

The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.

The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”

When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.

There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.

When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.

And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”

Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.

A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.

Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.

The full 4th edition Bright Futures toolkit will be available for use in 2018.

Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.

[email protected]

*This article was updated on December 21, 2017

CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.

“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”

The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.

New clinical content

“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.

However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”

Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.

Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”

Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.

FamVeld/Thinkstock

Developmental surveillance and screening

What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.”

Darrin Klimek/Thinkstock

As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.

A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.

“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.

The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.

Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”

Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”

Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”

Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.

It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.

Promoting lifelong health

Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”

SIphotography/Thinkstock

Research guides Bright Futures updates

The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.

The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.

The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”

When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.

There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.

When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.

And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”

Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.

A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.

Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.

The full 4th edition Bright Futures toolkit will be available for use in 2018.

Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.

[email protected]

*This article was updated on December 21, 2017

WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.

In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).

[email protected]

SOURCE: Young M et al. AES abstract 3.109.

WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.

In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).

[email protected]

SOURCE: Young M et al. AES abstract 3.109.

WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.

In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).

[email protected]

SOURCE: Young M et al. AES abstract 3.109.

Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.

Thinkstock

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Am J Infect Control. 2009 Apr;37(3):241-3.

2. J Hosp Infect. 2015 Sep;91(1):1-7.

3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever

Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.

Thinkstock

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Am J Infect Control. 2009 Apr;37(3):241-3.

2. J Hosp Infect. 2015 Sep;91(1):1-7.

3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever

Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.

Thinkstock

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Am J Infect Control. 2009 Apr;37(3):241-3.

2. J Hosp Infect. 2015 Sep;91(1):1-7.

3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever

The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.

The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.

Related: Food Insecurity Among Veterans

In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.

The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.

Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?

Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”

The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.

The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.

Related: Food Insecurity Among Veterans

In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.

The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.

Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?

Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”

The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.

The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.

Related: Food Insecurity Among Veterans

In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.

The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.

Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?

Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”

Gary E. Raskob, PhD

ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.

In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.

Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.

Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).

Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.

Patients and treatment

Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.

Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.

Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.

Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.

The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.

Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.

Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.

About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.

About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.

Results

The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.

This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).

“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”

The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).

The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).

“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”

Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).

The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).

“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”

Gary E. Raskob, PhD

ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.

In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.

Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.

Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).

Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.

Patients and treatment

Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.

Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.

Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.

Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.

The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.

Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.

Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.

About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.

About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.

Results

The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.

This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).

“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”

The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).

The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).

“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”

Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).

The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).

“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”

Gary E. Raskob, PhD

ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.

In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.

Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.

Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).

Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.

Patients and treatment

Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.

Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.

Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.

Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.

The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.

Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.

Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.

About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.

About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.

Results

The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.

This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).

“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”

The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).

The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).

“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”

Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).

The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).

“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”

Structure of RNA

The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.

The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.

Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.

The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.

The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.

As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.

Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.

With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.

“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.

“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”

About fitusiran

Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.

Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.

Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.

The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.

The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.

The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.

The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.

In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.

Structure of RNA

The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.

The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.

Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.

The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.

The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.

As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.

Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.

With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.

“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.

“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”

About fitusiran

Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.

Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.

Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.

The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.

The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.

The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.

The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.

In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.

Structure of RNA

The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.

The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.

Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.

The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.

The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.

As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.

Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.

With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.

“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.

“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”

About fitusiran

Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.

Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.

Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.

The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.

The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.

The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.

The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.

In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.