Marcia Frellick

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advice to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advice to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advice to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advise to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advise to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

Children who have first-degree relatives with celiac disease (CD) may be at higher risk of developing CD before age 10 than previously thought, according to results of an analysis of 10-year follow-up data. This analysis also yielded a web-based prediction model to help with screening for CD in children.

Screening is recommended for children who have a first-degree relative with celiac disease (CD) because they have a much higher risk for CD, but it has been unclear when to screen such children and how frequently. The researchers, led by Caroline Meijer, MD, in the department of pediatrics and medical statistics at Leiden (the Netherlands) University Medical Center, wrote in Gastroenterology that a prediction model they developed can help parents and providers with those questions.

NormaF/ThinkStock

The researchers analyzed prospective data from 10 years of follow-up from the PreventCD birth cohort with 944 children genetically predisposed to celiac disease with at least one first-degree relative affected. The children were enrolled at birth between 2007 and 2010 in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain.

“The data of the follow-up of the PreventCD cohort at the mean age of 10 years offers a unique opportunity to study the natural development of CD in children from high risk families,” the authors wrote.

Children were assessed regularly from birth for CD development at specific intervals, including seven times during the first 3 years of age and once a year after that or at least once between March 2016 and March 2019.

The researchers monitored parent-reported health status, recorded weight and height and gluten consumption and serum IgA against anti-transglutaminase. They found that risk for CD differs by gender, age, and human leukocyte antigen (HLA-DQ) genes. Variables that significantly affected the risk were combined to develop a risk score.

The noted that CD affects as many as 1%-3% of the general population. Until recently, the lifetime risk of CD when a child has a first-degree CD connection was considered to be 5%-10%, with one review indicating a pooled prevalence of 7.5%. However, the investigators found that the cumulative incidence of CD was 7.5%, 16.6%, and 17.5% at 3, 8, and 10 years of age, respectively.

“Our data show that, at the age of 8 years, this is as high as 17%, emphasizing the importance of a sound advice for early screening,” Dr. Meijer and coauthors wrote. “We also confirm that CD develops in children with affected FDR at a very young age, as the mean age of diagnosis in our cohort was 4 years of age.”

They found that CD developed more often in girls (P = .0005). Data show that, at the age of 10 years, girls in the cohort have a 7.7% higher cumulative incidence compared to boys (21.5% vs 13.8%). CD also developed more often in HLA-DQ2 homozygous participants than in other HLA-risk groups (8-year cumulative incidence of 35.4% vs. the maximum of the other groups of 18.2%; P < .001).

Benjamin Lebwohl, MD, MS, said the study provides data that can help parents of a child with a family history of celiac disease.

“The results of the study include an estimate of celiac disease risk over time, based on the child’s age, number of affected relatives, and genetic test results. Using this information, the web-based prediction model provides advice on how often to test the child for celiac disease, based on the child’s risk of developing the condition in the years ahead,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University Medical Center, New York, said in an interview.

“Overall,” he said, “the study advances our understanding of the natural history of celiac disease among children with a family history and gives clinicians and families practical advice on when to test.”

Validation of the prediction model was done with data from the independent NeoCel cohort. In that cohort, all children were assessed regularly from birth for CD development at predefined intervals, in a similar way as in the PreventCD cohort.

The investigators concluded that children should be screened early in life and that screening should include HLA-DQ2/8-typing. If children are genetically predisposed to CD, they should get further personalized screening advice using the web-based prediction “app” developed by the investigators.

“If the prediction for CD development [according to the app] is higher than 10% in the next 2 years, we advise to repeat the screening after 6 months. If the prediction is between 5%-10%, the advice is to repeat the screening after 1 year and if the prediction is lower than 5%, to repeat the screening after 2 years.”

The study authors reported no relevant financial relationships. The work is supported by funding from the European Commission; the Azrieli Foundation; Deutsche Zöliakie Gesellschaft; Eurospital; Fondazione Celiachia; Fria Bröd Sweden; Instituto de Salud Carlos III; Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Komitet Badań Naukowych; Fundacja Nutricia; Hungarian Scientific Research Funds; and TAMOP; Stichting Coeliakie Onderzoek Nederland; Thermo Fisher Scientific; and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. Lebwohl reported having no relevant disclosures.

Qualitative interviews with a group of female physicians identified several concerns about fertility and family planning and how those concerns affected their career choices.

Among the findings in a new study were that all 16 women interviewed said medical school education surrounding fertility was inadequate. Many said students should get comprehensive information about fertility’s decline with age and fertility preservation options and that information should be presented early in medical training so students can make choices. Yet, such issues are rarely discussed as part of medical training.

“[I]t would also be helpful for medical students and trainees to know what their options are, what insurance covers ... It wasn’t even touched at my orientation,” said one participant.

The findings from the hour-long interviews were used to build a survey. In a pilot test of the survey on 24 female physicians, researchers found that 71% had delayed childbearing and 67% had altered their careers to build families.

Kathryn S. Smith of Northwestern University, Chicago, led the research. Results were published online in JAMA Network Open.

In addition, 29% of survey respondents turned down career advancement opportunities; 21% chose a different specialty; and 17% changed from an academic to private practice setting to accommodate having children.

Women in the survey cited as factors in their decisions lack of support from physician peers and leadership, particularly around time off for pregnancy, maternity leave, infertility treatments, or parental responsibilities.
 

Results ‘alarming’

“These results are alarming, particularly in light of known gender disparities that exist within academic medicine in time to promotion, achievement of academic rank, and appointment to leadership positions,” the authors wrote.

As of 2020, women made up 43% of medical school faculty but only 21% of department chairs and 19% of medical school deans, according to Association of American Medical Colleges data.

Navigating motherhood as a physician also can take a physical and mental toll. Recent data presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 annual meeting found that one in four physicians who are new mothers report struggling with postpartum depression, a rate twice that of the general population.

And one in four women in a recent survey of 600 female physicians who had attempted conception were diagnosed with infertility.
 

Lack of support ‘pronounced in medicine’

In an invited commentary, Ariela L. Marshall, MD, of the division of hematology-oncology at University of Pennsylvania, Philadelphia, and Arghavan Salles, MD, PhD, of the department of medicine at Stanford (Calif.) University, noted that career-family struggle is not unique to medicine but “the lack of support for pregnancy is particularly pronounced in medicine.”

The editorialists wrote that they have battled infertility and faced family-building challenges and have intimate familiarity with the struggles.

“Although other workplaces, such as Microsoft, Google, and Facebook, long ago adopted policies to support employees’ family building, including via cryopreservation, those in medicine all too frequently must pay back their parental leave, make up missed call, or even pay back money to their practice,” they wrote. “It is embarrassing that employees of tech companies have better support for reproductive health than do physicians.”

They advocate for change on the entire continuum from fertility awareness and infertility management, bringing children into a family by any method, and child care and career development support for physicians who become parents.

They urge establishing adequate paid parental leave, not just for parents who give birth but for all parents involved in rearing children. They say providing leave to only one parent sets up a discriminatory divide between the partner who continues to work and the person providing care.

Dr. Marshall and Dr. Salles wrote that lack of support is likely part of the reason that 40% of women in medicine switch to part-time positions within their first 6 years in practice.

They also note that too often fertility and family-building discussions focus on cisgendered women who are in heterosexual relationships.

They cite some “nonsensical“ policies around insurance. They give an example of coverage for fertility treatments that often requires trying to conceive before benefits are provided.

“How do two women, two men, or a single person try to conceive?” they ask.

Helen Kang Morgan, MD, clinical professor of obstetrics and gynecology at the University of Michigan, Ann Arbor, said that she, too, has made the trade-off the researchers describe.

She was in her first year as a faculty physician at the University of Michigan when she became a mom and decided to go part time.

Unlike some of the women interviewed in the Smith et al. study, she said she felt lucky to have peer support and the support of leaders in her department who made sure she wasn’t derailed from her career path because she chose part-time work for nearly 5 years.

“For some women, part-time is the right choice and for me, at the time, it was the right choice, but it should not be the only choice. It makes it so much harder for women to advance their careers if part-time is the only option,” she said.

Dr. Morgan said this work highlights that conversations about work and parenting needs in medicine have to go from informal conversations to formal conversations.

Department leaders should be asking what female physicians need and what flexibility is needed, she said.

The COVID-19 pandemic showed how bad things could get, she said.

In Ann Arbor, Dr. Morgan noted, schools were virtual until the spring of 2021, putting demands disproportionately on female physicians who absorbed much of the at-home child care responsibilities.

“That created gender inequities I think it is going to take women many, many years to catch up from,” she said.

COVID-19 also, however, forced medicine to incorporate more virtual options, something that should stay in finding solutions to ease the burden on physicians who are mothers, she said.

Reshma Jagsi, MD, deputy chair in the department of radiation oncology at the University of Michigan, said both policies and cultural norms need to change in medicine.

Courtesy Michigan Medicine

Qualitative interviews with a group of female physicians identified several concerns about fertility and family planning and how those concerns affected their career choices.

Among the findings in a new study were that all 16 women interviewed said medical school education surrounding fertility was inadequate. Many said students should get comprehensive information about fertility’s decline with age and fertility preservation options and that information should be presented early in medical training so students can make choices. Yet, such issues are rarely discussed as part of medical training.

“[I]t would also be helpful for medical students and trainees to know what their options are, what insurance covers ... It wasn’t even touched at my orientation,” said one participant.

The findings from the hour-long interviews were used to build a survey. In a pilot test of the survey on 24 female physicians, researchers found that 71% had delayed childbearing and 67% had altered their careers to build families.

Kathryn S. Smith of Northwestern University, Chicago, led the research. Results were published online in JAMA Network Open.

In addition, 29% of survey respondents turned down career advancement opportunities; 21% chose a different specialty; and 17% changed from an academic to private practice setting to accommodate having children.

Women in the survey cited as factors in their decisions lack of support from physician peers and leadership, particularly around time off for pregnancy, maternity leave, infertility treatments, or parental responsibilities.
 

Results ‘alarming’

“These results are alarming, particularly in light of known gender disparities that exist within academic medicine in time to promotion, achievement of academic rank, and appointment to leadership positions,” the authors wrote.

As of 2020, women made up 43% of medical school faculty but only 21% of department chairs and 19% of medical school deans, according to Association of American Medical Colleges data.

Navigating motherhood as a physician also can take a physical and mental toll. Recent data presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 annual meeting found that one in four physicians who are new mothers report struggling with postpartum depression, a rate twice that of the general population.

And one in four women in a recent survey of 600 female physicians who had attempted conception were diagnosed with infertility.
 

Lack of support ‘pronounced in medicine’

In an invited commentary, Ariela L. Marshall, MD, of the division of hematology-oncology at University of Pennsylvania, Philadelphia, and Arghavan Salles, MD, PhD, of the department of medicine at Stanford (Calif.) University, noted that career-family struggle is not unique to medicine but “the lack of support for pregnancy is particularly pronounced in medicine.”

The editorialists wrote that they have battled infertility and faced family-building challenges and have intimate familiarity with the struggles.

“Although other workplaces, such as Microsoft, Google, and Facebook, long ago adopted policies to support employees’ family building, including via cryopreservation, those in medicine all too frequently must pay back their parental leave, make up missed call, or even pay back money to their practice,” they wrote. “It is embarrassing that employees of tech companies have better support for reproductive health than do physicians.”

They advocate for change on the entire continuum from fertility awareness and infertility management, bringing children into a family by any method, and child care and career development support for physicians who become parents.

They urge establishing adequate paid parental leave, not just for parents who give birth but for all parents involved in rearing children. They say providing leave to only one parent sets up a discriminatory divide between the partner who continues to work and the person providing care.

Dr. Marshall and Dr. Salles wrote that lack of support is likely part of the reason that 40% of women in medicine switch to part-time positions within their first 6 years in practice.

They also note that too often fertility and family-building discussions focus on cisgendered women who are in heterosexual relationships.

They cite some “nonsensical“ policies around insurance. They give an example of coverage for fertility treatments that often requires trying to conceive before benefits are provided.

“How do two women, two men, or a single person try to conceive?” they ask.

Helen Kang Morgan, MD, clinical professor of obstetrics and gynecology at the University of Michigan, Ann Arbor, said that she, too, has made the trade-off the researchers describe.

She was in her first year as a faculty physician at the University of Michigan when she became a mom and decided to go part time.

Unlike some of the women interviewed in the Smith et al. study, she said she felt lucky to have peer support and the support of leaders in her department who made sure she wasn’t derailed from her career path because she chose part-time work for nearly 5 years.

“For some women, part-time is the right choice and for me, at the time, it was the right choice, but it should not be the only choice. It makes it so much harder for women to advance their careers if part-time is the only option,” she said.

Dr. Morgan said this work highlights that conversations about work and parenting needs in medicine have to go from informal conversations to formal conversations.

Department leaders should be asking what female physicians need and what flexibility is needed, she said.

The COVID-19 pandemic showed how bad things could get, she said.

In Ann Arbor, Dr. Morgan noted, schools were virtual until the spring of 2021, putting demands disproportionately on female physicians who absorbed much of the at-home child care responsibilities.

“That created gender inequities I think it is going to take women many, many years to catch up from,” she said.

COVID-19 also, however, forced medicine to incorporate more virtual options, something that should stay in finding solutions to ease the burden on physicians who are mothers, she said.

Reshma Jagsi, MD, deputy chair in the department of radiation oncology at the University of Michigan, said both policies and cultural norms need to change in medicine.

Courtesy Michigan Medicine

Qualitative interviews with a group of female physicians identified several concerns about fertility and family planning and how those concerns affected their career choices.

Among the findings in a new study were that all 16 women interviewed said medical school education surrounding fertility was inadequate. Many said students should get comprehensive information about fertility’s decline with age and fertility preservation options and that information should be presented early in medical training so students can make choices. Yet, such issues are rarely discussed as part of medical training.

“[I]t would also be helpful for medical students and trainees to know what their options are, what insurance covers ... It wasn’t even touched at my orientation,” said one participant.

The findings from the hour-long interviews were used to build a survey. In a pilot test of the survey on 24 female physicians, researchers found that 71% had delayed childbearing and 67% had altered their careers to build families.

Kathryn S. Smith of Northwestern University, Chicago, led the research. Results were published online in JAMA Network Open.

In addition, 29% of survey respondents turned down career advancement opportunities; 21% chose a different specialty; and 17% changed from an academic to private practice setting to accommodate having children.

Women in the survey cited as factors in their decisions lack of support from physician peers and leadership, particularly around time off for pregnancy, maternity leave, infertility treatments, or parental responsibilities.
 

Results ‘alarming’

“These results are alarming, particularly in light of known gender disparities that exist within academic medicine in time to promotion, achievement of academic rank, and appointment to leadership positions,” the authors wrote.

As of 2020, women made up 43% of medical school faculty but only 21% of department chairs and 19% of medical school deans, according to Association of American Medical Colleges data.

Navigating motherhood as a physician also can take a physical and mental toll. Recent data presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 annual meeting found that one in four physicians who are new mothers report struggling with postpartum depression, a rate twice that of the general population.

And one in four women in a recent survey of 600 female physicians who had attempted conception were diagnosed with infertility.
 

Lack of support ‘pronounced in medicine’

In an invited commentary, Ariela L. Marshall, MD, of the division of hematology-oncology at University of Pennsylvania, Philadelphia, and Arghavan Salles, MD, PhD, of the department of medicine at Stanford (Calif.) University, noted that career-family struggle is not unique to medicine but “the lack of support for pregnancy is particularly pronounced in medicine.”

The editorialists wrote that they have battled infertility and faced family-building challenges and have intimate familiarity with the struggles.

“Although other workplaces, such as Microsoft, Google, and Facebook, long ago adopted policies to support employees’ family building, including via cryopreservation, those in medicine all too frequently must pay back their parental leave, make up missed call, or even pay back money to their practice,” they wrote. “It is embarrassing that employees of tech companies have better support for reproductive health than do physicians.”

They advocate for change on the entire continuum from fertility awareness and infertility management, bringing children into a family by any method, and child care and career development support for physicians who become parents.

They urge establishing adequate paid parental leave, not just for parents who give birth but for all parents involved in rearing children. They say providing leave to only one parent sets up a discriminatory divide between the partner who continues to work and the person providing care.

Dr. Marshall and Dr. Salles wrote that lack of support is likely part of the reason that 40% of women in medicine switch to part-time positions within their first 6 years in practice.

They also note that too often fertility and family-building discussions focus on cisgendered women who are in heterosexual relationships.

They cite some “nonsensical“ policies around insurance. They give an example of coverage for fertility treatments that often requires trying to conceive before benefits are provided.

“How do two women, two men, or a single person try to conceive?” they ask.

Helen Kang Morgan, MD, clinical professor of obstetrics and gynecology at the University of Michigan, Ann Arbor, said that she, too, has made the trade-off the researchers describe.

She was in her first year as a faculty physician at the University of Michigan when she became a mom and decided to go part time.

Unlike some of the women interviewed in the Smith et al. study, she said she felt lucky to have peer support and the support of leaders in her department who made sure she wasn’t derailed from her career path because she chose part-time work for nearly 5 years.

“For some women, part-time is the right choice and for me, at the time, it was the right choice, but it should not be the only choice. It makes it so much harder for women to advance their careers if part-time is the only option,” she said.

Dr. Morgan said this work highlights that conversations about work and parenting needs in medicine have to go from informal conversations to formal conversations.

Department leaders should be asking what female physicians need and what flexibility is needed, she said.

The COVID-19 pandemic showed how bad things could get, she said.

In Ann Arbor, Dr. Morgan noted, schools were virtual until the spring of 2021, putting demands disproportionately on female physicians who absorbed much of the at-home child care responsibilities.

“That created gender inequities I think it is going to take women many, many years to catch up from,” she said.

COVID-19 also, however, forced medicine to incorporate more virtual options, something that should stay in finding solutions to ease the burden on physicians who are mothers, she said.

Reshma Jagsi, MD, deputy chair in the department of radiation oncology at the University of Michigan, said both policies and cultural norms need to change in medicine.

Courtesy Michigan Medicine

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

A version of this article first appeared on Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

A version of this article first appeared on Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

A version of this article first appeared on Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.