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Diabetes decision tool yields ‘modest’ benefit in low-resource clinics
a randomized trial in China showed.
The tool required clinicians to enter patient data into a computer in order to generate individualized treatment recommendations, adding to their administrative burdens. It also couldn’t tackle patients’ problems with access and affordability of medications.
Nevertheless, the model could curtail physician burnout and improve the quality of care in primary care clinics with limited resources, the researchers said in a paper published in the Annals of Internal Medicine.
They concluded that the findings support “widespread adoption” of the model in China and other low- or middle-income countries where diabetes is on the rise.
Co–principal investigator Jiang He, MD, PhD, chair of epidemiology at Tulane University, New Orleans, said the findings could apply to federally qualified health care (FQHC) clinics that treat underserved patients in the United States.
“At many FQHC clinics, nurse practitioners have to take care of patients with multiple chronic disease conditions. Team-based care with a computerized clinical decision support system will help them and improve patient care,” Dr. He said.
Small improvements
To conduct the trial, called Diabetes Complication Control in Community Clinics (D4C), Dr. He and colleagues randomly assigned 19 out of the 38 community health centers in Xiamen, China, to have a clinical decision support tool installed on the computers of primary care physicians and health coaches.
Starting in October 2016 the researchers recruited 11,132 patients aged 50 and older with uncontrolled diabetes and at least one comorbid condition, with 5,475 patients receiving team-based care with the CDSS and the remainder receiving team-based care alone.
The CDSS generated individualized risk factor summaries and treatment recommendations, including prescriptions based on Chinese and U.S. clinical guidelines. It incorporated data on patients’ insurance plans and local availability of drugs.
At all centers, primary care physicians received training in managing glycemia, blood pressure, and lipids. Nurses were certified as health coaches after receiving training on nutrition, lifestyle changes, and medication adherence. Patients met with their coaches for half an hour every 3 months, and diabetes specialists visited each clinic monthly for team meetings and consultations.
After 18 months, patients undergoing team-based care alone lowered their hemoglobin A1c by 0.6 percentage points (95% confidence interval, –0.7 to –0.5 percentage points), LDL cholesterol by 12.5 mg/dL (95% CI, –13.6 to –11.3 mg/dL), and systolic blood pressure by 7.5 mm Hg (95% CI, –8.4 to –6.6 mm Hg).
The group whose care teams used the CDSS further reduced A1c by 0.2 percentage points (95% CI, –0.3 to –0.1 percentage points), LDL cholesterol by 6.5 mg/dL (95% CI, –8.3 to -4.6 mg/dL), and blood pressure by 1.5 mm Hg (95% CI, –2.8 to –0.3 mm Hg).
All-cause mortality did not differ between the groups. Serious adverse events occurred in 9.1% of the CDSS group, compared with 10.9% of the group whose care team did not use the CDSS.
Addressing social needs
Experts who were not involved in the trial said the marginal impact of the CDSS was no surprise given the mixed results of such tools in previous studies.
However, the lackluster result “might be a shock to people investing a lot in clinical decision support,” said Elbert Huang, MD, MPH, director of the Center for Chronic Disease Research and Policy at the University of Chicago.
Anne Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, said the administrative burden of entering each patient’s data into the system would slow down care and frustrate clinicians. “The system has to be smarter than this.”
On the other hand, the findings of the D4C trial align with other research showing that team-based care strategies are effective for diabetes management.
Dr. Huang noted that there is a “well-established history” of diabetes quality improvement programs, health coaches, buddy programs, and community health worker programs. He added that the new findings “might help to remind everyone of the importance of these programs, which are not always well supported.”
“The bottom line of the paper might be that investing in patient engagement programs might get us 90% of the way to our goal of improving diabetes care,” Dr. Huang said.
Still, Dr. Peters said the portion of patients in the trial who benefited from team-based care seemed “disturbingly low.” Just 16.9% of patients who received team-based care and CDSS and 13% of those who received team-based care alone improved in all three measures. “This system doesn’t get you to where you want to be by a long shot.”
She added that a team-based approach, particularly the use of health coaches, would be a “huge improvement” over fragmented care provided in much of the U.S. safety-net system.
Another team approach
Many systems are striving to improve diabetes management in response to payment incentives, Dr. Huang said.
In a separate retrospective analysis, published in Annals of Family Medicine, researchers at the Mayo Clinic, Rochester, Minn., reported quality improvement gains among primary care practices that adopted a team-based model called Enhanced Primary Care Diabetes (EPCD). The model deployed a range of strategies, such as empowering nurses to engage with patients outside of scheduled office visits and including pharmacists on care teams.
Mayo’s approach did not specifically target underserved populations. Rather, researchers evaluated the model’s impact on about 17,000 patients treated at 32 Mayo internal medicine and family medicine practices of varying sizes, resources, and community settings.
Among staff clinician practices using the EPCD model improved patients’ scores on a composite quality measure called D5, which incorporates glycemic control, blood pressure control, low-density lipoprotein control, tobacco abstinence, and aspirin use.
Following implementation, the portion of patients in those practices meeting the D5 indicator increased from 42.9% to 45.0% (incident rate ratio, 1.005; P = .001).
Meanwhile, the portion of patients meeting the indicator increased from 38.9% to 42.0% (IRR, 1.011; P = .003) at resident physician practices that used the EPCD model and decreased from 36.2% to 35.5% (IRR, 0.994; P < .001) at staff clinician practices that did not use the model.
In contrast to the team-based approach used in China, the EPCD protocol “is very complex, and it will be difficult to implement in low-resource settings,” Dr. He said.
The D4C trial was funded by the Xiamen Municipal Health Commission. The Mayo study was funded by a National Institutes of Diabetes and Digestive and Kidney Diseases grant. Dr. He, Dr. Peters, and Dr. Huang reported no relevant financial interests.
a randomized trial in China showed.
The tool required clinicians to enter patient data into a computer in order to generate individualized treatment recommendations, adding to their administrative burdens. It also couldn’t tackle patients’ problems with access and affordability of medications.
Nevertheless, the model could curtail physician burnout and improve the quality of care in primary care clinics with limited resources, the researchers said in a paper published in the Annals of Internal Medicine.
They concluded that the findings support “widespread adoption” of the model in China and other low- or middle-income countries where diabetes is on the rise.
Co–principal investigator Jiang He, MD, PhD, chair of epidemiology at Tulane University, New Orleans, said the findings could apply to federally qualified health care (FQHC) clinics that treat underserved patients in the United States.
“At many FQHC clinics, nurse practitioners have to take care of patients with multiple chronic disease conditions. Team-based care with a computerized clinical decision support system will help them and improve patient care,” Dr. He said.
Small improvements
To conduct the trial, called Diabetes Complication Control in Community Clinics (D4C), Dr. He and colleagues randomly assigned 19 out of the 38 community health centers in Xiamen, China, to have a clinical decision support tool installed on the computers of primary care physicians and health coaches.
Starting in October 2016 the researchers recruited 11,132 patients aged 50 and older with uncontrolled diabetes and at least one comorbid condition, with 5,475 patients receiving team-based care with the CDSS and the remainder receiving team-based care alone.
The CDSS generated individualized risk factor summaries and treatment recommendations, including prescriptions based on Chinese and U.S. clinical guidelines. It incorporated data on patients’ insurance plans and local availability of drugs.
At all centers, primary care physicians received training in managing glycemia, blood pressure, and lipids. Nurses were certified as health coaches after receiving training on nutrition, lifestyle changes, and medication adherence. Patients met with their coaches for half an hour every 3 months, and diabetes specialists visited each clinic monthly for team meetings and consultations.
After 18 months, patients undergoing team-based care alone lowered their hemoglobin A1c by 0.6 percentage points (95% confidence interval, –0.7 to –0.5 percentage points), LDL cholesterol by 12.5 mg/dL (95% CI, –13.6 to –11.3 mg/dL), and systolic blood pressure by 7.5 mm Hg (95% CI, –8.4 to –6.6 mm Hg).
The group whose care teams used the CDSS further reduced A1c by 0.2 percentage points (95% CI, –0.3 to –0.1 percentage points), LDL cholesterol by 6.5 mg/dL (95% CI, –8.3 to -4.6 mg/dL), and blood pressure by 1.5 mm Hg (95% CI, –2.8 to –0.3 mm Hg).
All-cause mortality did not differ between the groups. Serious adverse events occurred in 9.1% of the CDSS group, compared with 10.9% of the group whose care team did not use the CDSS.
Addressing social needs
Experts who were not involved in the trial said the marginal impact of the CDSS was no surprise given the mixed results of such tools in previous studies.
However, the lackluster result “might be a shock to people investing a lot in clinical decision support,” said Elbert Huang, MD, MPH, director of the Center for Chronic Disease Research and Policy at the University of Chicago.
Anne Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, said the administrative burden of entering each patient’s data into the system would slow down care and frustrate clinicians. “The system has to be smarter than this.”
On the other hand, the findings of the D4C trial align with other research showing that team-based care strategies are effective for diabetes management.
Dr. Huang noted that there is a “well-established history” of diabetes quality improvement programs, health coaches, buddy programs, and community health worker programs. He added that the new findings “might help to remind everyone of the importance of these programs, which are not always well supported.”
“The bottom line of the paper might be that investing in patient engagement programs might get us 90% of the way to our goal of improving diabetes care,” Dr. Huang said.
Still, Dr. Peters said the portion of patients in the trial who benefited from team-based care seemed “disturbingly low.” Just 16.9% of patients who received team-based care and CDSS and 13% of those who received team-based care alone improved in all three measures. “This system doesn’t get you to where you want to be by a long shot.”
She added that a team-based approach, particularly the use of health coaches, would be a “huge improvement” over fragmented care provided in much of the U.S. safety-net system.
Another team approach
Many systems are striving to improve diabetes management in response to payment incentives, Dr. Huang said.
In a separate retrospective analysis, published in Annals of Family Medicine, researchers at the Mayo Clinic, Rochester, Minn., reported quality improvement gains among primary care practices that adopted a team-based model called Enhanced Primary Care Diabetes (EPCD). The model deployed a range of strategies, such as empowering nurses to engage with patients outside of scheduled office visits and including pharmacists on care teams.
Mayo’s approach did not specifically target underserved populations. Rather, researchers evaluated the model’s impact on about 17,000 patients treated at 32 Mayo internal medicine and family medicine practices of varying sizes, resources, and community settings.
Among staff clinician practices using the EPCD model improved patients’ scores on a composite quality measure called D5, which incorporates glycemic control, blood pressure control, low-density lipoprotein control, tobacco abstinence, and aspirin use.
Following implementation, the portion of patients in those practices meeting the D5 indicator increased from 42.9% to 45.0% (incident rate ratio, 1.005; P = .001).
Meanwhile, the portion of patients meeting the indicator increased from 38.9% to 42.0% (IRR, 1.011; P = .003) at resident physician practices that used the EPCD model and decreased from 36.2% to 35.5% (IRR, 0.994; P < .001) at staff clinician practices that did not use the model.
In contrast to the team-based approach used in China, the EPCD protocol “is very complex, and it will be difficult to implement in low-resource settings,” Dr. He said.
The D4C trial was funded by the Xiamen Municipal Health Commission. The Mayo study was funded by a National Institutes of Diabetes and Digestive and Kidney Diseases grant. Dr. He, Dr. Peters, and Dr. Huang reported no relevant financial interests.
a randomized trial in China showed.
The tool required clinicians to enter patient data into a computer in order to generate individualized treatment recommendations, adding to their administrative burdens. It also couldn’t tackle patients’ problems with access and affordability of medications.
Nevertheless, the model could curtail physician burnout and improve the quality of care in primary care clinics with limited resources, the researchers said in a paper published in the Annals of Internal Medicine.
They concluded that the findings support “widespread adoption” of the model in China and other low- or middle-income countries where diabetes is on the rise.
Co–principal investigator Jiang He, MD, PhD, chair of epidemiology at Tulane University, New Orleans, said the findings could apply to federally qualified health care (FQHC) clinics that treat underserved patients in the United States.
“At many FQHC clinics, nurse practitioners have to take care of patients with multiple chronic disease conditions. Team-based care with a computerized clinical decision support system will help them and improve patient care,” Dr. He said.
Small improvements
To conduct the trial, called Diabetes Complication Control in Community Clinics (D4C), Dr. He and colleagues randomly assigned 19 out of the 38 community health centers in Xiamen, China, to have a clinical decision support tool installed on the computers of primary care physicians and health coaches.
Starting in October 2016 the researchers recruited 11,132 patients aged 50 and older with uncontrolled diabetes and at least one comorbid condition, with 5,475 patients receiving team-based care with the CDSS and the remainder receiving team-based care alone.
The CDSS generated individualized risk factor summaries and treatment recommendations, including prescriptions based on Chinese and U.S. clinical guidelines. It incorporated data on patients’ insurance plans and local availability of drugs.
At all centers, primary care physicians received training in managing glycemia, blood pressure, and lipids. Nurses were certified as health coaches after receiving training on nutrition, lifestyle changes, and medication adherence. Patients met with their coaches for half an hour every 3 months, and diabetes specialists visited each clinic monthly for team meetings and consultations.
After 18 months, patients undergoing team-based care alone lowered their hemoglobin A1c by 0.6 percentage points (95% confidence interval, –0.7 to –0.5 percentage points), LDL cholesterol by 12.5 mg/dL (95% CI, –13.6 to –11.3 mg/dL), and systolic blood pressure by 7.5 mm Hg (95% CI, –8.4 to –6.6 mm Hg).
The group whose care teams used the CDSS further reduced A1c by 0.2 percentage points (95% CI, –0.3 to –0.1 percentage points), LDL cholesterol by 6.5 mg/dL (95% CI, –8.3 to -4.6 mg/dL), and blood pressure by 1.5 mm Hg (95% CI, –2.8 to –0.3 mm Hg).
All-cause mortality did not differ between the groups. Serious adverse events occurred in 9.1% of the CDSS group, compared with 10.9% of the group whose care team did not use the CDSS.
Addressing social needs
Experts who were not involved in the trial said the marginal impact of the CDSS was no surprise given the mixed results of such tools in previous studies.
However, the lackluster result “might be a shock to people investing a lot in clinical decision support,” said Elbert Huang, MD, MPH, director of the Center for Chronic Disease Research and Policy at the University of Chicago.
Anne Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, said the administrative burden of entering each patient’s data into the system would slow down care and frustrate clinicians. “The system has to be smarter than this.”
On the other hand, the findings of the D4C trial align with other research showing that team-based care strategies are effective for diabetes management.
Dr. Huang noted that there is a “well-established history” of diabetes quality improvement programs, health coaches, buddy programs, and community health worker programs. He added that the new findings “might help to remind everyone of the importance of these programs, which are not always well supported.”
“The bottom line of the paper might be that investing in patient engagement programs might get us 90% of the way to our goal of improving diabetes care,” Dr. Huang said.
Still, Dr. Peters said the portion of patients in the trial who benefited from team-based care seemed “disturbingly low.” Just 16.9% of patients who received team-based care and CDSS and 13% of those who received team-based care alone improved in all three measures. “This system doesn’t get you to where you want to be by a long shot.”
She added that a team-based approach, particularly the use of health coaches, would be a “huge improvement” over fragmented care provided in much of the U.S. safety-net system.
Another team approach
Many systems are striving to improve diabetes management in response to payment incentives, Dr. Huang said.
In a separate retrospective analysis, published in Annals of Family Medicine, researchers at the Mayo Clinic, Rochester, Minn., reported quality improvement gains among primary care practices that adopted a team-based model called Enhanced Primary Care Diabetes (EPCD). The model deployed a range of strategies, such as empowering nurses to engage with patients outside of scheduled office visits and including pharmacists on care teams.
Mayo’s approach did not specifically target underserved populations. Rather, researchers evaluated the model’s impact on about 17,000 patients treated at 32 Mayo internal medicine and family medicine practices of varying sizes, resources, and community settings.
Among staff clinician practices using the EPCD model improved patients’ scores on a composite quality measure called D5, which incorporates glycemic control, blood pressure control, low-density lipoprotein control, tobacco abstinence, and aspirin use.
Following implementation, the portion of patients in those practices meeting the D5 indicator increased from 42.9% to 45.0% (incident rate ratio, 1.005; P = .001).
Meanwhile, the portion of patients meeting the indicator increased from 38.9% to 42.0% (IRR, 1.011; P = .003) at resident physician practices that used the EPCD model and decreased from 36.2% to 35.5% (IRR, 0.994; P < .001) at staff clinician practices that did not use the model.
In contrast to the team-based approach used in China, the EPCD protocol “is very complex, and it will be difficult to implement in low-resource settings,” Dr. He said.
The D4C trial was funded by the Xiamen Municipal Health Commission. The Mayo study was funded by a National Institutes of Diabetes and Digestive and Kidney Diseases grant. Dr. He, Dr. Peters, and Dr. Huang reported no relevant financial interests.
FROM ANNALS OF INTERNAL MEDICINE
AAP issues guidelines to combat rise in respiratory illness
Updated guidance from the group outlines measures to optimize resources to manage a surge of patients filling hospital beds, emergency departments, and physicians’ practices.
A separate document from the AAP endorses giving extra doses of palivizumab, a monoclonal antibody used to prevent severe infection in infants at high risk of respiratory syncytial virus (RSV), as long as the illness is prevalent in the community.
Upticks in rates of RSV and influenza, along with a crisis in children’s mental health, prompted the AAP and the Children’s Hospital Association to petition the Biden administration on Nov. 14 to declare an emergency. Such a move would free up extra funding and waivers to allow physicians and hospitals to pool resources, the organizations said.
Despite those challenges, the AAP stressed in its new guidance that routine care, such as immunizations and chronic disease management, “cannot be neglected.”
Shifting resources
Officials at some children’s hospitals said that they have already implemented many of the AAP’s recommended measures for providing care during a surge, such as cross-training staff who usually treat adults, expanding telehealth and urgent care, and optimizing the use of ancillary care spaces.
“A lot of this is just reinforcing the things that I think children’s hospitals have been doing,” Lindsay Ragsdale, MD, chief medical officer for Kentucky Children’s Hospital, Lexington, said. “Can we shift adults around? Can we use an adult unit? Can we use an occupied space creatively? We’re really thinking outside the box.”
Andrew Pavia, MD, chief of the division of pediatric infectious diseases at University of Utah Health, Salt Lake City, said large children’s hospitals have been actively sharing practices for handling a surge through various channels, but the new guidance could be a useful “checklist” for small hospitals and physician practices that lack well-developed plans.
The AAP’s suggestions for pediatricians in outpatient settings include stocking up on personal protective equipment, using social media and office staff to increase communication with families, and keeping abreast of wait times at local emergency departments.
Addressing a subset of kids
In updated guidance for palivizumab, the AAP noted that earlier-than-usual circulation of RSV prompted pediatricians in some areas to begin administering the drug in the summer and early fall.
Palivizumab is typically given in five consecutive monthly intramuscular injections during RSV season, starting in November. Eligible infants and young children include those born prematurely or who have conditions such as chronic lung disease, hemodynamically significant congenital heart disease, or a suppressed immune system.
The AAP said it supports giving extra doses if RSV activity “persists at high levels in a given region through the fall and winter.” Published studies are sparse but contain “no evidence of increased frequency or severity of adverse events with later doses in a five-dose series nor with doses beyond five doses,” the group added.
The guidance may encourage payers to pick up the tab for extra doses, which are priced at more than $1,800 for cash customers, Dr. Pavia said. However, that recommendation addresses “a pretty small part of the problem overall because the injections are used for a very small subset of kids who are at the highest risk, and more than 80% of hospitalizations for RSV are among healthy kids,” he added.
Dr. Ragsdale and Dr. Pavia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Updated guidance from the group outlines measures to optimize resources to manage a surge of patients filling hospital beds, emergency departments, and physicians’ practices.
A separate document from the AAP endorses giving extra doses of palivizumab, a monoclonal antibody used to prevent severe infection in infants at high risk of respiratory syncytial virus (RSV), as long as the illness is prevalent in the community.
Upticks in rates of RSV and influenza, along with a crisis in children’s mental health, prompted the AAP and the Children’s Hospital Association to petition the Biden administration on Nov. 14 to declare an emergency. Such a move would free up extra funding and waivers to allow physicians and hospitals to pool resources, the organizations said.
Despite those challenges, the AAP stressed in its new guidance that routine care, such as immunizations and chronic disease management, “cannot be neglected.”
Shifting resources
Officials at some children’s hospitals said that they have already implemented many of the AAP’s recommended measures for providing care during a surge, such as cross-training staff who usually treat adults, expanding telehealth and urgent care, and optimizing the use of ancillary care spaces.
“A lot of this is just reinforcing the things that I think children’s hospitals have been doing,” Lindsay Ragsdale, MD, chief medical officer for Kentucky Children’s Hospital, Lexington, said. “Can we shift adults around? Can we use an adult unit? Can we use an occupied space creatively? We’re really thinking outside the box.”
Andrew Pavia, MD, chief of the division of pediatric infectious diseases at University of Utah Health, Salt Lake City, said large children’s hospitals have been actively sharing practices for handling a surge through various channels, but the new guidance could be a useful “checklist” for small hospitals and physician practices that lack well-developed plans.
The AAP’s suggestions for pediatricians in outpatient settings include stocking up on personal protective equipment, using social media and office staff to increase communication with families, and keeping abreast of wait times at local emergency departments.
Addressing a subset of kids
In updated guidance for palivizumab, the AAP noted that earlier-than-usual circulation of RSV prompted pediatricians in some areas to begin administering the drug in the summer and early fall.
Palivizumab is typically given in five consecutive monthly intramuscular injections during RSV season, starting in November. Eligible infants and young children include those born prematurely or who have conditions such as chronic lung disease, hemodynamically significant congenital heart disease, or a suppressed immune system.
The AAP said it supports giving extra doses if RSV activity “persists at high levels in a given region through the fall and winter.” Published studies are sparse but contain “no evidence of increased frequency or severity of adverse events with later doses in a five-dose series nor with doses beyond five doses,” the group added.
The guidance may encourage payers to pick up the tab for extra doses, which are priced at more than $1,800 for cash customers, Dr. Pavia said. However, that recommendation addresses “a pretty small part of the problem overall because the injections are used for a very small subset of kids who are at the highest risk, and more than 80% of hospitalizations for RSV are among healthy kids,” he added.
Dr. Ragsdale and Dr. Pavia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Updated guidance from the group outlines measures to optimize resources to manage a surge of patients filling hospital beds, emergency departments, and physicians’ practices.
A separate document from the AAP endorses giving extra doses of palivizumab, a monoclonal antibody used to prevent severe infection in infants at high risk of respiratory syncytial virus (RSV), as long as the illness is prevalent in the community.
Upticks in rates of RSV and influenza, along with a crisis in children’s mental health, prompted the AAP and the Children’s Hospital Association to petition the Biden administration on Nov. 14 to declare an emergency. Such a move would free up extra funding and waivers to allow physicians and hospitals to pool resources, the organizations said.
Despite those challenges, the AAP stressed in its new guidance that routine care, such as immunizations and chronic disease management, “cannot be neglected.”
Shifting resources
Officials at some children’s hospitals said that they have already implemented many of the AAP’s recommended measures for providing care during a surge, such as cross-training staff who usually treat adults, expanding telehealth and urgent care, and optimizing the use of ancillary care spaces.
“A lot of this is just reinforcing the things that I think children’s hospitals have been doing,” Lindsay Ragsdale, MD, chief medical officer for Kentucky Children’s Hospital, Lexington, said. “Can we shift adults around? Can we use an adult unit? Can we use an occupied space creatively? We’re really thinking outside the box.”
Andrew Pavia, MD, chief of the division of pediatric infectious diseases at University of Utah Health, Salt Lake City, said large children’s hospitals have been actively sharing practices for handling a surge through various channels, but the new guidance could be a useful “checklist” for small hospitals and physician practices that lack well-developed plans.
The AAP’s suggestions for pediatricians in outpatient settings include stocking up on personal protective equipment, using social media and office staff to increase communication with families, and keeping abreast of wait times at local emergency departments.
Addressing a subset of kids
In updated guidance for palivizumab, the AAP noted that earlier-than-usual circulation of RSV prompted pediatricians in some areas to begin administering the drug in the summer and early fall.
Palivizumab is typically given in five consecutive monthly intramuscular injections during RSV season, starting in November. Eligible infants and young children include those born prematurely or who have conditions such as chronic lung disease, hemodynamically significant congenital heart disease, or a suppressed immune system.
The AAP said it supports giving extra doses if RSV activity “persists at high levels in a given region through the fall and winter.” Published studies are sparse but contain “no evidence of increased frequency or severity of adverse events with later doses in a five-dose series nor with doses beyond five doses,” the group added.
The guidance may encourage payers to pick up the tab for extra doses, which are priced at more than $1,800 for cash customers, Dr. Pavia said. However, that recommendation addresses “a pretty small part of the problem overall because the injections are used for a very small subset of kids who are at the highest risk, and more than 80% of hospitalizations for RSV are among healthy kids,” he added.
Dr. Ragsdale and Dr. Pavia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Analysis affirms that giving birth protects against endometrial cancer
Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.
In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.
Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.
The researcher published their findings in BMC Medicine.
Leverage genetic data
The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.
Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.
The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.
A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.
Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.
In addition, the genetic data came exclusively from White women of European ancestry.
‘A personal choice’
Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.
Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.
However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”
“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.
The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.
Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.
In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.
Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.
The researcher published their findings in BMC Medicine.
Leverage genetic data
The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.
Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.
The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.
A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.
Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.
In addition, the genetic data came exclusively from White women of European ancestry.
‘A personal choice’
Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.
Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.
However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”
“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.
The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.
Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.
In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.
Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.
The researcher published their findings in BMC Medicine.
Leverage genetic data
The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.
Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.
The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.
A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.
Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.
In addition, the genetic data came exclusively from White women of European ancestry.
‘A personal choice’
Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.
Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.
However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”
“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.
The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.
FROM BMC MEDICINE
Does subclinical hyperthyroidism raise fracture risk?
People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.
The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.
Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.
Ms. Daya and her colleagues published their findings in JAMA Network Open.
Building on earlier findings
The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.
“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.
The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.
Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.
Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.
The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.
Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.
Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.
Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.
Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
‘An important risk factor’
Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.
The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.
Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.
However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.
The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.
“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.
The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.
The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.
Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.
Ms. Daya and her colleagues published their findings in JAMA Network Open.
Building on earlier findings
The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.
“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.
The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.
Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.
Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.
The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.
Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.
Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.
Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.
Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
‘An important risk factor’
Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.
The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.
Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.
However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.
The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.
“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.
The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.
The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.
Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.
Ms. Daya and her colleagues published their findings in JAMA Network Open.
Building on earlier findings
The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.
“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.
The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.
Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.
Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.
The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.
Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.
Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.
Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.
Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
‘An important risk factor’
Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.
The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.
Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.
However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.
The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.
“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.
The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Novel drug eases Parkinson’s-related constipation in early trial
The findings are based on 135 patients who completed 7-25 days of treatment with a daily oral dose of the drug, ENT-01, or a placebo. Complete spontaneous bowel movements (CSBMs), the primary efficacy endpoint, increased from a mean of 0.7 per week to 3.2 in individuals who took ENT-01 versus 1.2 in the placebo group.
The phase 2, multicenter, randomized trial showed that the drug “is safe and that it rapidly normalized bowel function in a dose-dependent fashion, with an effect that seems to persist for several weeks beyond the treatment period,” the researchers wrote in their paper on the research, which was published in Annals of Internal Medicine.
The researchers hypothesized that displacing aggregated alpha-synuclein from nerve cells in the gastrointestinal tract may also “slow progression of neurologic symptoms” in patients with PD by arresting the abnormal development of alpha-nucleic aggregates in the brain.
Denise Barbut, MD, cofounder, president and chief medical officer of Enterin, the company developing ENT-01, said the next step is another phase 2 trial to determine whether the drug reverses dementia or psychosis in patients with PD, before conducting a phase 3 study.
“We want to treat all nonmotor symptoms of Parkinson’s disease, not just constipation,” she said.
Constipation is an early PD symptom
Constipation is a common and persistent symptom of PD that often emerges years earlier than other symptoms such as motor deficits. Recent research has linked it to aggregates of alpha-synuclein that bind to cells in the enteric nervous system and may spread to the brain via the vagus nerve.
According to the researchers, ENT-01, a synthetic derivative of the antimicrobial compound squalamine, improves neural signaling in the gut by displacing alpha-synuclein aggregates.
In their double-blinded study, patients were randomized 3:1 to receive ENT-01 or a placebo and stratified by constipation severity to one of two starting doses: 75 mg or three placebo pills or 150 mg or six placebo pills. Doses increased until a patient reached a “prokinetic” dose, a maximum of 250 mg or 10 placebo pills, or the individual’s tolerability limit.
Dosing was fixed for the remainder of the 25 days, after which all patients took a placebo for 2 weeks followed by a 4-week washout.
In addition to more CSBMs, the treatment group had greater improvements in secondary endpoints of weekly spontaneous bowel movements (P = .002), better stool consistency (P < .001), improved ease of passage (P = .006), and less laxative use (P = .041).
There were no significant differences between the groups in scores on the Patient Assessment of Constipation Symptoms or the Patient Assessment of Constipation Quality of Life.
No deaths occurred, and there were no serious adverse events attributed to ENT-01. However, adverse events occurred in 61 (65.6%) of patients who took the drug versus 27 (47.4%) of those who took a placebo.
The most common problems were nausea, experienced by 32 (34%) in the ENT-01 group and 3 (5.3%) in the placebo group, and diarrhea, which occurred in 18 (9.4%) of those in the ENT-01 group and three (5.3%) who took the placebo.
Of 93 patients randomized to the drug (25.8%), 24 discontinued treatment before therapy ended, mostly because of nausea or diarrhea. That compared with 8 of 57 (14.1%) patients in the placebo group who stopped taking their pills before the end of the therapy period.
The researchers suggested that nausea and diarrhea might be alleviated by more gradual dosing escalation and the use of antinausea medication.
Dr. Barbut noted that a previous open-label trial of 50 patients with PD showed that ENT-01 acts locally in the gastrointestinal tract, which means it would not be absorbed into the bloodstream or interfere with other medications.
Targeting the underlying disease
Researchers noted that, in small subsets of patients with dementia or psychosis, greater improvements in those symptoms occurred among those who took ENT-01 versus those who took a placebo.
According to the study, among 11 patients with psychosis, average scores on the Scale for the Assessment of Positive Symptoms adapted for PD dropped from 6.5 to 1.8 on a 45-point scale at the end of treatment in the ENT-01 group (n = 5) and from 6.3 to 3.4 in the placebo group (n = 6).
In 28 patients with dementia, scores on the Mini-Mental State Examination improved by 2.4 points on a 30-point scale, from 24.1 to 26.5, during the treatment period for the ENT-01 group (n = 14) versus an improvement of 0.9 points, from 24.8 to 25.7, in the placebo group (n = 14).
The researchers said the findings must be evaluated in future trials dedicated to studying ENT-01’s effects on PD-related psychosis and dementia.
He added that, if findings are reproduced in a large study, the drug could have “a major impact” not just in treating constipation, for which there are no PD-specific drugs, but also in addressing neurological dysfunctions that are cardinal features of PD. “That is what is exciting to me, because we’re now talking about reversing the disease itself,” he said.
However, Dr. Barbut said it’s been difficult to get across to the medical community and to investors that a drug that acts on nerve cells in the gut might reverse neurologic symptoms by improving direct gut-brain communication. “That’s a concept that is alien to most people’s thinking,” she said.
Enterin funded the study and was responsible for the design, data collection and analysis. Its employees also participated in the interpretation of data, writing of the report, and the decision to submit the manuscript for publication. Dr. Barbut reported stock options in Enterin and patent interests in ENT-01. Fifteen other study investigators reported financial ties to Enterin and/or ENT-01 including employment, stock options, research funding, consulting fees and patent application ownership. Dr. Rao reported receiving honoraria from multiple companies that market drugs for general constipation.
The findings are based on 135 patients who completed 7-25 days of treatment with a daily oral dose of the drug, ENT-01, or a placebo. Complete spontaneous bowel movements (CSBMs), the primary efficacy endpoint, increased from a mean of 0.7 per week to 3.2 in individuals who took ENT-01 versus 1.2 in the placebo group.
The phase 2, multicenter, randomized trial showed that the drug “is safe and that it rapidly normalized bowel function in a dose-dependent fashion, with an effect that seems to persist for several weeks beyond the treatment period,” the researchers wrote in their paper on the research, which was published in Annals of Internal Medicine.
The researchers hypothesized that displacing aggregated alpha-synuclein from nerve cells in the gastrointestinal tract may also “slow progression of neurologic symptoms” in patients with PD by arresting the abnormal development of alpha-nucleic aggregates in the brain.
Denise Barbut, MD, cofounder, president and chief medical officer of Enterin, the company developing ENT-01, said the next step is another phase 2 trial to determine whether the drug reverses dementia or psychosis in patients with PD, before conducting a phase 3 study.
“We want to treat all nonmotor symptoms of Parkinson’s disease, not just constipation,” she said.
Constipation is an early PD symptom
Constipation is a common and persistent symptom of PD that often emerges years earlier than other symptoms such as motor deficits. Recent research has linked it to aggregates of alpha-synuclein that bind to cells in the enteric nervous system and may spread to the brain via the vagus nerve.
According to the researchers, ENT-01, a synthetic derivative of the antimicrobial compound squalamine, improves neural signaling in the gut by displacing alpha-synuclein aggregates.
In their double-blinded study, patients were randomized 3:1 to receive ENT-01 or a placebo and stratified by constipation severity to one of two starting doses: 75 mg or three placebo pills or 150 mg or six placebo pills. Doses increased until a patient reached a “prokinetic” dose, a maximum of 250 mg or 10 placebo pills, or the individual’s tolerability limit.
Dosing was fixed for the remainder of the 25 days, after which all patients took a placebo for 2 weeks followed by a 4-week washout.
In addition to more CSBMs, the treatment group had greater improvements in secondary endpoints of weekly spontaneous bowel movements (P = .002), better stool consistency (P < .001), improved ease of passage (P = .006), and less laxative use (P = .041).
There were no significant differences between the groups in scores on the Patient Assessment of Constipation Symptoms or the Patient Assessment of Constipation Quality of Life.
No deaths occurred, and there were no serious adverse events attributed to ENT-01. However, adverse events occurred in 61 (65.6%) of patients who took the drug versus 27 (47.4%) of those who took a placebo.
The most common problems were nausea, experienced by 32 (34%) in the ENT-01 group and 3 (5.3%) in the placebo group, and diarrhea, which occurred in 18 (9.4%) of those in the ENT-01 group and three (5.3%) who took the placebo.
Of 93 patients randomized to the drug (25.8%), 24 discontinued treatment before therapy ended, mostly because of nausea or diarrhea. That compared with 8 of 57 (14.1%) patients in the placebo group who stopped taking their pills before the end of the therapy period.
The researchers suggested that nausea and diarrhea might be alleviated by more gradual dosing escalation and the use of antinausea medication.
Dr. Barbut noted that a previous open-label trial of 50 patients with PD showed that ENT-01 acts locally in the gastrointestinal tract, which means it would not be absorbed into the bloodstream or interfere with other medications.
Targeting the underlying disease
Researchers noted that, in small subsets of patients with dementia or psychosis, greater improvements in those symptoms occurred among those who took ENT-01 versus those who took a placebo.
According to the study, among 11 patients with psychosis, average scores on the Scale for the Assessment of Positive Symptoms adapted for PD dropped from 6.5 to 1.8 on a 45-point scale at the end of treatment in the ENT-01 group (n = 5) and from 6.3 to 3.4 in the placebo group (n = 6).
In 28 patients with dementia, scores on the Mini-Mental State Examination improved by 2.4 points on a 30-point scale, from 24.1 to 26.5, during the treatment period for the ENT-01 group (n = 14) versus an improvement of 0.9 points, from 24.8 to 25.7, in the placebo group (n = 14).
The researchers said the findings must be evaluated in future trials dedicated to studying ENT-01’s effects on PD-related psychosis and dementia.
He added that, if findings are reproduced in a large study, the drug could have “a major impact” not just in treating constipation, for which there are no PD-specific drugs, but also in addressing neurological dysfunctions that are cardinal features of PD. “That is what is exciting to me, because we’re now talking about reversing the disease itself,” he said.
However, Dr. Barbut said it’s been difficult to get across to the medical community and to investors that a drug that acts on nerve cells in the gut might reverse neurologic symptoms by improving direct gut-brain communication. “That’s a concept that is alien to most people’s thinking,” she said.
Enterin funded the study and was responsible for the design, data collection and analysis. Its employees also participated in the interpretation of data, writing of the report, and the decision to submit the manuscript for publication. Dr. Barbut reported stock options in Enterin and patent interests in ENT-01. Fifteen other study investigators reported financial ties to Enterin and/or ENT-01 including employment, stock options, research funding, consulting fees and patent application ownership. Dr. Rao reported receiving honoraria from multiple companies that market drugs for general constipation.
The findings are based on 135 patients who completed 7-25 days of treatment with a daily oral dose of the drug, ENT-01, or a placebo. Complete spontaneous bowel movements (CSBMs), the primary efficacy endpoint, increased from a mean of 0.7 per week to 3.2 in individuals who took ENT-01 versus 1.2 in the placebo group.
The phase 2, multicenter, randomized trial showed that the drug “is safe and that it rapidly normalized bowel function in a dose-dependent fashion, with an effect that seems to persist for several weeks beyond the treatment period,” the researchers wrote in their paper on the research, which was published in Annals of Internal Medicine.
The researchers hypothesized that displacing aggregated alpha-synuclein from nerve cells in the gastrointestinal tract may also “slow progression of neurologic symptoms” in patients with PD by arresting the abnormal development of alpha-nucleic aggregates in the brain.
Denise Barbut, MD, cofounder, president and chief medical officer of Enterin, the company developing ENT-01, said the next step is another phase 2 trial to determine whether the drug reverses dementia or psychosis in patients with PD, before conducting a phase 3 study.
“We want to treat all nonmotor symptoms of Parkinson’s disease, not just constipation,” she said.
Constipation is an early PD symptom
Constipation is a common and persistent symptom of PD that often emerges years earlier than other symptoms such as motor deficits. Recent research has linked it to aggregates of alpha-synuclein that bind to cells in the enteric nervous system and may spread to the brain via the vagus nerve.
According to the researchers, ENT-01, a synthetic derivative of the antimicrobial compound squalamine, improves neural signaling in the gut by displacing alpha-synuclein aggregates.
In their double-blinded study, patients were randomized 3:1 to receive ENT-01 or a placebo and stratified by constipation severity to one of two starting doses: 75 mg or three placebo pills or 150 mg or six placebo pills. Doses increased until a patient reached a “prokinetic” dose, a maximum of 250 mg or 10 placebo pills, or the individual’s tolerability limit.
Dosing was fixed for the remainder of the 25 days, after which all patients took a placebo for 2 weeks followed by a 4-week washout.
In addition to more CSBMs, the treatment group had greater improvements in secondary endpoints of weekly spontaneous bowel movements (P = .002), better stool consistency (P < .001), improved ease of passage (P = .006), and less laxative use (P = .041).
There were no significant differences between the groups in scores on the Patient Assessment of Constipation Symptoms or the Patient Assessment of Constipation Quality of Life.
No deaths occurred, and there were no serious adverse events attributed to ENT-01. However, adverse events occurred in 61 (65.6%) of patients who took the drug versus 27 (47.4%) of those who took a placebo.
The most common problems were nausea, experienced by 32 (34%) in the ENT-01 group and 3 (5.3%) in the placebo group, and diarrhea, which occurred in 18 (9.4%) of those in the ENT-01 group and three (5.3%) who took the placebo.
Of 93 patients randomized to the drug (25.8%), 24 discontinued treatment before therapy ended, mostly because of nausea or diarrhea. That compared with 8 of 57 (14.1%) patients in the placebo group who stopped taking their pills before the end of the therapy period.
The researchers suggested that nausea and diarrhea might be alleviated by more gradual dosing escalation and the use of antinausea medication.
Dr. Barbut noted that a previous open-label trial of 50 patients with PD showed that ENT-01 acts locally in the gastrointestinal tract, which means it would not be absorbed into the bloodstream or interfere with other medications.
Targeting the underlying disease
Researchers noted that, in small subsets of patients with dementia or psychosis, greater improvements in those symptoms occurred among those who took ENT-01 versus those who took a placebo.
According to the study, among 11 patients with psychosis, average scores on the Scale for the Assessment of Positive Symptoms adapted for PD dropped from 6.5 to 1.8 on a 45-point scale at the end of treatment in the ENT-01 group (n = 5) and from 6.3 to 3.4 in the placebo group (n = 6).
In 28 patients with dementia, scores on the Mini-Mental State Examination improved by 2.4 points on a 30-point scale, from 24.1 to 26.5, during the treatment period for the ENT-01 group (n = 14) versus an improvement of 0.9 points, from 24.8 to 25.7, in the placebo group (n = 14).
The researchers said the findings must be evaluated in future trials dedicated to studying ENT-01’s effects on PD-related psychosis and dementia.
He added that, if findings are reproduced in a large study, the drug could have “a major impact” not just in treating constipation, for which there are no PD-specific drugs, but also in addressing neurological dysfunctions that are cardinal features of PD. “That is what is exciting to me, because we’re now talking about reversing the disease itself,” he said.
However, Dr. Barbut said it’s been difficult to get across to the medical community and to investors that a drug that acts on nerve cells in the gut might reverse neurologic symptoms by improving direct gut-brain communication. “That’s a concept that is alien to most people’s thinking,” she said.
Enterin funded the study and was responsible for the design, data collection and analysis. Its employees also participated in the interpretation of data, writing of the report, and the decision to submit the manuscript for publication. Dr. Barbut reported stock options in Enterin and patent interests in ENT-01. Fifteen other study investigators reported financial ties to Enterin and/or ENT-01 including employment, stock options, research funding, consulting fees and patent application ownership. Dr. Rao reported receiving honoraria from multiple companies that market drugs for general constipation.
FROM ANNALS OF INTERNAL MEDICINE
DTC telemedicine expands access to gender-affirming therapy
Direct-to-consumer telemedicine services that provide gender-affirming hormone therapy appear to follow evidence-based guidelines and charge about the same as brick-and-mortar medical centers, according to researchers who reviewed the platforms’ websites.
The findings suggest that virtual care “may be a good option” for transgender, nonbinary, and intersex people, who often report difficulty finding physicians they trust, Erin Jesse, MD, a fifth-year urology resident at University Hospitals Cleveland Medical Center, who is the first author of the study, told this news organization.
Dr. Jesse’s group presented their findings at a joint scientific meeting of the Sexual Medicine Society of North America and the International Society for Sexual Medicine in Miami. The results have not been published in a peer-reviewed journal.
New direct-to-consumer telemedicine companies have emerged with gender-diverse staff and services tailored to the needs of these individuals. They offer “a more inclusive feel” than might be encountered at a physician’s office, Dr. Jesse said.
Confirming that these companies adhere to standards of care and cost-effectiveness “is especially important considering the reduced access to care and potentially increased vulnerability of the gender-diverse population,” she and her colleagues wrote.
From a Google search in March, the team identified six U.S.-based platforms that offer gender-affirming medical therapy: FOLX, True U Clinic, QueerDoc, Queer Med, TransClinique, and Plume.
From information posted on the companies’ websites, the researchers determined that all aligned with the World Professional Association for Transgender Health’s Standards of Care in two areas: use of an informed consent model to ensure that patients have sufficient information and understanding to decide on their own treatment and endorsement of frequent laboratory monitoring of hormone levels in early stages of treatment.
The team also compared the costs listed on the websites for the first year of therapy to the costs of similar care at a tertiary center, as determined using University Hospitals Cleveland Medical Center’s online estimator.
The platforms offered various pricing models, including fee-for-service and monthly membership plans ranging from $59 to $139. For individuals without insurance, estimates ranged from $1,022 to $1,428 for oral estradiol and from $1,184 to $1,668 for intramuscular testosterone from the online companies, compared with $1,184 and $1,216, respectively, at the tertiary center.
Although some platforms accept insurance, the researchers were not able to evaluate the cost of using private insurance or Medicaid, Dr. Jesse said. She noted that transgender individuals are more likely to lack insurance than are cisgender patients.
The team also assessed the scope of services. All companies offered legal help with changes to names and gender markers, such as “M” and “F.” Three or more companies offered preexposure prophylaxis to prevent HIV infection, treatment for erectile dysfunction, referrals for surgery, and medical letters of support for surgery.
Two offered puberty blockers, although the researchers were unable to determine the risk of adolescents obtaining treatment without proper assessments, because details of those services are not disclosed on websites, Dr. Jesse said.
An avenue of further research would be to interview patients to learn how platforms operate in practice and whether patients are properly assessed before treatment. “Those sorts of questions we can’t answer just by looking at the websites,” she said.
However, Charlotte Hoffman, JD, senior policy counsel for the National Center for Transgender Equality, an advocacy group, said she does not harbor concerns about patients being treated inappropriately simply because care is virtual. All clinicians who provide gender-affirming care face potential repercussions, such as malpractice lawsuits or state disciplinary action, if they veer from treatment guidelines, she said.
“I don’t necessarily take the premise that telehealth is inherently worse than in-person care as a given,” Ms. Hoffman said.
During the COVID-19 pandemic, Ms. Hoffman added, direct-to-consumer telemedicine has expanded access for individuals in rural areas, people with disabilities, and those who live in places where in-person providers of transgender care face public hostility, although individuals without the resources to pay may still be left out.
What might happen to that access if telemedicine restrictions that were loosened during the pandemic are reinstated is unclear, she said.
The researchers and Ms. Hoffman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Direct-to-consumer telemedicine services that provide gender-affirming hormone therapy appear to follow evidence-based guidelines and charge about the same as brick-and-mortar medical centers, according to researchers who reviewed the platforms’ websites.
The findings suggest that virtual care “may be a good option” for transgender, nonbinary, and intersex people, who often report difficulty finding physicians they trust, Erin Jesse, MD, a fifth-year urology resident at University Hospitals Cleveland Medical Center, who is the first author of the study, told this news organization.
Dr. Jesse’s group presented their findings at a joint scientific meeting of the Sexual Medicine Society of North America and the International Society for Sexual Medicine in Miami. The results have not been published in a peer-reviewed journal.
New direct-to-consumer telemedicine companies have emerged with gender-diverse staff and services tailored to the needs of these individuals. They offer “a more inclusive feel” than might be encountered at a physician’s office, Dr. Jesse said.
Confirming that these companies adhere to standards of care and cost-effectiveness “is especially important considering the reduced access to care and potentially increased vulnerability of the gender-diverse population,” she and her colleagues wrote.
From a Google search in March, the team identified six U.S.-based platforms that offer gender-affirming medical therapy: FOLX, True U Clinic, QueerDoc, Queer Med, TransClinique, and Plume.
From information posted on the companies’ websites, the researchers determined that all aligned with the World Professional Association for Transgender Health’s Standards of Care in two areas: use of an informed consent model to ensure that patients have sufficient information and understanding to decide on their own treatment and endorsement of frequent laboratory monitoring of hormone levels in early stages of treatment.
The team also compared the costs listed on the websites for the first year of therapy to the costs of similar care at a tertiary center, as determined using University Hospitals Cleveland Medical Center’s online estimator.
The platforms offered various pricing models, including fee-for-service and monthly membership plans ranging from $59 to $139. For individuals without insurance, estimates ranged from $1,022 to $1,428 for oral estradiol and from $1,184 to $1,668 for intramuscular testosterone from the online companies, compared with $1,184 and $1,216, respectively, at the tertiary center.
Although some platforms accept insurance, the researchers were not able to evaluate the cost of using private insurance or Medicaid, Dr. Jesse said. She noted that transgender individuals are more likely to lack insurance than are cisgender patients.
The team also assessed the scope of services. All companies offered legal help with changes to names and gender markers, such as “M” and “F.” Three or more companies offered preexposure prophylaxis to prevent HIV infection, treatment for erectile dysfunction, referrals for surgery, and medical letters of support for surgery.
Two offered puberty blockers, although the researchers were unable to determine the risk of adolescents obtaining treatment without proper assessments, because details of those services are not disclosed on websites, Dr. Jesse said.
An avenue of further research would be to interview patients to learn how platforms operate in practice and whether patients are properly assessed before treatment. “Those sorts of questions we can’t answer just by looking at the websites,” she said.
However, Charlotte Hoffman, JD, senior policy counsel for the National Center for Transgender Equality, an advocacy group, said she does not harbor concerns about patients being treated inappropriately simply because care is virtual. All clinicians who provide gender-affirming care face potential repercussions, such as malpractice lawsuits or state disciplinary action, if they veer from treatment guidelines, she said.
“I don’t necessarily take the premise that telehealth is inherently worse than in-person care as a given,” Ms. Hoffman said.
During the COVID-19 pandemic, Ms. Hoffman added, direct-to-consumer telemedicine has expanded access for individuals in rural areas, people with disabilities, and those who live in places where in-person providers of transgender care face public hostility, although individuals without the resources to pay may still be left out.
What might happen to that access if telemedicine restrictions that were loosened during the pandemic are reinstated is unclear, she said.
The researchers and Ms. Hoffman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Direct-to-consumer telemedicine services that provide gender-affirming hormone therapy appear to follow evidence-based guidelines and charge about the same as brick-and-mortar medical centers, according to researchers who reviewed the platforms’ websites.
The findings suggest that virtual care “may be a good option” for transgender, nonbinary, and intersex people, who often report difficulty finding physicians they trust, Erin Jesse, MD, a fifth-year urology resident at University Hospitals Cleveland Medical Center, who is the first author of the study, told this news organization.
Dr. Jesse’s group presented their findings at a joint scientific meeting of the Sexual Medicine Society of North America and the International Society for Sexual Medicine in Miami. The results have not been published in a peer-reviewed journal.
New direct-to-consumer telemedicine companies have emerged with gender-diverse staff and services tailored to the needs of these individuals. They offer “a more inclusive feel” than might be encountered at a physician’s office, Dr. Jesse said.
Confirming that these companies adhere to standards of care and cost-effectiveness “is especially important considering the reduced access to care and potentially increased vulnerability of the gender-diverse population,” she and her colleagues wrote.
From a Google search in March, the team identified six U.S.-based platforms that offer gender-affirming medical therapy: FOLX, True U Clinic, QueerDoc, Queer Med, TransClinique, and Plume.
From information posted on the companies’ websites, the researchers determined that all aligned with the World Professional Association for Transgender Health’s Standards of Care in two areas: use of an informed consent model to ensure that patients have sufficient information and understanding to decide on their own treatment and endorsement of frequent laboratory monitoring of hormone levels in early stages of treatment.
The team also compared the costs listed on the websites for the first year of therapy to the costs of similar care at a tertiary center, as determined using University Hospitals Cleveland Medical Center’s online estimator.
The platforms offered various pricing models, including fee-for-service and monthly membership plans ranging from $59 to $139. For individuals without insurance, estimates ranged from $1,022 to $1,428 for oral estradiol and from $1,184 to $1,668 for intramuscular testosterone from the online companies, compared with $1,184 and $1,216, respectively, at the tertiary center.
Although some platforms accept insurance, the researchers were not able to evaluate the cost of using private insurance or Medicaid, Dr. Jesse said. She noted that transgender individuals are more likely to lack insurance than are cisgender patients.
The team also assessed the scope of services. All companies offered legal help with changes to names and gender markers, such as “M” and “F.” Three or more companies offered preexposure prophylaxis to prevent HIV infection, treatment for erectile dysfunction, referrals for surgery, and medical letters of support for surgery.
Two offered puberty blockers, although the researchers were unable to determine the risk of adolescents obtaining treatment without proper assessments, because details of those services are not disclosed on websites, Dr. Jesse said.
An avenue of further research would be to interview patients to learn how platforms operate in practice and whether patients are properly assessed before treatment. “Those sorts of questions we can’t answer just by looking at the websites,” she said.
However, Charlotte Hoffman, JD, senior policy counsel for the National Center for Transgender Equality, an advocacy group, said she does not harbor concerns about patients being treated inappropriately simply because care is virtual. All clinicians who provide gender-affirming care face potential repercussions, such as malpractice lawsuits or state disciplinary action, if they veer from treatment guidelines, she said.
“I don’t necessarily take the premise that telehealth is inherently worse than in-person care as a given,” Ms. Hoffman said.
During the COVID-19 pandemic, Ms. Hoffman added, direct-to-consumer telemedicine has expanded access for individuals in rural areas, people with disabilities, and those who live in places where in-person providers of transgender care face public hostility, although individuals without the resources to pay may still be left out.
What might happen to that access if telemedicine restrictions that were loosened during the pandemic are reinstated is unclear, she said.
The researchers and Ms. Hoffman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rapid point-of-care test could help avoid inappropriate antibiotic prescribing
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
FROM JAMA NETWORK OPEN
Pediatricians urged to check for vision problems after concussion
Pediatricians should consider screening children suspected of having a concussion for resulting vision problems that are often overlooked, according to the American Academy of Pediatrics.
Christina Master, MD, a pediatrician and sports medicine specialist at the Children’s Hospital of Philadelphia, said many doctors don’t think of vision problems when examining children who’ve experienced a head injury. But the issues are common and can significantly affect a child’s performance in school and sports, and disrupt daily life.
Dr. Master led a team of sports medicine and vision specialists who wrote an AAP policy statement on vision and concussion. She summarized the new recommendations during a plenary session Oct. 9 at the American Academy of Pediatrics National Conference.
Dr. Master told this news organization that the vast majority of the estimated 1.4 million U.S. children and adolescents who have concussions annually are treated in pediatricians’ offices.
Up to 40% of young patients experience symptoms such as blurred vision, light sensitivity, and double vision following a concussion, the panel said. In addition, children with vision problems are more likely to have prolonged recoveries and delays in returning to school than children who have concussions but don’t have similar eyesight issues.
Concussions affect neurologic pathways of the visual system and disturb basic functions such as the ability of the eyes to change focus from a distant object to a near one.
Dr. Master said most pediatricians do not routinely check for vision problems following a concussion, and children themselves may not recognize that they have vision deficits “unless you ask them very specifically.”
In addition to asking children about their vision, the policy statement recommends pediatricians conduct a thorough exam to assess ocular alignment, the ability to track a moving object, and the ability to maintain focus on an image while moving.
Dr. Master said that an assessment of vision and balance, which is described in an accompanying clinical report, lasts about 5 minutes and is easy for pediatricians to learn.
Managing vision problems
Pediatricians can guide parents in talking to their child’s school about accommodations such as extra time on classroom tasks, creating materials with enlarged fonts, and using preprinted or audio notes, the statement said.
At school, vision deficits can interfere with reading by causing children to skip words, lose their place, become fatigued, or lose interest, according to the statement.
Children can also take breaks from visual stressors such as bright lights and screens, and use prescription glasses temporarily to correct blurred vision, the panel noted.
Although most children will recover from a concussion on their own within 4 weeks, up to one-third will have persistent symptoms and may benefit from seeing a specialist who can provide treatment such as rehabilitative exercises. While evidence suggests that referring some children to specialty care within a week of a concussion improves outcomes, the signs of who would benefit are not always clear, according to the panel.
Specialties such as sports medicine, neurology, physiatry, otorhinolaryngology, and occupational therapy may provide care for prolonged symptoms, Dr. Master said.
The panel noted that more study is needed on treatment options such as rehabilitation exercises, which have been shown to help with balance and dizziness.
Dr. Master said the panel did not recommend that pediatricians provide a home exercise program to treat concussion, as she does in her practice, explaining that “it’s not clear that it’s necessary for all kids.”
One author of the policy statement, Ankoor Shah, MD, PhD, reported an intellectual property relationship with Rebion involving a patent application for a pediatric vision screener. Others, including Dr. Master, reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pediatricians should consider screening children suspected of having a concussion for resulting vision problems that are often overlooked, according to the American Academy of Pediatrics.
Christina Master, MD, a pediatrician and sports medicine specialist at the Children’s Hospital of Philadelphia, said many doctors don’t think of vision problems when examining children who’ve experienced a head injury. But the issues are common and can significantly affect a child’s performance in school and sports, and disrupt daily life.
Dr. Master led a team of sports medicine and vision specialists who wrote an AAP policy statement on vision and concussion. She summarized the new recommendations during a plenary session Oct. 9 at the American Academy of Pediatrics National Conference.
Dr. Master told this news organization that the vast majority of the estimated 1.4 million U.S. children and adolescents who have concussions annually are treated in pediatricians’ offices.
Up to 40% of young patients experience symptoms such as blurred vision, light sensitivity, and double vision following a concussion, the panel said. In addition, children with vision problems are more likely to have prolonged recoveries and delays in returning to school than children who have concussions but don’t have similar eyesight issues.
Concussions affect neurologic pathways of the visual system and disturb basic functions such as the ability of the eyes to change focus from a distant object to a near one.
Dr. Master said most pediatricians do not routinely check for vision problems following a concussion, and children themselves may not recognize that they have vision deficits “unless you ask them very specifically.”
In addition to asking children about their vision, the policy statement recommends pediatricians conduct a thorough exam to assess ocular alignment, the ability to track a moving object, and the ability to maintain focus on an image while moving.
Dr. Master said that an assessment of vision and balance, which is described in an accompanying clinical report, lasts about 5 minutes and is easy for pediatricians to learn.
Managing vision problems
Pediatricians can guide parents in talking to their child’s school about accommodations such as extra time on classroom tasks, creating materials with enlarged fonts, and using preprinted or audio notes, the statement said.
At school, vision deficits can interfere with reading by causing children to skip words, lose their place, become fatigued, or lose interest, according to the statement.
Children can also take breaks from visual stressors such as bright lights and screens, and use prescription glasses temporarily to correct blurred vision, the panel noted.
Although most children will recover from a concussion on their own within 4 weeks, up to one-third will have persistent symptoms and may benefit from seeing a specialist who can provide treatment such as rehabilitative exercises. While evidence suggests that referring some children to specialty care within a week of a concussion improves outcomes, the signs of who would benefit are not always clear, according to the panel.
Specialties such as sports medicine, neurology, physiatry, otorhinolaryngology, and occupational therapy may provide care for prolonged symptoms, Dr. Master said.
The panel noted that more study is needed on treatment options such as rehabilitation exercises, which have been shown to help with balance and dizziness.
Dr. Master said the panel did not recommend that pediatricians provide a home exercise program to treat concussion, as she does in her practice, explaining that “it’s not clear that it’s necessary for all kids.”
One author of the policy statement, Ankoor Shah, MD, PhD, reported an intellectual property relationship with Rebion involving a patent application for a pediatric vision screener. Others, including Dr. Master, reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pediatricians should consider screening children suspected of having a concussion for resulting vision problems that are often overlooked, according to the American Academy of Pediatrics.
Christina Master, MD, a pediatrician and sports medicine specialist at the Children’s Hospital of Philadelphia, said many doctors don’t think of vision problems when examining children who’ve experienced a head injury. But the issues are common and can significantly affect a child’s performance in school and sports, and disrupt daily life.
Dr. Master led a team of sports medicine and vision specialists who wrote an AAP policy statement on vision and concussion. She summarized the new recommendations during a plenary session Oct. 9 at the American Academy of Pediatrics National Conference.
Dr. Master told this news organization that the vast majority of the estimated 1.4 million U.S. children and adolescents who have concussions annually are treated in pediatricians’ offices.
Up to 40% of young patients experience symptoms such as blurred vision, light sensitivity, and double vision following a concussion, the panel said. In addition, children with vision problems are more likely to have prolonged recoveries and delays in returning to school than children who have concussions but don’t have similar eyesight issues.
Concussions affect neurologic pathways of the visual system and disturb basic functions such as the ability of the eyes to change focus from a distant object to a near one.
Dr. Master said most pediatricians do not routinely check for vision problems following a concussion, and children themselves may not recognize that they have vision deficits “unless you ask them very specifically.”
In addition to asking children about their vision, the policy statement recommends pediatricians conduct a thorough exam to assess ocular alignment, the ability to track a moving object, and the ability to maintain focus on an image while moving.
Dr. Master said that an assessment of vision and balance, which is described in an accompanying clinical report, lasts about 5 minutes and is easy for pediatricians to learn.
Managing vision problems
Pediatricians can guide parents in talking to their child’s school about accommodations such as extra time on classroom tasks, creating materials with enlarged fonts, and using preprinted or audio notes, the statement said.
At school, vision deficits can interfere with reading by causing children to skip words, lose their place, become fatigued, or lose interest, according to the statement.
Children can also take breaks from visual stressors such as bright lights and screens, and use prescription glasses temporarily to correct blurred vision, the panel noted.
Although most children will recover from a concussion on their own within 4 weeks, up to one-third will have persistent symptoms and may benefit from seeing a specialist who can provide treatment such as rehabilitative exercises. While evidence suggests that referring some children to specialty care within a week of a concussion improves outcomes, the signs of who would benefit are not always clear, according to the panel.
Specialties such as sports medicine, neurology, physiatry, otorhinolaryngology, and occupational therapy may provide care for prolonged symptoms, Dr. Master said.
The panel noted that more study is needed on treatment options such as rehabilitation exercises, which have been shown to help with balance and dizziness.
Dr. Master said the panel did not recommend that pediatricians provide a home exercise program to treat concussion, as she does in her practice, explaining that “it’s not clear that it’s necessary for all kids.”
One author of the policy statement, Ankoor Shah, MD, PhD, reported an intellectual property relationship with Rebion involving a patent application for a pediatric vision screener. Others, including Dr. Master, reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAP 2022
With sleuth work, pediatricians can identify genetic disorders
Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist.
“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”
Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
Spectrums of disease
Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.
With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.
Beckwith-Wiedemann syndrome is a prime example. The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.
Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.
To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.
Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.
Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
Spotting a “compilation of features”
Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.
For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”
Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.
One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.
The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.
In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.
She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.
Dr. Kalish reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist.
“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”
Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
Spectrums of disease
Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.
With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.
Beckwith-Wiedemann syndrome is a prime example. The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.
Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.
To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.
Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.
Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
Spotting a “compilation of features”
Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.
For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”
Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.
One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.
The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.
In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.
She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.
Dr. Kalish reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist.
“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”
Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
Spectrums of disease
Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.
With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.
Beckwith-Wiedemann syndrome is a prime example. The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.
Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.
To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.
Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.
Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
Spotting a “compilation of features”
Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.
For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”
Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.
One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.
The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.
In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.
She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.
Dr. Kalish reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAP 2022
Walking intensity and step count are linked to health benefits
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
FROM JAMA INTERNAL MEDICINE