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Number of FPs, Procedures They Perform Dropping
At the same time the Medicare population is growing, the number of family practice (FP) physicians and the number of procedures they perform are decreasing, according to a new analysis in Annals of Family Medicine.
“The reasons might represent a changing scope of family practice, increasing referrals, shifting tasks to [physician assistants] and [nurse practitioners], or some combination,” wrote the authors, led by Robert McKenna, DMSc, MPH, PA-C, with Marshall B. Ketchum University, Fullerton, California. But understanding the reasons may be important to improve training programs.
The Council of Academic Family Medicine (CAFM) in 2014 addressed variability in how FPs perform procedures with a consensus statement on 44 procedures FPs should be competent to perform after a family medicine residency and 24 more for which residency programs should offer training.
Researchers wanted to see how often the procedures were being done so they performed a retrospective, observational study of the Medicare Part B cohort to understand how often FPs report CAFM-recommended procedures in an outpatient setting. They used data from 2014 to 2021, the most recent years for which data were available, and modified the list of procedures for Medicare beneficiaries to match with Current Procedural Terminology codes.
Procedures Dropped by a Third in 8 Years
For the 8 years ending in 2021, there was a 33% decrease in outpatient procedures filed and a 36% decrease in the number of FPs who filed them, according to the paper. However, the number of FPs who treat Medicare beneficiaries has remained relatively stable. Almost all procedures performed were for the skin; musculoskeletal; eyes, ears, nose, and throat; and pulmonary categories.
There was a 17% decrease in every category of modified CAFM procedures between 2014 and 2019 before the pandemic.
Concurrently, the U.S. Bureau of Labor Statistics reported a 7% decrease in clinically active FPs from 2013 to 2022; 100,940 FPs were employed clinically in 2022. The Association of American Medical Colleges estimates a shortage of 17,800-48,000 primary care physicians by 2034.
“In 2021, the number of Medicare Part B claims by FPs for all [modified] CAFM outpatient procedures was reported by 12% of these clinicians and represented less than 1% of all CPT claims submitted,” the researchers wrote.
“Meanwhile, the 17% of Americans aged [at least] 65 years is projected to represent 20% of the U.S. population by 2030,” the authors pointed out.
The reasons for the decrease in procedures need further study, the authors said. From 2010 to 2020, there was a 30% and 47% increase in the employment of PAs and NPs, respectively, across all specialties, many employed in primary care. And 42% and 56% of family physicians reported working with PAs and NPs, respectively, from 2014 to 2018, according to the paper.
One explanation is a shifting of roles. “NPs and PAs might increasingly serve as proceduralists, freeing FPs to focus on other aspects of their practice such as complex chronic disease management or annual wellness visits,” the authors wrote.
It’s also possible that more Medicare-eligible Americans are being referred to various specialists such as urologists, gynecologists, and cardiologists, they speculated, adding that, “because demographic trends show an increasingly older population, family medicine training programs might need to adjust to meet this change.”
Among the limitations of the data are that publicly available Medicare data are limited to the approximately 60% of beneficiaries who are traditional Part B enrollees. Those enrolled in Medicare Advantage plans were excluded.
The work was supported in part by a Small Research Grant from the American Academy of Physician Associates in 2022. The authors reported no relevant financial relationships.
At the same time the Medicare population is growing, the number of family practice (FP) physicians and the number of procedures they perform are decreasing, according to a new analysis in Annals of Family Medicine.
“The reasons might represent a changing scope of family practice, increasing referrals, shifting tasks to [physician assistants] and [nurse practitioners], or some combination,” wrote the authors, led by Robert McKenna, DMSc, MPH, PA-C, with Marshall B. Ketchum University, Fullerton, California. But understanding the reasons may be important to improve training programs.
The Council of Academic Family Medicine (CAFM) in 2014 addressed variability in how FPs perform procedures with a consensus statement on 44 procedures FPs should be competent to perform after a family medicine residency and 24 more for which residency programs should offer training.
Researchers wanted to see how often the procedures were being done so they performed a retrospective, observational study of the Medicare Part B cohort to understand how often FPs report CAFM-recommended procedures in an outpatient setting. They used data from 2014 to 2021, the most recent years for which data were available, and modified the list of procedures for Medicare beneficiaries to match with Current Procedural Terminology codes.
Procedures Dropped by a Third in 8 Years
For the 8 years ending in 2021, there was a 33% decrease in outpatient procedures filed and a 36% decrease in the number of FPs who filed them, according to the paper. However, the number of FPs who treat Medicare beneficiaries has remained relatively stable. Almost all procedures performed were for the skin; musculoskeletal; eyes, ears, nose, and throat; and pulmonary categories.
There was a 17% decrease in every category of modified CAFM procedures between 2014 and 2019 before the pandemic.
Concurrently, the U.S. Bureau of Labor Statistics reported a 7% decrease in clinically active FPs from 2013 to 2022; 100,940 FPs were employed clinically in 2022. The Association of American Medical Colleges estimates a shortage of 17,800-48,000 primary care physicians by 2034.
“In 2021, the number of Medicare Part B claims by FPs for all [modified] CAFM outpatient procedures was reported by 12% of these clinicians and represented less than 1% of all CPT claims submitted,” the researchers wrote.
“Meanwhile, the 17% of Americans aged [at least] 65 years is projected to represent 20% of the U.S. population by 2030,” the authors pointed out.
The reasons for the decrease in procedures need further study, the authors said. From 2010 to 2020, there was a 30% and 47% increase in the employment of PAs and NPs, respectively, across all specialties, many employed in primary care. And 42% and 56% of family physicians reported working with PAs and NPs, respectively, from 2014 to 2018, according to the paper.
One explanation is a shifting of roles. “NPs and PAs might increasingly serve as proceduralists, freeing FPs to focus on other aspects of their practice such as complex chronic disease management or annual wellness visits,” the authors wrote.
It’s also possible that more Medicare-eligible Americans are being referred to various specialists such as urologists, gynecologists, and cardiologists, they speculated, adding that, “because demographic trends show an increasingly older population, family medicine training programs might need to adjust to meet this change.”
Among the limitations of the data are that publicly available Medicare data are limited to the approximately 60% of beneficiaries who are traditional Part B enrollees. Those enrolled in Medicare Advantage plans were excluded.
The work was supported in part by a Small Research Grant from the American Academy of Physician Associates in 2022. The authors reported no relevant financial relationships.
At the same time the Medicare population is growing, the number of family practice (FP) physicians and the number of procedures they perform are decreasing, according to a new analysis in Annals of Family Medicine.
“The reasons might represent a changing scope of family practice, increasing referrals, shifting tasks to [physician assistants] and [nurse practitioners], or some combination,” wrote the authors, led by Robert McKenna, DMSc, MPH, PA-C, with Marshall B. Ketchum University, Fullerton, California. But understanding the reasons may be important to improve training programs.
The Council of Academic Family Medicine (CAFM) in 2014 addressed variability in how FPs perform procedures with a consensus statement on 44 procedures FPs should be competent to perform after a family medicine residency and 24 more for which residency programs should offer training.
Researchers wanted to see how often the procedures were being done so they performed a retrospective, observational study of the Medicare Part B cohort to understand how often FPs report CAFM-recommended procedures in an outpatient setting. They used data from 2014 to 2021, the most recent years for which data were available, and modified the list of procedures for Medicare beneficiaries to match with Current Procedural Terminology codes.
Procedures Dropped by a Third in 8 Years
For the 8 years ending in 2021, there was a 33% decrease in outpatient procedures filed and a 36% decrease in the number of FPs who filed them, according to the paper. However, the number of FPs who treat Medicare beneficiaries has remained relatively stable. Almost all procedures performed were for the skin; musculoskeletal; eyes, ears, nose, and throat; and pulmonary categories.
There was a 17% decrease in every category of modified CAFM procedures between 2014 and 2019 before the pandemic.
Concurrently, the U.S. Bureau of Labor Statistics reported a 7% decrease in clinically active FPs from 2013 to 2022; 100,940 FPs were employed clinically in 2022. The Association of American Medical Colleges estimates a shortage of 17,800-48,000 primary care physicians by 2034.
“In 2021, the number of Medicare Part B claims by FPs for all [modified] CAFM outpatient procedures was reported by 12% of these clinicians and represented less than 1% of all CPT claims submitted,” the researchers wrote.
“Meanwhile, the 17% of Americans aged [at least] 65 years is projected to represent 20% of the U.S. population by 2030,” the authors pointed out.
The reasons for the decrease in procedures need further study, the authors said. From 2010 to 2020, there was a 30% and 47% increase in the employment of PAs and NPs, respectively, across all specialties, many employed in primary care. And 42% and 56% of family physicians reported working with PAs and NPs, respectively, from 2014 to 2018, according to the paper.
One explanation is a shifting of roles. “NPs and PAs might increasingly serve as proceduralists, freeing FPs to focus on other aspects of their practice such as complex chronic disease management or annual wellness visits,” the authors wrote.
It’s also possible that more Medicare-eligible Americans are being referred to various specialists such as urologists, gynecologists, and cardiologists, they speculated, adding that, “because demographic trends show an increasingly older population, family medicine training programs might need to adjust to meet this change.”
Among the limitations of the data are that publicly available Medicare data are limited to the approximately 60% of beneficiaries who are traditional Part B enrollees. Those enrolled in Medicare Advantage plans were excluded.
The work was supported in part by a Small Research Grant from the American Academy of Physician Associates in 2022. The authors reported no relevant financial relationships.
FROM ANNALS OF FAMILY MEDICINE
Inavolisib Added to Standard Tx Shows Sustained Benefit in Advanced BC
The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.
The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).
“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.
In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
Methods and Results
The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.
At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.
In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.
Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.
There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.
Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
Rationale for Using PFS2 as Endpoint
The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.
“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.
“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”
The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.
The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.
The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).
“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.
In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
Methods and Results
The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.
At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.
In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.
Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.
There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.
Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
Rationale for Using PFS2 as Endpoint
The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.
“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.
“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”
The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.
The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.
The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).
“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.
In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
Methods and Results
The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.
At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.
In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.
Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.
There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.
Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
Rationale for Using PFS2 as Endpoint
The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.
“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.
“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”
The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.
FROM ASCO 2024
FDA Expands Pembrolizumab Approval for Endometrial Cancer
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
Polycystic Ovarian Syndrome: New Science Offers Old Remedy
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
FROM SCIENCE
Urgent Need for Better Care, New Policies to Lower Insomnia Burden
HOUSTON — A new analysis highlights the high burden of insomnia across the Americas, with about 17% of adults suffering from this chronic sleep disorder.
“Our findings underscore the urgent need for enhanced clinical care pathways and policy interventions to effectively diagnose and treat insomnia. It is crucial to foster greater awareness of the critical role that sleep plays in overall health,” lead investigator Adam Benjafield, PhD, vice president for medical affairs at ResMed, Sydney, Australia, said in an interview.
“Insomnia not only affects individuals’ health and quality of life but also has broader implications for public health systems. Developing comprehensive care strategies and promoting education about sleep health could significantly improve outcomes for individuals suffering from insomnia disorder,” Dr. Benjafield said.
The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Underdiagnosed, Undertreated
Sleep disruptions contribute to various medical problems, including cognitive impairment, reduced immune function, metabolic imbalance, and exacerbation of psychiatric conditions. While the prevalence of insomnia in developed countries like the United States and Canada is known, there is limited epidemiologic evidence, and no reliable estimate for the disorder across the Americas — especially in low- and middle-income countries.
The researchers used published nation-specific data to estimate the prevalence of adult insomnia disorder across the 55 countries defined by the United Nations as comprising the Americas.
Based on the available data, the researchers estimated that about 123 million adults across the Americas have insomnia disorder (16.8%) — with greater prevalence in women (73 million, 19.5%) than in men (50 million, 14%).
The nations with the greatest burden of insomnia disorder are the United States (37 million), Brazil (29 million), and Mexico (16 million).
“While our study did not specifically investigate trends over time due to its scope, evidence from other research suggests that insomnia is becoming more prevalent over the long term. This growing trend highlights the increasing need for awareness and intervention in managing sleep health,” Dr. Benjafield said.
Insomnia is underdiagnosed and undertreated partly because of general lack of awareness about the importance of addressing sleep disorders and the fact that cognitive-behavioral therapy for insomnia (CBT-I), which is recommended as first-line treatment, is not widely accessible because of a shortage of trained CBT-I practitioners.
“Many individuals with insomnia struggle to find and receive this effective nonpharmacological treatment. Consequently, there is an overreliance on pharmaceutical solutions, which are ideally used for short-term management but are often extended due to the lack of alternatives. These medications can lead to dependency and other side effects,” Dr. Benjafield said.
Ask About Sleep
Insomnia symptoms are a “common presenting complaint in doctors’ offices in the United States. The percentages in this poster show that insomnia disorder has a similar, high percent prevalence across countries in the Americas,” Boris Gilyadov, MD, assistant professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview.
“During preventive care visits and general physical exams, patients should be asked about the quality of their sleep. Patients may benefit from a referral to the sleep medicine clinic when appropriate,” said Dr. Gilyadov, who wasn’t involved in the study.
“CBT-I is the first-line treatment for chronic insomnia disorder and can be an effective treatment for most patients. An alternative to CBT-I, when it is not available, is digital CBT-I,” Dr. Gilyadov said.
“There are also behavioral therapies called BBT-I [brief behavioral treatment for insomnia] and ACT [acceptance and commitment therapy]. These are therapies that may be offered by psychologists who specialize in the treatment of chronic insomnia disorder,” Dr. Gilyadov noted.
The study was conducted in collaboration with medXcloud and funded by ResMed. Dr. Benjafield is an employee of ResMed. Dr. Gilyadov had no relevant disclosures.
A version of this article first appeared on Medscape.com.
HOUSTON — A new analysis highlights the high burden of insomnia across the Americas, with about 17% of adults suffering from this chronic sleep disorder.
“Our findings underscore the urgent need for enhanced clinical care pathways and policy interventions to effectively diagnose and treat insomnia. It is crucial to foster greater awareness of the critical role that sleep plays in overall health,” lead investigator Adam Benjafield, PhD, vice president for medical affairs at ResMed, Sydney, Australia, said in an interview.
“Insomnia not only affects individuals’ health and quality of life but also has broader implications for public health systems. Developing comprehensive care strategies and promoting education about sleep health could significantly improve outcomes for individuals suffering from insomnia disorder,” Dr. Benjafield said.
The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Underdiagnosed, Undertreated
Sleep disruptions contribute to various medical problems, including cognitive impairment, reduced immune function, metabolic imbalance, and exacerbation of psychiatric conditions. While the prevalence of insomnia in developed countries like the United States and Canada is known, there is limited epidemiologic evidence, and no reliable estimate for the disorder across the Americas — especially in low- and middle-income countries.
The researchers used published nation-specific data to estimate the prevalence of adult insomnia disorder across the 55 countries defined by the United Nations as comprising the Americas.
Based on the available data, the researchers estimated that about 123 million adults across the Americas have insomnia disorder (16.8%) — with greater prevalence in women (73 million, 19.5%) than in men (50 million, 14%).
The nations with the greatest burden of insomnia disorder are the United States (37 million), Brazil (29 million), and Mexico (16 million).
“While our study did not specifically investigate trends over time due to its scope, evidence from other research suggests that insomnia is becoming more prevalent over the long term. This growing trend highlights the increasing need for awareness and intervention in managing sleep health,” Dr. Benjafield said.
Insomnia is underdiagnosed and undertreated partly because of general lack of awareness about the importance of addressing sleep disorders and the fact that cognitive-behavioral therapy for insomnia (CBT-I), which is recommended as first-line treatment, is not widely accessible because of a shortage of trained CBT-I practitioners.
“Many individuals with insomnia struggle to find and receive this effective nonpharmacological treatment. Consequently, there is an overreliance on pharmaceutical solutions, which are ideally used for short-term management but are often extended due to the lack of alternatives. These medications can lead to dependency and other side effects,” Dr. Benjafield said.
Ask About Sleep
Insomnia symptoms are a “common presenting complaint in doctors’ offices in the United States. The percentages in this poster show that insomnia disorder has a similar, high percent prevalence across countries in the Americas,” Boris Gilyadov, MD, assistant professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview.
“During preventive care visits and general physical exams, patients should be asked about the quality of their sleep. Patients may benefit from a referral to the sleep medicine clinic when appropriate,” said Dr. Gilyadov, who wasn’t involved in the study.
“CBT-I is the first-line treatment for chronic insomnia disorder and can be an effective treatment for most patients. An alternative to CBT-I, when it is not available, is digital CBT-I,” Dr. Gilyadov said.
“There are also behavioral therapies called BBT-I [brief behavioral treatment for insomnia] and ACT [acceptance and commitment therapy]. These are therapies that may be offered by psychologists who specialize in the treatment of chronic insomnia disorder,” Dr. Gilyadov noted.
The study was conducted in collaboration with medXcloud and funded by ResMed. Dr. Benjafield is an employee of ResMed. Dr. Gilyadov had no relevant disclosures.
A version of this article first appeared on Medscape.com.
HOUSTON — A new analysis highlights the high burden of insomnia across the Americas, with about 17% of adults suffering from this chronic sleep disorder.
“Our findings underscore the urgent need for enhanced clinical care pathways and policy interventions to effectively diagnose and treat insomnia. It is crucial to foster greater awareness of the critical role that sleep plays in overall health,” lead investigator Adam Benjafield, PhD, vice president for medical affairs at ResMed, Sydney, Australia, said in an interview.
“Insomnia not only affects individuals’ health and quality of life but also has broader implications for public health systems. Developing comprehensive care strategies and promoting education about sleep health could significantly improve outcomes for individuals suffering from insomnia disorder,” Dr. Benjafield said.
The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Underdiagnosed, Undertreated
Sleep disruptions contribute to various medical problems, including cognitive impairment, reduced immune function, metabolic imbalance, and exacerbation of psychiatric conditions. While the prevalence of insomnia in developed countries like the United States and Canada is known, there is limited epidemiologic evidence, and no reliable estimate for the disorder across the Americas — especially in low- and middle-income countries.
The researchers used published nation-specific data to estimate the prevalence of adult insomnia disorder across the 55 countries defined by the United Nations as comprising the Americas.
Based on the available data, the researchers estimated that about 123 million adults across the Americas have insomnia disorder (16.8%) — with greater prevalence in women (73 million, 19.5%) than in men (50 million, 14%).
The nations with the greatest burden of insomnia disorder are the United States (37 million), Brazil (29 million), and Mexico (16 million).
“While our study did not specifically investigate trends over time due to its scope, evidence from other research suggests that insomnia is becoming more prevalent over the long term. This growing trend highlights the increasing need for awareness and intervention in managing sleep health,” Dr. Benjafield said.
Insomnia is underdiagnosed and undertreated partly because of general lack of awareness about the importance of addressing sleep disorders and the fact that cognitive-behavioral therapy for insomnia (CBT-I), which is recommended as first-line treatment, is not widely accessible because of a shortage of trained CBT-I practitioners.
“Many individuals with insomnia struggle to find and receive this effective nonpharmacological treatment. Consequently, there is an overreliance on pharmaceutical solutions, which are ideally used for short-term management but are often extended due to the lack of alternatives. These medications can lead to dependency and other side effects,” Dr. Benjafield said.
Ask About Sleep
Insomnia symptoms are a “common presenting complaint in doctors’ offices in the United States. The percentages in this poster show that insomnia disorder has a similar, high percent prevalence across countries in the Americas,” Boris Gilyadov, MD, assistant professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview.
“During preventive care visits and general physical exams, patients should be asked about the quality of their sleep. Patients may benefit from a referral to the sleep medicine clinic when appropriate,” said Dr. Gilyadov, who wasn’t involved in the study.
“CBT-I is the first-line treatment for chronic insomnia disorder and can be an effective treatment for most patients. An alternative to CBT-I, when it is not available, is digital CBT-I,” Dr. Gilyadov said.
“There are also behavioral therapies called BBT-I [brief behavioral treatment for insomnia] and ACT [acceptance and commitment therapy]. These are therapies that may be offered by psychologists who specialize in the treatment of chronic insomnia disorder,” Dr. Gilyadov noted.
The study was conducted in collaboration with medXcloud and funded by ResMed. Dr. Benjafield is an employee of ResMed. Dr. Gilyadov had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SLEEP 2024
Intensive Lifestyle Changes May Counter Early Alzheimer’s Symptoms
, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.
Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
Study Methodology
Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.
Two patients, both in the treatment group, withdrew over logistical concerns.
After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:
- Clinical Global Impression of Change (CGIC, P = .001)
- Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
- Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
- Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)
The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.
In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
Caveats
Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.
Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.
Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
Further Study
The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.
Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.
“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”
Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field.
, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.
Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
Study Methodology
Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.
Two patients, both in the treatment group, withdrew over logistical concerns.
After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:
- Clinical Global Impression of Change (CGIC, P = .001)
- Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
- Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
- Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)
The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.
In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
Caveats
Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.
Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.
Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
Further Study
The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.
Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.
“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”
Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field.
, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.
Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
Study Methodology
Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.
Two patients, both in the treatment group, withdrew over logistical concerns.
After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:
- Clinical Global Impression of Change (CGIC, P = .001)
- Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
- Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
- Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)
The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.
In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
Caveats
Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.
Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.
Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
Further Study
The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.
Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.
“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”
Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field.
FROM ALZHEIMER’S RESEARCH & THERAPY
Intensive Interventions Are Needed for High-BMI Youth
The U.S. Preventive Services Task Force (USPSTF) is recommending that clinicians provide comprehensive, intensive behavioral interventions for children 6 years and older who have a high body mass index (BMI) at or above the 95th percentile (for age and sex) or refer those patients to an appropriate provider.
One in five children (19.7%) and adolescents ages 2-19 in the United States are at or above this range, based on Centers for Disease Control and Prevention growth charts from 2000, the task force wrote in its statement. The rate of BMI increase nearly doubled in this age group during the COVID pandemic, compared with prepandemic levels.
Publishing their recommendations in JAMA, the task force, with lead author Wanda K. Nicholson, MD, MPH, MBA, with the Milken Institute of Public Health, George Washington University, Washington, D.C., also noted that the prevalence of high BMI increases with age and rates are higher among children from lower-income families. Rates are also higher in Hispanic/Latino, Native American/Alaska Native and non-Hispanic Black children.
At Least 26 Hours of Interventions
It is important that children and adolescents 6 years or older with a high BMI receive intensive interventions for at least 26 contact hours for up to a year, as evidence showed that was the threshold for weight loss, the task force said.
Based on its evidence review, the USPSTF assigned this recommendation a B grade indicating “moderate certainty ... of moderate net benefit.” The task force analyzed 50 randomized clinical trials (RCTs) (n = 8,798) that examined behavioral interventions. They also analyzed eight trials that assessed pharmacotherapy interventions: liraglutide (three RCTs), semaglutide (one RCT), orlistat (two RCTs) and phentermine/topiramate (two RCTs). Five trials included behavioral counseling with the medication or placebo.
These new recommendations also reaffirm the task force’s 2010 and 2023 recommendations.
Effective interventions had multiple components. They included interventions targeting both the parent and child (separately, together or both); group sessions; information about healthy eating, information on reading food labels, and safe exercising; and interventions for encouraging behavioral changes, such as monitoring food intake and problem solving, changing physical activity behaviors, and goal setting.
These types of interventions are often delivered by multidisciplinary teams, including pediatricians, exercise physiologists or physical therapists, dietitians, psychologists, social workers, or other behavioral specialists.
Personalizing Treatment for Optimal Benefit
“The time to prevent and intervene on childhood obesity is now, and the need to start with ILT [intensive lifestyle therapy] is clear,” Roohi Y. Kharofa, MD, with the department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, and colleagues wrote in a related editorial.
However, the editorialists noted it will be important to personalize the level of interventions as ILT won’t be enough for some to prevent serious outcomes. For such patients, bariatric surgery or pharmacotherapy may need to be considered as well.
Ways to Reach the 26 Hours
Dr. Kharofa and coauthors pointed out that, while the threshold of at least 26 contact hours is associated with significant improvement in BMI (mean BMI difference, –0.8; 95% CI, –1.2 to –0.4), and while it’s important to now have an evidence-based threshold, the number may be disheartening given limits on clinicians, staff, and resources. The key may be prescribing physical activity sessions outside the health system.
For patients not interested in group sports or burdened by participation fees, collaboration with local community organizations, such as the YMCA or the Boys & Girls Club, could be arranged, the authors suggested.
“The inability to attain 26 hours should not deter patients or practitioners from participating in, referring to, or implementing obesity interventions. Rather, clinical teams and families should work together to maximize intervention dose using clinical and community programs synergistically,” they wrote.
They noted that the USPSTF in this 2024 update found “inadequate evidence on the benefits of pharmacotherapy in youth with obesity, encouraging clinicians to use ILT as the primary intervention.”
What About Medications?
New since the previous USPSTF review, several new medications have been approved for weight loss in pediatric populations, Elizabeth A. O’Connor, PhD, with The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, and colleagues noted in their updated evidence report.
They noted that the 2023 Clinical Practice Guideline developed by the American Academy of Pediatrics states that clinicians “may offer children ages 8 through 11 years of age with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment.”
However, Dr. O’Connor and coauthors wrote, the evidence base for each agent is limited and there is no information in the literature supporting their findings on harms of medication use beyond 17 months.
“For pharmacotherapy, when evidence was available on weight maintenance after discontinuation, weight rebounded quickly after medication use ended,” the authors wrote. “This suggests that long-term use is required for weight maintenance and underscores the need for evidence about potential harms from long-term use.”
Changes in Investment, Food, Government Priorities Are Needed
In a separate accompanying editorial, Thomas N. Robinson, MD, MPH, with Stanford University’s Center for Healthy Weight and General Pediatrics Department in Palo Alto, California, and Sarah C. Armstrong, MD, with the Duke Center for Childhood Obesity Research, Chapel Hill, North Carolina, wrote that experience to date has shown that current approaches aren’t working and, in fact, pediatric obesity rates are worsening.
“After nearly 15 years of authoritative, evidence-backed USPSTF recommendations for effective interventions for children with high BMI, it is long past time to implement them,” they wrote.
But changes will need to go far beyond clinicians’ offices and priorities must change at local, state, and federal levels, Dr. Robinson and Dr. Armstrong wrote. A shift in priorities is needed to make screening and behavioral interventions available to all children and teens with obesity.
Public policies, they wrote, must address larger issues, such as food content and availability of healthy foods, transportation innovations, and ways to make active lifestyles available equitably.
The authors said that strategies may include taxing sugary drinks, regulating marketing of unhealthful foods, crafting legislation to regulate the nutritional content of school meals, and creating policies to reduce poverty and address social drivers of health.
“A synergistic combination of effective clinical care, as recommended by the USPSTF, and public policy interventions is critically needed to turn the tide on childhood obesity,” Dr. Robinson and Dr. Armstrong wrote.
The full recommendation statement is available at the USPSTF website or the JAMA website.
One coauthor of the recommendation statement reported receiving publications and federal grand funding to his institution for the relationship between obesity and the potential effect of nutrition policy interventions on cardiovascular disease and cancer and for a meta-analysis of the effect of dietary counseling for weight loss. The authors of the evidence report had no relevant conflicts of interest. Dr. Kharofa reported receiving grants from Rhythm Pharmaceuticals outside the submitted work. Dr. Robinson has served on the scientific advisory board of WW International (through December 2022). Dr. Armstrong has served as chair of the Section on Obesity, American Academy of Pediatrics; and is a coauthor of the Clinical Practice Guidelines for the Evaluation and Treatment of Children and Adolescents with Obesity.
The U.S. Preventive Services Task Force (USPSTF) is recommending that clinicians provide comprehensive, intensive behavioral interventions for children 6 years and older who have a high body mass index (BMI) at or above the 95th percentile (for age and sex) or refer those patients to an appropriate provider.
One in five children (19.7%) and adolescents ages 2-19 in the United States are at or above this range, based on Centers for Disease Control and Prevention growth charts from 2000, the task force wrote in its statement. The rate of BMI increase nearly doubled in this age group during the COVID pandemic, compared with prepandemic levels.
Publishing their recommendations in JAMA, the task force, with lead author Wanda K. Nicholson, MD, MPH, MBA, with the Milken Institute of Public Health, George Washington University, Washington, D.C., also noted that the prevalence of high BMI increases with age and rates are higher among children from lower-income families. Rates are also higher in Hispanic/Latino, Native American/Alaska Native and non-Hispanic Black children.
At Least 26 Hours of Interventions
It is important that children and adolescents 6 years or older with a high BMI receive intensive interventions for at least 26 contact hours for up to a year, as evidence showed that was the threshold for weight loss, the task force said.
Based on its evidence review, the USPSTF assigned this recommendation a B grade indicating “moderate certainty ... of moderate net benefit.” The task force analyzed 50 randomized clinical trials (RCTs) (n = 8,798) that examined behavioral interventions. They also analyzed eight trials that assessed pharmacotherapy interventions: liraglutide (three RCTs), semaglutide (one RCT), orlistat (two RCTs) and phentermine/topiramate (two RCTs). Five trials included behavioral counseling with the medication or placebo.
These new recommendations also reaffirm the task force’s 2010 and 2023 recommendations.
Effective interventions had multiple components. They included interventions targeting both the parent and child (separately, together or both); group sessions; information about healthy eating, information on reading food labels, and safe exercising; and interventions for encouraging behavioral changes, such as monitoring food intake and problem solving, changing physical activity behaviors, and goal setting.
These types of interventions are often delivered by multidisciplinary teams, including pediatricians, exercise physiologists or physical therapists, dietitians, psychologists, social workers, or other behavioral specialists.
Personalizing Treatment for Optimal Benefit
“The time to prevent and intervene on childhood obesity is now, and the need to start with ILT [intensive lifestyle therapy] is clear,” Roohi Y. Kharofa, MD, with the department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, and colleagues wrote in a related editorial.
However, the editorialists noted it will be important to personalize the level of interventions as ILT won’t be enough for some to prevent serious outcomes. For such patients, bariatric surgery or pharmacotherapy may need to be considered as well.
Ways to Reach the 26 Hours
Dr. Kharofa and coauthors pointed out that, while the threshold of at least 26 contact hours is associated with significant improvement in BMI (mean BMI difference, –0.8; 95% CI, –1.2 to –0.4), and while it’s important to now have an evidence-based threshold, the number may be disheartening given limits on clinicians, staff, and resources. The key may be prescribing physical activity sessions outside the health system.
For patients not interested in group sports or burdened by participation fees, collaboration with local community organizations, such as the YMCA or the Boys & Girls Club, could be arranged, the authors suggested.
“The inability to attain 26 hours should not deter patients or practitioners from participating in, referring to, or implementing obesity interventions. Rather, clinical teams and families should work together to maximize intervention dose using clinical and community programs synergistically,” they wrote.
They noted that the USPSTF in this 2024 update found “inadequate evidence on the benefits of pharmacotherapy in youth with obesity, encouraging clinicians to use ILT as the primary intervention.”
What About Medications?
New since the previous USPSTF review, several new medications have been approved for weight loss in pediatric populations, Elizabeth A. O’Connor, PhD, with The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, and colleagues noted in their updated evidence report.
They noted that the 2023 Clinical Practice Guideline developed by the American Academy of Pediatrics states that clinicians “may offer children ages 8 through 11 years of age with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment.”
However, Dr. O’Connor and coauthors wrote, the evidence base for each agent is limited and there is no information in the literature supporting their findings on harms of medication use beyond 17 months.
“For pharmacotherapy, when evidence was available on weight maintenance after discontinuation, weight rebounded quickly after medication use ended,” the authors wrote. “This suggests that long-term use is required for weight maintenance and underscores the need for evidence about potential harms from long-term use.”
Changes in Investment, Food, Government Priorities Are Needed
In a separate accompanying editorial, Thomas N. Robinson, MD, MPH, with Stanford University’s Center for Healthy Weight and General Pediatrics Department in Palo Alto, California, and Sarah C. Armstrong, MD, with the Duke Center for Childhood Obesity Research, Chapel Hill, North Carolina, wrote that experience to date has shown that current approaches aren’t working and, in fact, pediatric obesity rates are worsening.
“After nearly 15 years of authoritative, evidence-backed USPSTF recommendations for effective interventions for children with high BMI, it is long past time to implement them,” they wrote.
But changes will need to go far beyond clinicians’ offices and priorities must change at local, state, and federal levels, Dr. Robinson and Dr. Armstrong wrote. A shift in priorities is needed to make screening and behavioral interventions available to all children and teens with obesity.
Public policies, they wrote, must address larger issues, such as food content and availability of healthy foods, transportation innovations, and ways to make active lifestyles available equitably.
The authors said that strategies may include taxing sugary drinks, regulating marketing of unhealthful foods, crafting legislation to regulate the nutritional content of school meals, and creating policies to reduce poverty and address social drivers of health.
“A synergistic combination of effective clinical care, as recommended by the USPSTF, and public policy interventions is critically needed to turn the tide on childhood obesity,” Dr. Robinson and Dr. Armstrong wrote.
The full recommendation statement is available at the USPSTF website or the JAMA website.
One coauthor of the recommendation statement reported receiving publications and federal grand funding to his institution for the relationship between obesity and the potential effect of nutrition policy interventions on cardiovascular disease and cancer and for a meta-analysis of the effect of dietary counseling for weight loss. The authors of the evidence report had no relevant conflicts of interest. Dr. Kharofa reported receiving grants from Rhythm Pharmaceuticals outside the submitted work. Dr. Robinson has served on the scientific advisory board of WW International (through December 2022). Dr. Armstrong has served as chair of the Section on Obesity, American Academy of Pediatrics; and is a coauthor of the Clinical Practice Guidelines for the Evaluation and Treatment of Children and Adolescents with Obesity.
The U.S. Preventive Services Task Force (USPSTF) is recommending that clinicians provide comprehensive, intensive behavioral interventions for children 6 years and older who have a high body mass index (BMI) at or above the 95th percentile (for age and sex) or refer those patients to an appropriate provider.
One in five children (19.7%) and adolescents ages 2-19 in the United States are at or above this range, based on Centers for Disease Control and Prevention growth charts from 2000, the task force wrote in its statement. The rate of BMI increase nearly doubled in this age group during the COVID pandemic, compared with prepandemic levels.
Publishing their recommendations in JAMA, the task force, with lead author Wanda K. Nicholson, MD, MPH, MBA, with the Milken Institute of Public Health, George Washington University, Washington, D.C., also noted that the prevalence of high BMI increases with age and rates are higher among children from lower-income families. Rates are also higher in Hispanic/Latino, Native American/Alaska Native and non-Hispanic Black children.
At Least 26 Hours of Interventions
It is important that children and adolescents 6 years or older with a high BMI receive intensive interventions for at least 26 contact hours for up to a year, as evidence showed that was the threshold for weight loss, the task force said.
Based on its evidence review, the USPSTF assigned this recommendation a B grade indicating “moderate certainty ... of moderate net benefit.” The task force analyzed 50 randomized clinical trials (RCTs) (n = 8,798) that examined behavioral interventions. They also analyzed eight trials that assessed pharmacotherapy interventions: liraglutide (three RCTs), semaglutide (one RCT), orlistat (two RCTs) and phentermine/topiramate (two RCTs). Five trials included behavioral counseling with the medication or placebo.
These new recommendations also reaffirm the task force’s 2010 and 2023 recommendations.
Effective interventions had multiple components. They included interventions targeting both the parent and child (separately, together or both); group sessions; information about healthy eating, information on reading food labels, and safe exercising; and interventions for encouraging behavioral changes, such as monitoring food intake and problem solving, changing physical activity behaviors, and goal setting.
These types of interventions are often delivered by multidisciplinary teams, including pediatricians, exercise physiologists or physical therapists, dietitians, psychologists, social workers, or other behavioral specialists.
Personalizing Treatment for Optimal Benefit
“The time to prevent and intervene on childhood obesity is now, and the need to start with ILT [intensive lifestyle therapy] is clear,” Roohi Y. Kharofa, MD, with the department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, and colleagues wrote in a related editorial.
However, the editorialists noted it will be important to personalize the level of interventions as ILT won’t be enough for some to prevent serious outcomes. For such patients, bariatric surgery or pharmacotherapy may need to be considered as well.
Ways to Reach the 26 Hours
Dr. Kharofa and coauthors pointed out that, while the threshold of at least 26 contact hours is associated with significant improvement in BMI (mean BMI difference, –0.8; 95% CI, –1.2 to –0.4), and while it’s important to now have an evidence-based threshold, the number may be disheartening given limits on clinicians, staff, and resources. The key may be prescribing physical activity sessions outside the health system.
For patients not interested in group sports or burdened by participation fees, collaboration with local community organizations, such as the YMCA or the Boys & Girls Club, could be arranged, the authors suggested.
“The inability to attain 26 hours should not deter patients or practitioners from participating in, referring to, or implementing obesity interventions. Rather, clinical teams and families should work together to maximize intervention dose using clinical and community programs synergistically,” they wrote.
They noted that the USPSTF in this 2024 update found “inadequate evidence on the benefits of pharmacotherapy in youth with obesity, encouraging clinicians to use ILT as the primary intervention.”
What About Medications?
New since the previous USPSTF review, several new medications have been approved for weight loss in pediatric populations, Elizabeth A. O’Connor, PhD, with The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, and colleagues noted in their updated evidence report.
They noted that the 2023 Clinical Practice Guideline developed by the American Academy of Pediatrics states that clinicians “may offer children ages 8 through 11 years of age with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment.”
However, Dr. O’Connor and coauthors wrote, the evidence base for each agent is limited and there is no information in the literature supporting their findings on harms of medication use beyond 17 months.
“For pharmacotherapy, when evidence was available on weight maintenance after discontinuation, weight rebounded quickly after medication use ended,” the authors wrote. “This suggests that long-term use is required for weight maintenance and underscores the need for evidence about potential harms from long-term use.”
Changes in Investment, Food, Government Priorities Are Needed
In a separate accompanying editorial, Thomas N. Robinson, MD, MPH, with Stanford University’s Center for Healthy Weight and General Pediatrics Department in Palo Alto, California, and Sarah C. Armstrong, MD, with the Duke Center for Childhood Obesity Research, Chapel Hill, North Carolina, wrote that experience to date has shown that current approaches aren’t working and, in fact, pediatric obesity rates are worsening.
“After nearly 15 years of authoritative, evidence-backed USPSTF recommendations for effective interventions for children with high BMI, it is long past time to implement them,” they wrote.
But changes will need to go far beyond clinicians’ offices and priorities must change at local, state, and federal levels, Dr. Robinson and Dr. Armstrong wrote. A shift in priorities is needed to make screening and behavioral interventions available to all children and teens with obesity.
Public policies, they wrote, must address larger issues, such as food content and availability of healthy foods, transportation innovations, and ways to make active lifestyles available equitably.
The authors said that strategies may include taxing sugary drinks, regulating marketing of unhealthful foods, crafting legislation to regulate the nutritional content of school meals, and creating policies to reduce poverty and address social drivers of health.
“A synergistic combination of effective clinical care, as recommended by the USPSTF, and public policy interventions is critically needed to turn the tide on childhood obesity,” Dr. Robinson and Dr. Armstrong wrote.
The full recommendation statement is available at the USPSTF website or the JAMA website.
One coauthor of the recommendation statement reported receiving publications and federal grand funding to his institution for the relationship between obesity and the potential effect of nutrition policy interventions on cardiovascular disease and cancer and for a meta-analysis of the effect of dietary counseling for weight loss. The authors of the evidence report had no relevant conflicts of interest. Dr. Kharofa reported receiving grants from Rhythm Pharmaceuticals outside the submitted work. Dr. Robinson has served on the scientific advisory board of WW International (through December 2022). Dr. Armstrong has served as chair of the Section on Obesity, American Academy of Pediatrics; and is a coauthor of the Clinical Practice Guidelines for the Evaluation and Treatment of Children and Adolescents with Obesity.
FROM JAMA
Updated Guideline Reflects New Drugs for Type 2 Diabetes
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Acute Sore Throat in Primary Care: When to Reach for the Antibiotics
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
Flesh-Colored Pinpoint Papules With Fine White Spicules on the Upper Body
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
A 54-year-old Black woman presented with a rash that developed 6 months after a renal transplant due to a history of systemic lupus erythematosus with lupus nephritis. She was started on mycophenolate mofetil and tacrolimus after the transplant but was switched to cyclosporine because of BK viremia. The rash developed 1 week after cyclosporine was initiated and consisted of pruritic papules that started on the face and spread to the trunk and arms. Physical examination revealed innumerable follicular-based, keratotic, flesh-colored, pinpoint papules with fine white spicules on the face (top), neck, chest, arms, and back. Leonine facies was seen along the glabella with madarosis of the lateral eyebrows (top) and ears (bottom).
