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Treating Onychomycosis: Pearls from a Podiatrist
LAS VEGAS —
According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.
“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”
Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”
How Does This Happen?
Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”
The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”
Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.
“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”
According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.
Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?
Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.
Evidence for Lasers Weak
Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”
Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”
Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.
What About Oral Antifungal Safety?
For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.
According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”
Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.
A version of this article appeared on Medscape.com.
LAS VEGAS —
According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.
“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”
Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”
How Does This Happen?
Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”
The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”
Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.
“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”
According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.
Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?
Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.
Evidence for Lasers Weak
Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”
Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”
Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.
What About Oral Antifungal Safety?
For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.
According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”
Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.
A version of this article appeared on Medscape.com.
LAS VEGAS —
According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.
“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”
Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”
How Does This Happen?
Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”
The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”
Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.
“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”
According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.
Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?
Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.
Evidence for Lasers Weak
Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”
Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”
Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.
What About Oral Antifungal Safety?
For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.
According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”
Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.
A version of this article appeared on Medscape.com.
FROM SDPA 2024
Study Finds Different Survival Rates for Hidradenitis Suppurativa Treatments in Children
results from a small single-center study showed.
A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”
Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.
To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.
The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.
On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.
The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.
“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.
The researchers reported having no financial disclosures.
A version of this article appeared on Medscape.com.
results from a small single-center study showed.
A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”
Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.
To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.
The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.
On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.
The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.
“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.
The researchers reported having no financial disclosures.
A version of this article appeared on Medscape.com.
results from a small single-center study showed.
A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”
Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.
To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.
The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.
On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.
The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.
“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.
The researchers reported having no financial disclosures.
A version of this article appeared on Medscape.com.
FROM SDPA 24
Varicella Outbreaks: 2022-2024
Practitioners providing care to children are familiar with the childhood immunization schedule and routinely administer varicella vaccine at the 12-month and 4- to 5-year visits. However, when is the last time most of us or any of the current trainees have seen a case?
Briefly, varicella is a highly contagious disease caused by varicella-zoster virus (VZV). It is characterized by a generalized pruritic erythematous rash in various stages of development beginning as macules, progressing to papules, and ultimately becoming vesicular lesions on an erythematous base (“dewdrop on a rose petal”) and resolves with crusting of the lesion (Figure 1). It has an incubation period of 10-21 days with symptoms usually developing within 14-16 days after exposure. The vesicular rash must be differentiated from enterovirus, Staphylococcus aureus, contact dermatitis, or insect bites, which initially may be difficult. Approximately 50% of children can have symptoms including fever, malaise, anorexia, headache, and occasionally, mild abdominal pain in the 24-48 hours prior to the appearance of rash. Lesions usually first appear on the scalp, face, or trunk in successive crops over several days. A person with varicella has lesions in various stages.
In a normal host, new vesicle formation usually stops within 4 days, and most lesions have fully crusted by day 6. VZV establishes latency in sensory ganglia and may reactivate years or decades later to cause herpes zoster (HZ). Most healthy children with varicella recover without sequelae so the disease is generally regarded as benign. However, varicella can lead to serious complications and deaths in healthy as well as immunocompromised persons.
Complications of Varicella: bacterial superinfection of skin lesions most often with Streptococcus pyogenes or S aureus manifested as cellulitis, myositis, or necrotizing fasciitis; neurologic complications include cerebellar ataxia and encephalitis with the latter seen most often in adults. Pneumonia occurs most often in adults, especially those infected during pregnancy. Another concern, infection during the first 20 weeks of pregnancy can lead to fetal death or severe birth defects, including limb hypoplasia, cutaneous scarring, ocular abnormalities, and central nervous system damage (congenital varicella syndrome).
The risk for development of severe disseminated disease was first noted in the 1960s as treatments for leukemia in children improved. They were surviving their cancer only to develop severe and often fatal varicella. Today it is recognized that development of disseminated disease is a risk for all infected persons with impaired T cell function, malignancies, HIV, or receiving immunosuppressive therapy.
Reye’s syndrome is rarely seen today since taking salicylates while infected with VZV was identified as a predisposing factor for development.
VZV is only found in humans and transmission is person to person or airborne. The secondary household attack rate is approximately 90%. In contrast, the secondary attack rates in classrooms may be as low as 12%-33%. Transmission rates in the tropics for unexplained reasons are also lower.
Vaccine History: Why do we rarely see this disease anymore? Varicella, a live attenuated vaccine, was developed in 1974 by Dr. Michiaki Takahashi. It remains the only vaccine directed against a herpes group virus. In 1979, the Collaborative Varicella Vaccine Study Group was established at the National Institutes of Health (NIH) and additional safety and efficacy trials were conducted in the United States initially in leukemic patients in remission and later in healthy children, which supported Takahashi’s data. Licensure of varicella vaccine was granted in 1995. That same year, due to continuing disease and societal burden, the United States was the first country to incorporate varicella into the routine childhood immunization schedule, which resulted in significant reductions in cases. To further improve control of varicella, in 2007 vaccine recommendations were revised and a routine two-dose schedule was implemented. The impact of varicella disease pre- and post-vaccine licensure is illustrated in Figure 2. Not listed, is that in the pre-vaccine era, there were approximately 44 cases of congenital varicella syndrome annually.
As of 2023 only 23% (45/195) of nations routinely administer this vaccine and 4% (8/195) have restricted recommendations. The remaining 73% of countries do not offer the vaccine, including all countries on the African continent, and Cuba, Guatemala, Haiti, Honduras, India, Jordan, Lebanon, Philippines, Portugal, and Venezuela to list a few.
Varicella Outbreak: In October 2022, New York City (NYC) identified a varicella outbreak primarily involving persons who recently migrated from Central and South America and lived in a shelter in NYC or residential facility (n = 105); the outbreak is ongoing. As of March 8, 2024, 873 cases (53%) were among children aged 4-18 years and 91.9% had no documentation of varicella vaccine at time of symptom onset. There were 28 hospitalizations, and no deaths reported. The most common sources of transmission were the residential facilities (41.3%) and importation or possible importation (39.4%). School transmission accounted for only 1.2% of cases.
Most migrants arrived from countries where varicella vaccination is not part of the routine childhood immunization schedule. Although most cases occurred in children, almost 30% occurred in adults. Many of the migrants arrived from tropical countries where susceptibility rates are also higher in adults. This outbreak is a reminder of the importance of limiting disease transmission by maintaining high vaccination rates. To curtail this outbreak, approximately 27,000 doses of varicella vaccine were administered to the arriving migrants. In addition, MMR, COVID-19, influenza, and all routine pediatric vaccines required for school entry were administered. Temporary closure of the residential facilities were required. Education was provided to residents regarding immunizations as well as assistance to help them establish a primary care home. Multiple agencies were mobilized to successfully coordinate these efforts.
Take Home Message
1. Each country has its own routine immunization schedule. It may not include all vaccines recommended in the US schedule. When questioned I’m frequently told that immunizations are up to date, only to review records and find they are not, especially when it is related to MMR. It is often administered at 9 months and/or MR or MM is administered depending on the country. As reported here, varicella is a routine vaccine in only 45 countries.
2.
3. Once an outbreak has been identified, the infrastructure to manage and contain it must already be established. In most instances there will be a need for a rapid and often large-scale effort involving multiple agencies including local health care providers.
4. Not all diseases are reportable. Only deaths by varicella are nationally notifiable. Otherwise, cases are reported voluntarily. As of November 2, 2024, there have been 5,157 cases of varicella reported, excluding any cases from NYC.
Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
Suggested Reading
CDC. Nationally Notifiable Infectious Diseases and Conditions, United States: Weekly Tables. https://wonder.cdc.gov/nndss/nndss_weekly_tables_menu.asp.
Graham KA et al. Varicella Outbreak Among Recent Arrivals to New York City, 2022-2024. MMWR Morb Mortal Wkly Rep. 2024 May 30;73(21):478-483. doi: 10.15585/mmwr.mm7321a1.
Marin M et al. Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020. J Infect Dis. 2022 Oct 21;226(Suppl 4):S463-S469. doi: 10.1093/infdis/jiac271.
Varicella-Zoster Virus Infections in Kimberkin DW et al, eds. Red Book: 2024 Report of the Committee on Infectious Diseases, 33rd Edition. American Academy of Pediatrics, 2024:938-951. https://www.aap.org/Red-Book-2024-Report-of-the-Committee-on-Infectious-Diseases-33rd-Edition-Paperback?srsltid=AfmBOoqyF60rR9ZwQ5jA8AouNhtRRTyPLnc_r7HWw7JVYV8v33Hr2vQS.
Practitioners providing care to children are familiar with the childhood immunization schedule and routinely administer varicella vaccine at the 12-month and 4- to 5-year visits. However, when is the last time most of us or any of the current trainees have seen a case?
Briefly, varicella is a highly contagious disease caused by varicella-zoster virus (VZV). It is characterized by a generalized pruritic erythematous rash in various stages of development beginning as macules, progressing to papules, and ultimately becoming vesicular lesions on an erythematous base (“dewdrop on a rose petal”) and resolves with crusting of the lesion (Figure 1). It has an incubation period of 10-21 days with symptoms usually developing within 14-16 days after exposure. The vesicular rash must be differentiated from enterovirus, Staphylococcus aureus, contact dermatitis, or insect bites, which initially may be difficult. Approximately 50% of children can have symptoms including fever, malaise, anorexia, headache, and occasionally, mild abdominal pain in the 24-48 hours prior to the appearance of rash. Lesions usually first appear on the scalp, face, or trunk in successive crops over several days. A person with varicella has lesions in various stages.
In a normal host, new vesicle formation usually stops within 4 days, and most lesions have fully crusted by day 6. VZV establishes latency in sensory ganglia and may reactivate years or decades later to cause herpes zoster (HZ). Most healthy children with varicella recover without sequelae so the disease is generally regarded as benign. However, varicella can lead to serious complications and deaths in healthy as well as immunocompromised persons.
Complications of Varicella: bacterial superinfection of skin lesions most often with Streptococcus pyogenes or S aureus manifested as cellulitis, myositis, or necrotizing fasciitis; neurologic complications include cerebellar ataxia and encephalitis with the latter seen most often in adults. Pneumonia occurs most often in adults, especially those infected during pregnancy. Another concern, infection during the first 20 weeks of pregnancy can lead to fetal death or severe birth defects, including limb hypoplasia, cutaneous scarring, ocular abnormalities, and central nervous system damage (congenital varicella syndrome).
The risk for development of severe disseminated disease was first noted in the 1960s as treatments for leukemia in children improved. They were surviving their cancer only to develop severe and often fatal varicella. Today it is recognized that development of disseminated disease is a risk for all infected persons with impaired T cell function, malignancies, HIV, or receiving immunosuppressive therapy.
Reye’s syndrome is rarely seen today since taking salicylates while infected with VZV was identified as a predisposing factor for development.
VZV is only found in humans and transmission is person to person or airborne. The secondary household attack rate is approximately 90%. In contrast, the secondary attack rates in classrooms may be as low as 12%-33%. Transmission rates in the tropics for unexplained reasons are also lower.
Vaccine History: Why do we rarely see this disease anymore? Varicella, a live attenuated vaccine, was developed in 1974 by Dr. Michiaki Takahashi. It remains the only vaccine directed against a herpes group virus. In 1979, the Collaborative Varicella Vaccine Study Group was established at the National Institutes of Health (NIH) and additional safety and efficacy trials were conducted in the United States initially in leukemic patients in remission and later in healthy children, which supported Takahashi’s data. Licensure of varicella vaccine was granted in 1995. That same year, due to continuing disease and societal burden, the United States was the first country to incorporate varicella into the routine childhood immunization schedule, which resulted in significant reductions in cases. To further improve control of varicella, in 2007 vaccine recommendations were revised and a routine two-dose schedule was implemented. The impact of varicella disease pre- and post-vaccine licensure is illustrated in Figure 2. Not listed, is that in the pre-vaccine era, there were approximately 44 cases of congenital varicella syndrome annually.
As of 2023 only 23% (45/195) of nations routinely administer this vaccine and 4% (8/195) have restricted recommendations. The remaining 73% of countries do not offer the vaccine, including all countries on the African continent, and Cuba, Guatemala, Haiti, Honduras, India, Jordan, Lebanon, Philippines, Portugal, and Venezuela to list a few.
Varicella Outbreak: In October 2022, New York City (NYC) identified a varicella outbreak primarily involving persons who recently migrated from Central and South America and lived in a shelter in NYC or residential facility (n = 105); the outbreak is ongoing. As of March 8, 2024, 873 cases (53%) were among children aged 4-18 years and 91.9% had no documentation of varicella vaccine at time of symptom onset. There were 28 hospitalizations, and no deaths reported. The most common sources of transmission were the residential facilities (41.3%) and importation or possible importation (39.4%). School transmission accounted for only 1.2% of cases.
Most migrants arrived from countries where varicella vaccination is not part of the routine childhood immunization schedule. Although most cases occurred in children, almost 30% occurred in adults. Many of the migrants arrived from tropical countries where susceptibility rates are also higher in adults. This outbreak is a reminder of the importance of limiting disease transmission by maintaining high vaccination rates. To curtail this outbreak, approximately 27,000 doses of varicella vaccine were administered to the arriving migrants. In addition, MMR, COVID-19, influenza, and all routine pediatric vaccines required for school entry were administered. Temporary closure of the residential facilities were required. Education was provided to residents regarding immunizations as well as assistance to help them establish a primary care home. Multiple agencies were mobilized to successfully coordinate these efforts.
Take Home Message
1. Each country has its own routine immunization schedule. It may not include all vaccines recommended in the US schedule. When questioned I’m frequently told that immunizations are up to date, only to review records and find they are not, especially when it is related to MMR. It is often administered at 9 months and/or MR or MM is administered depending on the country. As reported here, varicella is a routine vaccine in only 45 countries.
2.
3. Once an outbreak has been identified, the infrastructure to manage and contain it must already be established. In most instances there will be a need for a rapid and often large-scale effort involving multiple agencies including local health care providers.
4. Not all diseases are reportable. Only deaths by varicella are nationally notifiable. Otherwise, cases are reported voluntarily. As of November 2, 2024, there have been 5,157 cases of varicella reported, excluding any cases from NYC.
Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
Suggested Reading
CDC. Nationally Notifiable Infectious Diseases and Conditions, United States: Weekly Tables. https://wonder.cdc.gov/nndss/nndss_weekly_tables_menu.asp.
Graham KA et al. Varicella Outbreak Among Recent Arrivals to New York City, 2022-2024. MMWR Morb Mortal Wkly Rep. 2024 May 30;73(21):478-483. doi: 10.15585/mmwr.mm7321a1.
Marin M et al. Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020. J Infect Dis. 2022 Oct 21;226(Suppl 4):S463-S469. doi: 10.1093/infdis/jiac271.
Varicella-Zoster Virus Infections in Kimberkin DW et al, eds. Red Book: 2024 Report of the Committee on Infectious Diseases, 33rd Edition. American Academy of Pediatrics, 2024:938-951. https://www.aap.org/Red-Book-2024-Report-of-the-Committee-on-Infectious-Diseases-33rd-Edition-Paperback?srsltid=AfmBOoqyF60rR9ZwQ5jA8AouNhtRRTyPLnc_r7HWw7JVYV8v33Hr2vQS.
Practitioners providing care to children are familiar with the childhood immunization schedule and routinely administer varicella vaccine at the 12-month and 4- to 5-year visits. However, when is the last time most of us or any of the current trainees have seen a case?
Briefly, varicella is a highly contagious disease caused by varicella-zoster virus (VZV). It is characterized by a generalized pruritic erythematous rash in various stages of development beginning as macules, progressing to papules, and ultimately becoming vesicular lesions on an erythematous base (“dewdrop on a rose petal”) and resolves with crusting of the lesion (Figure 1). It has an incubation period of 10-21 days with symptoms usually developing within 14-16 days after exposure. The vesicular rash must be differentiated from enterovirus, Staphylococcus aureus, contact dermatitis, or insect bites, which initially may be difficult. Approximately 50% of children can have symptoms including fever, malaise, anorexia, headache, and occasionally, mild abdominal pain in the 24-48 hours prior to the appearance of rash. Lesions usually first appear on the scalp, face, or trunk in successive crops over several days. A person with varicella has lesions in various stages.
In a normal host, new vesicle formation usually stops within 4 days, and most lesions have fully crusted by day 6. VZV establishes latency in sensory ganglia and may reactivate years or decades later to cause herpes zoster (HZ). Most healthy children with varicella recover without sequelae so the disease is generally regarded as benign. However, varicella can lead to serious complications and deaths in healthy as well as immunocompromised persons.
Complications of Varicella: bacterial superinfection of skin lesions most often with Streptococcus pyogenes or S aureus manifested as cellulitis, myositis, or necrotizing fasciitis; neurologic complications include cerebellar ataxia and encephalitis with the latter seen most often in adults. Pneumonia occurs most often in adults, especially those infected during pregnancy. Another concern, infection during the first 20 weeks of pregnancy can lead to fetal death or severe birth defects, including limb hypoplasia, cutaneous scarring, ocular abnormalities, and central nervous system damage (congenital varicella syndrome).
The risk for development of severe disseminated disease was first noted in the 1960s as treatments for leukemia in children improved. They were surviving their cancer only to develop severe and often fatal varicella. Today it is recognized that development of disseminated disease is a risk for all infected persons with impaired T cell function, malignancies, HIV, or receiving immunosuppressive therapy.
Reye’s syndrome is rarely seen today since taking salicylates while infected with VZV was identified as a predisposing factor for development.
VZV is only found in humans and transmission is person to person or airborne. The secondary household attack rate is approximately 90%. In contrast, the secondary attack rates in classrooms may be as low as 12%-33%. Transmission rates in the tropics for unexplained reasons are also lower.
Vaccine History: Why do we rarely see this disease anymore? Varicella, a live attenuated vaccine, was developed in 1974 by Dr. Michiaki Takahashi. It remains the only vaccine directed against a herpes group virus. In 1979, the Collaborative Varicella Vaccine Study Group was established at the National Institutes of Health (NIH) and additional safety and efficacy trials were conducted in the United States initially in leukemic patients in remission and later in healthy children, which supported Takahashi’s data. Licensure of varicella vaccine was granted in 1995. That same year, due to continuing disease and societal burden, the United States was the first country to incorporate varicella into the routine childhood immunization schedule, which resulted in significant reductions in cases. To further improve control of varicella, in 2007 vaccine recommendations were revised and a routine two-dose schedule was implemented. The impact of varicella disease pre- and post-vaccine licensure is illustrated in Figure 2. Not listed, is that in the pre-vaccine era, there were approximately 44 cases of congenital varicella syndrome annually.
As of 2023 only 23% (45/195) of nations routinely administer this vaccine and 4% (8/195) have restricted recommendations. The remaining 73% of countries do not offer the vaccine, including all countries on the African continent, and Cuba, Guatemala, Haiti, Honduras, India, Jordan, Lebanon, Philippines, Portugal, and Venezuela to list a few.
Varicella Outbreak: In October 2022, New York City (NYC) identified a varicella outbreak primarily involving persons who recently migrated from Central and South America and lived in a shelter in NYC or residential facility (n = 105); the outbreak is ongoing. As of March 8, 2024, 873 cases (53%) were among children aged 4-18 years and 91.9% had no documentation of varicella vaccine at time of symptom onset. There were 28 hospitalizations, and no deaths reported. The most common sources of transmission were the residential facilities (41.3%) and importation or possible importation (39.4%). School transmission accounted for only 1.2% of cases.
Most migrants arrived from countries where varicella vaccination is not part of the routine childhood immunization schedule. Although most cases occurred in children, almost 30% occurred in adults. Many of the migrants arrived from tropical countries where susceptibility rates are also higher in adults. This outbreak is a reminder of the importance of limiting disease transmission by maintaining high vaccination rates. To curtail this outbreak, approximately 27,000 doses of varicella vaccine were administered to the arriving migrants. In addition, MMR, COVID-19, influenza, and all routine pediatric vaccines required for school entry were administered. Temporary closure of the residential facilities were required. Education was provided to residents regarding immunizations as well as assistance to help them establish a primary care home. Multiple agencies were mobilized to successfully coordinate these efforts.
Take Home Message
1. Each country has its own routine immunization schedule. It may not include all vaccines recommended in the US schedule. When questioned I’m frequently told that immunizations are up to date, only to review records and find they are not, especially when it is related to MMR. It is often administered at 9 months and/or MR or MM is administered depending on the country. As reported here, varicella is a routine vaccine in only 45 countries.
2.
3. Once an outbreak has been identified, the infrastructure to manage and contain it must already be established. In most instances there will be a need for a rapid and often large-scale effort involving multiple agencies including local health care providers.
4. Not all diseases are reportable. Only deaths by varicella are nationally notifiable. Otherwise, cases are reported voluntarily. As of November 2, 2024, there have been 5,157 cases of varicella reported, excluding any cases from NYC.
Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
Suggested Reading
CDC. Nationally Notifiable Infectious Diseases and Conditions, United States: Weekly Tables. https://wonder.cdc.gov/nndss/nndss_weekly_tables_menu.asp.
Graham KA et al. Varicella Outbreak Among Recent Arrivals to New York City, 2022-2024. MMWR Morb Mortal Wkly Rep. 2024 May 30;73(21):478-483. doi: 10.15585/mmwr.mm7321a1.
Marin M et al. Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020. J Infect Dis. 2022 Oct 21;226(Suppl 4):S463-S469. doi: 10.1093/infdis/jiac271.
Varicella-Zoster Virus Infections in Kimberkin DW et al, eds. Red Book: 2024 Report of the Committee on Infectious Diseases, 33rd Edition. American Academy of Pediatrics, 2024:938-951. https://www.aap.org/Red-Book-2024-Report-of-the-Committee-on-Infectious-Diseases-33rd-Edition-Paperback?srsltid=AfmBOoqyF60rR9ZwQ5jA8AouNhtRRTyPLnc_r7HWw7JVYV8v33Hr2vQS.
‘Being a Doctor Isn’t Healthy’: Train Your Body to Handle It
Heather K. Schopper, MD, a head and neck surgeon at Penn State Health, Hershey, Pennsylvania, wasn’t long into her career when she began feeling its physical demands. Standing for 12 hours at a time, holding awkward positions for long periods, and working with surgical tables and instruments made for doctors much taller and larger meant severe back, shoulder, and neck pain at the end of every shift.
“You just want to lie down on the floor at the end of the day,” Schopper explained. “The wear and tear of our profession is really challenging.”
Here’s the thing: At the time Schopper wasn’t particularly out of shape. She only knew she needed to build up her body for long days and a long career. What, physically, would that look like?
This was the catalyst for what she calls a “health and fitness journey” that transformed the way she practices.
“Medicine is unique in its physical demands,” said Meghan Wieser, PT, DPT, a doctor of physical therapy at Recharge Health and Fitness in Ellicott City, Maryland. Wieser frequently works with physicians and others in high-stress career environments, and she’s observed the serious toll that physically demanding medical practice can take on the body.
It’s not just about preventing acute or chronic injury, she said. It’s about performing better for longer periods. And every doctor knows the only way to build a more functional body is training.
The Fantasy of Physical Perfection vs the Reality of, Well, Reality
Jordan D. Metzl, MD, is a sports medicine physician at Hospital for Special Surgery (HSS) in New York City. He’s also a lifelong triathlete and marathon runner and has parlayed that passion into an online fitness community of more than 10,000 people called Ironstrength. Through that, Metzl has led free exercise classes in Central Park for years. He doesn’t dabble. Three times a year he leads a boot camp class of more than 1000 people on the flight deck of the USS Intrepid on the Hudson River.
“I get it, being a doctor is all about the hours,” he said. “The time sacrifices get brutal and you have to cut something out, sometimes every day. For a lot of us, that’s exercise.”
Metzl understands it so well that he recently began leading twice-monthly boot camp classes just for his HSS physician colleagues on Wednesday mornings. He says those doctors both want and need that extra boost and will be aggressive about making time for it.
“The better shape you’re in, the better job you’ll do as a physician,” he said. “You’ll feel better when the hours get long. In my own career, I have always been a better doctor when I’m active and in shape.”
Knowledge isn’t really the issue for physicians. Reality is. And reality dictates that doctors have just as much issue with achieving consistency as any patient they prescribe exercise to.
Metzl suggests total body functional training to mimic real-world movement, particularly core and lower body to keep you upright for hours at a time. How do you schedule that? He uses early mornings and weekends to train for his races and run his fitness classes, which is why his primary advice is to focus not on the activity, but on time.
“Schedule full workouts when you can and steal the rest,” he said.
Schopper agrees. “You may not be able to fit in 60 minutes of exercise every day, but 20-30 minutes of intentional movement is key,” she explained. “When you have a day off, prioritize a longer session of something you can’t fit in on workdays.”
Those shorter bouts of exercise might include “bookending” the day with 10 minutes of burpees in the morning and then 10 minutes of bodyweight strength moves like planks, push-ups, and air squats in the evening.
“Bodyweight exercises are low-hanging fruit,” said Wieser. “If you’ve got a short window, aim for something that can shoot your heart rate up quickly.”
You can also throw in “movement snacks” throughout the day — skip the elevator and run up a flight of stairs, walk around during a quick lunch break, or throw in a set of jumping jacks between patients. (Don’t worry — you won’t be dripping sweat when they walk in.)
Remember, the rehab room in the orthopedic wing may have a few dumbbells and exercise bands you can utilize when you have 5 extra minutes in your day. “Any way you can squeeze in extra movement counts,” said Wieser.
Feats of Strength? Neighborhood Sprints? It All Matters
Kissinger Goldman, DO, a Florida-based ER physician, began his dedication to exercise 17 years ago, after a high-cholesterol diagnosis. “Did I have time to exercise in medical school and residency? Yes,” Goldman admitted. “But I didn’t have the same commitment to my health until I received that number. I set about to change everything.”
Goldman follows the approach of dividing up his exercise routine into short or long sessions, depending on his schedule. “If I’m off, I’ll aim for 30 minutes of cardio and 30 minutes of strength and core work,” he explained. “When I have to work, I’ll do a compressed version of that routine as soon as I wake up, and make sure the cardio is very intense — I’ll sprint in my neighborhood, for instance.”
Matt Klein, a doctor of physical therapy and professor at George Fox University in Newberg, Oregon, who has treated many doctors, says that, when pushed for time, just 20 minutes of “heavy” strength training can deliver good results. “The definition of heavy will vary, but aim for a weight that is challenging, whether a beginner or a more experienced exerciser,” he said. “Most doctors won’t have time to go to the gym, so a simple set of dumbbells or kettlebells will work just fine. The easier it is to access, the more likely you are to do it consistently.”
Klein is a fan of strength training with good reason: “Strength is a predictor of chronic disease, so doing some high-level strength training or power training can go a long way,” he said.
The endorphin high and overall sense of improved well-being are an extra bonus. Goldman credits it with ensuring he rarely misses a workout.
Get Hardcore About Sleep
Consider the following passage: “There are clear negative effects of sleep deprivation on performance, including reaction time, accuracy, vigor, submaximal strength, and endurance. Cognitive functions such as judgment and decision-making also suffer.”
Does that sound like how you feel on suboptimal sleep? That’s from an International Journal of Sports Medicine study on the effects of sleep deprivation on athletes.
Athletes aren’t doctors — but when you consider “reaction time, accuracy, endurance, judgment, and decision-making” — doctors could certainly benefit by thinking like athletes.
Schopper is serious about sleep and sets firm boundaries.
“It’s hard,” she admitted. “We want to work, see our families, have fun. But I work hard to say, ‘I’m done,’ and go to bed.”
“Rest is crucial for this job,” agreed Goldman. “If you don’t have adequate sleep, your cortisone levels are going to go up. When you’re exhausted and you’re working, you’re likely to miss something.” Goldman is consistent with early bedtimes around 9:00 or 9:30 PM, and he allows for a bit of “wind-down” time by reading for about 20 minutes before nodding off.
Goldman also sees a link between rest and improved interactions with patients. “There’s a direct correlation between number of hours worked in a row with respect to ‘customer service’ with patients,” he said.
But don’t aim for perfection. Allow some wiggle room for the time you spend asleep, Klein recommends. “We’ve always aimed for 8 hours, but there’s evidence that even 6 or 7 hours can be enough to allow you to recover as needed,” he said. “Optimally, you want that to be uninterrupted, but if not, a 10-minute power nap can help with mental clarity.”
Keep Searching, Keep Trying, Keep Training
Schopper was never, nor has she become, a gym rat. Still, “I knew I needed to build upper body strength,” she said. That meant expanding her fitness possibilities beyond the obvious. She discovered aerial arts — intense workouts using straps and other suspension tools to work every muscle in her body while hanging from the ceiling. Increased strength was a given, but she also seriously increased her range of motion.
For Schopper, the improvements to her lifestyle have been game changers. “I still have long days, but I’m no longer sore and tired after them,” she said. “I sleep better and have more energy. I’m proud of myself for putting the effort into this.”
A journey toward health and fitness may look different for everyone, but (as doctors frequently tell their patients) it’s a path anyone can follow.
“Being a doctor is not necessarily good for your health,” said Klein. “The body can handle the job, however, if you train for it.”
A version of this article first appeared on Medscape.com.
Heather K. Schopper, MD, a head and neck surgeon at Penn State Health, Hershey, Pennsylvania, wasn’t long into her career when she began feeling its physical demands. Standing for 12 hours at a time, holding awkward positions for long periods, and working with surgical tables and instruments made for doctors much taller and larger meant severe back, shoulder, and neck pain at the end of every shift.
“You just want to lie down on the floor at the end of the day,” Schopper explained. “The wear and tear of our profession is really challenging.”
Here’s the thing: At the time Schopper wasn’t particularly out of shape. She only knew she needed to build up her body for long days and a long career. What, physically, would that look like?
This was the catalyst for what she calls a “health and fitness journey” that transformed the way she practices.
“Medicine is unique in its physical demands,” said Meghan Wieser, PT, DPT, a doctor of physical therapy at Recharge Health and Fitness in Ellicott City, Maryland. Wieser frequently works with physicians and others in high-stress career environments, and she’s observed the serious toll that physically demanding medical practice can take on the body.
It’s not just about preventing acute or chronic injury, she said. It’s about performing better for longer periods. And every doctor knows the only way to build a more functional body is training.
The Fantasy of Physical Perfection vs the Reality of, Well, Reality
Jordan D. Metzl, MD, is a sports medicine physician at Hospital for Special Surgery (HSS) in New York City. He’s also a lifelong triathlete and marathon runner and has parlayed that passion into an online fitness community of more than 10,000 people called Ironstrength. Through that, Metzl has led free exercise classes in Central Park for years. He doesn’t dabble. Three times a year he leads a boot camp class of more than 1000 people on the flight deck of the USS Intrepid on the Hudson River.
“I get it, being a doctor is all about the hours,” he said. “The time sacrifices get brutal and you have to cut something out, sometimes every day. For a lot of us, that’s exercise.”
Metzl understands it so well that he recently began leading twice-monthly boot camp classes just for his HSS physician colleagues on Wednesday mornings. He says those doctors both want and need that extra boost and will be aggressive about making time for it.
“The better shape you’re in, the better job you’ll do as a physician,” he said. “You’ll feel better when the hours get long. In my own career, I have always been a better doctor when I’m active and in shape.”
Knowledge isn’t really the issue for physicians. Reality is. And reality dictates that doctors have just as much issue with achieving consistency as any patient they prescribe exercise to.
Metzl suggests total body functional training to mimic real-world movement, particularly core and lower body to keep you upright for hours at a time. How do you schedule that? He uses early mornings and weekends to train for his races and run his fitness classes, which is why his primary advice is to focus not on the activity, but on time.
“Schedule full workouts when you can and steal the rest,” he said.
Schopper agrees. “You may not be able to fit in 60 minutes of exercise every day, but 20-30 minutes of intentional movement is key,” she explained. “When you have a day off, prioritize a longer session of something you can’t fit in on workdays.”
Those shorter bouts of exercise might include “bookending” the day with 10 minutes of burpees in the morning and then 10 minutes of bodyweight strength moves like planks, push-ups, and air squats in the evening.
“Bodyweight exercises are low-hanging fruit,” said Wieser. “If you’ve got a short window, aim for something that can shoot your heart rate up quickly.”
You can also throw in “movement snacks” throughout the day — skip the elevator and run up a flight of stairs, walk around during a quick lunch break, or throw in a set of jumping jacks between patients. (Don’t worry — you won’t be dripping sweat when they walk in.)
Remember, the rehab room in the orthopedic wing may have a few dumbbells and exercise bands you can utilize when you have 5 extra minutes in your day. “Any way you can squeeze in extra movement counts,” said Wieser.
Feats of Strength? Neighborhood Sprints? It All Matters
Kissinger Goldman, DO, a Florida-based ER physician, began his dedication to exercise 17 years ago, after a high-cholesterol diagnosis. “Did I have time to exercise in medical school and residency? Yes,” Goldman admitted. “But I didn’t have the same commitment to my health until I received that number. I set about to change everything.”
Goldman follows the approach of dividing up his exercise routine into short or long sessions, depending on his schedule. “If I’m off, I’ll aim for 30 minutes of cardio and 30 minutes of strength and core work,” he explained. “When I have to work, I’ll do a compressed version of that routine as soon as I wake up, and make sure the cardio is very intense — I’ll sprint in my neighborhood, for instance.”
Matt Klein, a doctor of physical therapy and professor at George Fox University in Newberg, Oregon, who has treated many doctors, says that, when pushed for time, just 20 minutes of “heavy” strength training can deliver good results. “The definition of heavy will vary, but aim for a weight that is challenging, whether a beginner or a more experienced exerciser,” he said. “Most doctors won’t have time to go to the gym, so a simple set of dumbbells or kettlebells will work just fine. The easier it is to access, the more likely you are to do it consistently.”
Klein is a fan of strength training with good reason: “Strength is a predictor of chronic disease, so doing some high-level strength training or power training can go a long way,” he said.
The endorphin high and overall sense of improved well-being are an extra bonus. Goldman credits it with ensuring he rarely misses a workout.
Get Hardcore About Sleep
Consider the following passage: “There are clear negative effects of sleep deprivation on performance, including reaction time, accuracy, vigor, submaximal strength, and endurance. Cognitive functions such as judgment and decision-making also suffer.”
Does that sound like how you feel on suboptimal sleep? That’s from an International Journal of Sports Medicine study on the effects of sleep deprivation on athletes.
Athletes aren’t doctors — but when you consider “reaction time, accuracy, endurance, judgment, and decision-making” — doctors could certainly benefit by thinking like athletes.
Schopper is serious about sleep and sets firm boundaries.
“It’s hard,” she admitted. “We want to work, see our families, have fun. But I work hard to say, ‘I’m done,’ and go to bed.”
“Rest is crucial for this job,” agreed Goldman. “If you don’t have adequate sleep, your cortisone levels are going to go up. When you’re exhausted and you’re working, you’re likely to miss something.” Goldman is consistent with early bedtimes around 9:00 or 9:30 PM, and he allows for a bit of “wind-down” time by reading for about 20 minutes before nodding off.
Goldman also sees a link between rest and improved interactions with patients. “There’s a direct correlation between number of hours worked in a row with respect to ‘customer service’ with patients,” he said.
But don’t aim for perfection. Allow some wiggle room for the time you spend asleep, Klein recommends. “We’ve always aimed for 8 hours, but there’s evidence that even 6 or 7 hours can be enough to allow you to recover as needed,” he said. “Optimally, you want that to be uninterrupted, but if not, a 10-minute power nap can help with mental clarity.”
Keep Searching, Keep Trying, Keep Training
Schopper was never, nor has she become, a gym rat. Still, “I knew I needed to build upper body strength,” she said. That meant expanding her fitness possibilities beyond the obvious. She discovered aerial arts — intense workouts using straps and other suspension tools to work every muscle in her body while hanging from the ceiling. Increased strength was a given, but she also seriously increased her range of motion.
For Schopper, the improvements to her lifestyle have been game changers. “I still have long days, but I’m no longer sore and tired after them,” she said. “I sleep better and have more energy. I’m proud of myself for putting the effort into this.”
A journey toward health and fitness may look different for everyone, but (as doctors frequently tell their patients) it’s a path anyone can follow.
“Being a doctor is not necessarily good for your health,” said Klein. “The body can handle the job, however, if you train for it.”
A version of this article first appeared on Medscape.com.
Heather K. Schopper, MD, a head and neck surgeon at Penn State Health, Hershey, Pennsylvania, wasn’t long into her career when she began feeling its physical demands. Standing for 12 hours at a time, holding awkward positions for long periods, and working with surgical tables and instruments made for doctors much taller and larger meant severe back, shoulder, and neck pain at the end of every shift.
“You just want to lie down on the floor at the end of the day,” Schopper explained. “The wear and tear of our profession is really challenging.”
Here’s the thing: At the time Schopper wasn’t particularly out of shape. She only knew she needed to build up her body for long days and a long career. What, physically, would that look like?
This was the catalyst for what she calls a “health and fitness journey” that transformed the way she practices.
“Medicine is unique in its physical demands,” said Meghan Wieser, PT, DPT, a doctor of physical therapy at Recharge Health and Fitness in Ellicott City, Maryland. Wieser frequently works with physicians and others in high-stress career environments, and she’s observed the serious toll that physically demanding medical practice can take on the body.
It’s not just about preventing acute or chronic injury, she said. It’s about performing better for longer periods. And every doctor knows the only way to build a more functional body is training.
The Fantasy of Physical Perfection vs the Reality of, Well, Reality
Jordan D. Metzl, MD, is a sports medicine physician at Hospital for Special Surgery (HSS) in New York City. He’s also a lifelong triathlete and marathon runner and has parlayed that passion into an online fitness community of more than 10,000 people called Ironstrength. Through that, Metzl has led free exercise classes in Central Park for years. He doesn’t dabble. Three times a year he leads a boot camp class of more than 1000 people on the flight deck of the USS Intrepid on the Hudson River.
“I get it, being a doctor is all about the hours,” he said. “The time sacrifices get brutal and you have to cut something out, sometimes every day. For a lot of us, that’s exercise.”
Metzl understands it so well that he recently began leading twice-monthly boot camp classes just for his HSS physician colleagues on Wednesday mornings. He says those doctors both want and need that extra boost and will be aggressive about making time for it.
“The better shape you’re in, the better job you’ll do as a physician,” he said. “You’ll feel better when the hours get long. In my own career, I have always been a better doctor when I’m active and in shape.”
Knowledge isn’t really the issue for physicians. Reality is. And reality dictates that doctors have just as much issue with achieving consistency as any patient they prescribe exercise to.
Metzl suggests total body functional training to mimic real-world movement, particularly core and lower body to keep you upright for hours at a time. How do you schedule that? He uses early mornings and weekends to train for his races and run his fitness classes, which is why his primary advice is to focus not on the activity, but on time.
“Schedule full workouts when you can and steal the rest,” he said.
Schopper agrees. “You may not be able to fit in 60 minutes of exercise every day, but 20-30 minutes of intentional movement is key,” she explained. “When you have a day off, prioritize a longer session of something you can’t fit in on workdays.”
Those shorter bouts of exercise might include “bookending” the day with 10 minutes of burpees in the morning and then 10 minutes of bodyweight strength moves like planks, push-ups, and air squats in the evening.
“Bodyweight exercises are low-hanging fruit,” said Wieser. “If you’ve got a short window, aim for something that can shoot your heart rate up quickly.”
You can also throw in “movement snacks” throughout the day — skip the elevator and run up a flight of stairs, walk around during a quick lunch break, or throw in a set of jumping jacks between patients. (Don’t worry — you won’t be dripping sweat when they walk in.)
Remember, the rehab room in the orthopedic wing may have a few dumbbells and exercise bands you can utilize when you have 5 extra minutes in your day. “Any way you can squeeze in extra movement counts,” said Wieser.
Feats of Strength? Neighborhood Sprints? It All Matters
Kissinger Goldman, DO, a Florida-based ER physician, began his dedication to exercise 17 years ago, after a high-cholesterol diagnosis. “Did I have time to exercise in medical school and residency? Yes,” Goldman admitted. “But I didn’t have the same commitment to my health until I received that number. I set about to change everything.”
Goldman follows the approach of dividing up his exercise routine into short or long sessions, depending on his schedule. “If I’m off, I’ll aim for 30 minutes of cardio and 30 minutes of strength and core work,” he explained. “When I have to work, I’ll do a compressed version of that routine as soon as I wake up, and make sure the cardio is very intense — I’ll sprint in my neighborhood, for instance.”
Matt Klein, a doctor of physical therapy and professor at George Fox University in Newberg, Oregon, who has treated many doctors, says that, when pushed for time, just 20 minutes of “heavy” strength training can deliver good results. “The definition of heavy will vary, but aim for a weight that is challenging, whether a beginner or a more experienced exerciser,” he said. “Most doctors won’t have time to go to the gym, so a simple set of dumbbells or kettlebells will work just fine. The easier it is to access, the more likely you are to do it consistently.”
Klein is a fan of strength training with good reason: “Strength is a predictor of chronic disease, so doing some high-level strength training or power training can go a long way,” he said.
The endorphin high and overall sense of improved well-being are an extra bonus. Goldman credits it with ensuring he rarely misses a workout.
Get Hardcore About Sleep
Consider the following passage: “There are clear negative effects of sleep deprivation on performance, including reaction time, accuracy, vigor, submaximal strength, and endurance. Cognitive functions such as judgment and decision-making also suffer.”
Does that sound like how you feel on suboptimal sleep? That’s from an International Journal of Sports Medicine study on the effects of sleep deprivation on athletes.
Athletes aren’t doctors — but when you consider “reaction time, accuracy, endurance, judgment, and decision-making” — doctors could certainly benefit by thinking like athletes.
Schopper is serious about sleep and sets firm boundaries.
“It’s hard,” she admitted. “We want to work, see our families, have fun. But I work hard to say, ‘I’m done,’ and go to bed.”
“Rest is crucial for this job,” agreed Goldman. “If you don’t have adequate sleep, your cortisone levels are going to go up. When you’re exhausted and you’re working, you’re likely to miss something.” Goldman is consistent with early bedtimes around 9:00 or 9:30 PM, and he allows for a bit of “wind-down” time by reading for about 20 minutes before nodding off.
Goldman also sees a link between rest and improved interactions with patients. “There’s a direct correlation between number of hours worked in a row with respect to ‘customer service’ with patients,” he said.
But don’t aim for perfection. Allow some wiggle room for the time you spend asleep, Klein recommends. “We’ve always aimed for 8 hours, but there’s evidence that even 6 or 7 hours can be enough to allow you to recover as needed,” he said. “Optimally, you want that to be uninterrupted, but if not, a 10-minute power nap can help with mental clarity.”
Keep Searching, Keep Trying, Keep Training
Schopper was never, nor has she become, a gym rat. Still, “I knew I needed to build upper body strength,” she said. That meant expanding her fitness possibilities beyond the obvious. She discovered aerial arts — intense workouts using straps and other suspension tools to work every muscle in her body while hanging from the ceiling. Increased strength was a given, but she also seriously increased her range of motion.
For Schopper, the improvements to her lifestyle have been game changers. “I still have long days, but I’m no longer sore and tired after them,” she said. “I sleep better and have more energy. I’m proud of myself for putting the effort into this.”
A journey toward health and fitness may look different for everyone, but (as doctors frequently tell their patients) it’s a path anyone can follow.
“Being a doctor is not necessarily good for your health,” said Klein. “The body can handle the job, however, if you train for it.”
A version of this article first appeared on Medscape.com.
CRC Screening Uptake Rises in Adults Aged 45-49 Years
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Diet Matters in Prostate Cancer, but It’s Complicated
Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.
In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.
These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.
“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”
What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”
Oncologist and Nutritionist Collaborate on Multiple Studies
Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.
Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.
Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).
In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.
Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.
The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.
Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.
Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”
More Than One Approach Likely to Work
Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.
“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”
Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.
Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)
Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.
On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.
Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.
But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.
“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.
Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.
“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”
Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.
A version of this article first appeared on Medscape.com.
Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.
In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.
These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.
“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”
What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”
Oncologist and Nutritionist Collaborate on Multiple Studies
Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.
Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.
Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).
In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.
Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.
The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.
Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.
Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”
More Than One Approach Likely to Work
Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.
“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”
Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.
Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)
Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.
On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.
Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.
But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.
“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.
Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.
“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”
Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.
A version of this article first appeared on Medscape.com.
Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.
In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.
These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.
“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”
What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”
Oncologist and Nutritionist Collaborate on Multiple Studies
Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.
Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.
Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).
In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.
Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.
The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.
Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.
Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”
More Than One Approach Likely to Work
Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.
“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”
Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.
Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)
Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.
On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.
Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.
But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.
“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.
Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.
“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”
Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.
A version of this article first appeared on Medscape.com.
PET/CT Imaging Study Reveals Differing Views on How to Manage Incidental Findings
Disparate views on managing incidental imaging findings made during clinical research — particularly for unclear results — signal a need for standardized guidance, according to recent survey results.
Respondents were split on whether it was the site primary investigator’s responsibility to decide which incidental findings should be reported back to the patient, and the most commonly cited challenges included adequately explaining these findings and the follow-up required. These issues were most present when dealing with nonspecific incidental findings or findings of unclear importance, said lead author Jane S. Kang, MD, a bioethicist and associate professor of medicine in the Division of Rheumatology at Columbia University Irving Medical Center, New York City.
“It can be difficult to have a clear approach” when it comes to these situations that are not black and white, and it is hard to get a clear answer, she said in an interview.
The survey included responses from investigators from the Treatments Against Rheumatoid Arthritis and Effect on 18F-fluorodeoxyglucose (FDG) PET/CT (TARGET) trial, conducted between 2015 and 2021. The 24-week trial included patients from 28 centers in the United States to investigate how different disease-modifying antirheumatic drugs can reduce cardiovascular and joint inflammation, assessed via whole body FDG PET/CT. The survey was a planned substudy of the TARGET trial and is “the first study that examines researchers’ attitudes and beliefs regarding incidental research findings from whole body FDG PET/CT,” Kang and her coauthors wrote.
This news organization reported the main results of the TARGET trial in 2022.
Eighteen of the 28 site primary investigators (PIs) of the TARGET trial participated in the survey, which was published in Arthritis Care & Research in September 2024.
TARGET Trial Incidental Findings
The TARGET trial enrolled 159 patients, of whom 82% had at least one incidental finding and 62% had one or more FDG-avid incidental findings. There were 46 “clinically actionable findings” for 40 participants overall; the reading radiologists recommended additional imaging for 28 findings and specialist consultation or procedural evaluation for 15 findings.
Details on these incidental findings were presented in a poster at the annual meeting of the American College of Rheumatology (ACR), held in Washington, DC.
The most common non–FDG-avid findings were pulmonary nodules, diverticulosis, cholelithiasis, sinus disease, and vascular calcifications. The most common FDG-avid findings were hypermetabolic lymphadenopathy, increased gastric/esophageal uptake, increased bowel uptake, and increased pharyngeal uptake.
In the related survey, 11 respondents (61%) said they returned any incidental findings to participants and 5 (28%) did not; the remaining 2 respondents did not know.
Across all study PIs, 22% felt that incidental findings were beneficial, 39% said they were potentially beneficial, and 11% said they were potentially detrimental. PIs that ranked incidental findings as potentially detrimental pointed to how these findings led to invasive additional testing.
“One of my subjects was found to have diverticulosis, which needed an invasive procedure to rule out malignancy,” one respondent wrote. “However, the subject had already had a colonoscopy months prior to the PET findings, which was still not deemed sufficient by the nuclear radiologist and GI consultant, so he had to have another colonoscopy, which was benign, but uncomfortable.”
Obligation to Return Findings
All investigators agreed that incidental findings should be shared with patients if they revealed a high-risk medical condition that can be treated; had important health implications such as premature death or substantial morbidity; and their health could be improved with proven preventive or therapeutic interventions.
There was more disagreement on whether to share that the FDG PET/CT revealed no findings or if the test revealed a finding without clear medical importance of which the research participant may not be aware.
An example of a less-specific finding could be something like increased FDG uptake in a particular area, like the bowel, Kang explained.
“The question is: What does that mean?” she said. “How do you interpret that?”
While some PIs might feel obligated to share all results with patients, sharing ambiguous incidental findings will likely not be helpful to the patient, said Arthur Caplan, PhD, of the Division of Medical Ethics at New York University (NYU) Grossman School of Medicine, New York City.
“Dealing in unknowns and uncertainties when you’re diagnosing doesn’t really do people very much good,” he said in an interview.
While most survey respondents said they were at least moderately obligated to disclose incidental research findings if a patient requests them, Caplan noted that it was ultimately the researchers’ decision.
“Patient preferences are something to take into account, but they’re not final. If the research team says, ‘we don’t know, it’s too uncertain, it’s too new,’ then I don’t think they have any obligation to return that [information],” he said. “You can’t tell somebody what you don’t understand.”
Conversely, the clearer the incidental finding, the stronger the obligation to share that information with research participants, he continued.
Need for a Standardized Approach
The TARGET study, like many research studies, left the management of incidental imaging findings to individual research sites and investigators.
It’s possible that different sites responded to these ambiguous clinical findings in different ways, Kang noted.
“If there’s a situation that’s difficult to interpret as it is, you can imagine that the resulting actions that may result from that can vary, too,” she said, which highlights the need for more specific and standardized guidance.
One way to approach this, Caplan noted, is establishing an agreed-upon approach for dealing with any incidental findings across all research sites before a study begins.
“If there is going to be a common study at many sites, then they should have a common response on what they are going to do,” he noted, and how they will share that information effectively with the research participants to ensure it’s understandable. However, in a lot of research studies, each site has its own approach.
“Right now, it’s all over the place and that shouldn’t be,” he said.
Institutional review boards (IRBs) could be one resource to help build detailed guidance on managing unclear incidental findings in future research, wrote Kang and coauthors.
“For incidental findings from whole body FDG PET/CT that are not clearly actionable or less straightforward, IRBs may consider requiring a certain level of follow-up for different categories or types of incidental findings or require that all incidental findings are reviewed by an independent group that would provide timely recommendations on the most appropriate return and management of those findings,” Kang and colleagues wrote. “With IRB guidance, very specific and detailed policies and procedures for returning and managing incidental findings should be established for every study, with consistency among the research sites of multicenter trials.”
The TARGET trial and survey were funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Kang reported receiving research funding from the National Institutes of Health and the Rheumatology Research Foundation. Caplan serves as a contributing author for this news organization and served on an independent bioethics panel for compassionate drug use that was funded by Johnson & Johnson through the NYU Grossman School of Medicine.
A version of this article first appeared on Medscape.com.
Disparate views on managing incidental imaging findings made during clinical research — particularly for unclear results — signal a need for standardized guidance, according to recent survey results.
Respondents were split on whether it was the site primary investigator’s responsibility to decide which incidental findings should be reported back to the patient, and the most commonly cited challenges included adequately explaining these findings and the follow-up required. These issues were most present when dealing with nonspecific incidental findings or findings of unclear importance, said lead author Jane S. Kang, MD, a bioethicist and associate professor of medicine in the Division of Rheumatology at Columbia University Irving Medical Center, New York City.
“It can be difficult to have a clear approach” when it comes to these situations that are not black and white, and it is hard to get a clear answer, she said in an interview.
The survey included responses from investigators from the Treatments Against Rheumatoid Arthritis and Effect on 18F-fluorodeoxyglucose (FDG) PET/CT (TARGET) trial, conducted between 2015 and 2021. The 24-week trial included patients from 28 centers in the United States to investigate how different disease-modifying antirheumatic drugs can reduce cardiovascular and joint inflammation, assessed via whole body FDG PET/CT. The survey was a planned substudy of the TARGET trial and is “the first study that examines researchers’ attitudes and beliefs regarding incidental research findings from whole body FDG PET/CT,” Kang and her coauthors wrote.
This news organization reported the main results of the TARGET trial in 2022.
Eighteen of the 28 site primary investigators (PIs) of the TARGET trial participated in the survey, which was published in Arthritis Care & Research in September 2024.
TARGET Trial Incidental Findings
The TARGET trial enrolled 159 patients, of whom 82% had at least one incidental finding and 62% had one or more FDG-avid incidental findings. There were 46 “clinically actionable findings” for 40 participants overall; the reading radiologists recommended additional imaging for 28 findings and specialist consultation or procedural evaluation for 15 findings.
Details on these incidental findings were presented in a poster at the annual meeting of the American College of Rheumatology (ACR), held in Washington, DC.
The most common non–FDG-avid findings were pulmonary nodules, diverticulosis, cholelithiasis, sinus disease, and vascular calcifications. The most common FDG-avid findings were hypermetabolic lymphadenopathy, increased gastric/esophageal uptake, increased bowel uptake, and increased pharyngeal uptake.
In the related survey, 11 respondents (61%) said they returned any incidental findings to participants and 5 (28%) did not; the remaining 2 respondents did not know.
Across all study PIs, 22% felt that incidental findings were beneficial, 39% said they were potentially beneficial, and 11% said they were potentially detrimental. PIs that ranked incidental findings as potentially detrimental pointed to how these findings led to invasive additional testing.
“One of my subjects was found to have diverticulosis, which needed an invasive procedure to rule out malignancy,” one respondent wrote. “However, the subject had already had a colonoscopy months prior to the PET findings, which was still not deemed sufficient by the nuclear radiologist and GI consultant, so he had to have another colonoscopy, which was benign, but uncomfortable.”
Obligation to Return Findings
All investigators agreed that incidental findings should be shared with patients if they revealed a high-risk medical condition that can be treated; had important health implications such as premature death or substantial morbidity; and their health could be improved with proven preventive or therapeutic interventions.
There was more disagreement on whether to share that the FDG PET/CT revealed no findings or if the test revealed a finding without clear medical importance of which the research participant may not be aware.
An example of a less-specific finding could be something like increased FDG uptake in a particular area, like the bowel, Kang explained.
“The question is: What does that mean?” she said. “How do you interpret that?”
While some PIs might feel obligated to share all results with patients, sharing ambiguous incidental findings will likely not be helpful to the patient, said Arthur Caplan, PhD, of the Division of Medical Ethics at New York University (NYU) Grossman School of Medicine, New York City.
“Dealing in unknowns and uncertainties when you’re diagnosing doesn’t really do people very much good,” he said in an interview.
While most survey respondents said they were at least moderately obligated to disclose incidental research findings if a patient requests them, Caplan noted that it was ultimately the researchers’ decision.
“Patient preferences are something to take into account, but they’re not final. If the research team says, ‘we don’t know, it’s too uncertain, it’s too new,’ then I don’t think they have any obligation to return that [information],” he said. “You can’t tell somebody what you don’t understand.”
Conversely, the clearer the incidental finding, the stronger the obligation to share that information with research participants, he continued.
Need for a Standardized Approach
The TARGET study, like many research studies, left the management of incidental imaging findings to individual research sites and investigators.
It’s possible that different sites responded to these ambiguous clinical findings in different ways, Kang noted.
“If there’s a situation that’s difficult to interpret as it is, you can imagine that the resulting actions that may result from that can vary, too,” she said, which highlights the need for more specific and standardized guidance.
One way to approach this, Caplan noted, is establishing an agreed-upon approach for dealing with any incidental findings across all research sites before a study begins.
“If there is going to be a common study at many sites, then they should have a common response on what they are going to do,” he noted, and how they will share that information effectively with the research participants to ensure it’s understandable. However, in a lot of research studies, each site has its own approach.
“Right now, it’s all over the place and that shouldn’t be,” he said.
Institutional review boards (IRBs) could be one resource to help build detailed guidance on managing unclear incidental findings in future research, wrote Kang and coauthors.
“For incidental findings from whole body FDG PET/CT that are not clearly actionable or less straightforward, IRBs may consider requiring a certain level of follow-up for different categories or types of incidental findings or require that all incidental findings are reviewed by an independent group that would provide timely recommendations on the most appropriate return and management of those findings,” Kang and colleagues wrote. “With IRB guidance, very specific and detailed policies and procedures for returning and managing incidental findings should be established for every study, with consistency among the research sites of multicenter trials.”
The TARGET trial and survey were funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Kang reported receiving research funding from the National Institutes of Health and the Rheumatology Research Foundation. Caplan serves as a contributing author for this news organization and served on an independent bioethics panel for compassionate drug use that was funded by Johnson & Johnson through the NYU Grossman School of Medicine.
A version of this article first appeared on Medscape.com.
Disparate views on managing incidental imaging findings made during clinical research — particularly for unclear results — signal a need for standardized guidance, according to recent survey results.
Respondents were split on whether it was the site primary investigator’s responsibility to decide which incidental findings should be reported back to the patient, and the most commonly cited challenges included adequately explaining these findings and the follow-up required. These issues were most present when dealing with nonspecific incidental findings or findings of unclear importance, said lead author Jane S. Kang, MD, a bioethicist and associate professor of medicine in the Division of Rheumatology at Columbia University Irving Medical Center, New York City.
“It can be difficult to have a clear approach” when it comes to these situations that are not black and white, and it is hard to get a clear answer, she said in an interview.
The survey included responses from investigators from the Treatments Against Rheumatoid Arthritis and Effect on 18F-fluorodeoxyglucose (FDG) PET/CT (TARGET) trial, conducted between 2015 and 2021. The 24-week trial included patients from 28 centers in the United States to investigate how different disease-modifying antirheumatic drugs can reduce cardiovascular and joint inflammation, assessed via whole body FDG PET/CT. The survey was a planned substudy of the TARGET trial and is “the first study that examines researchers’ attitudes and beliefs regarding incidental research findings from whole body FDG PET/CT,” Kang and her coauthors wrote.
This news organization reported the main results of the TARGET trial in 2022.
Eighteen of the 28 site primary investigators (PIs) of the TARGET trial participated in the survey, which was published in Arthritis Care & Research in September 2024.
TARGET Trial Incidental Findings
The TARGET trial enrolled 159 patients, of whom 82% had at least one incidental finding and 62% had one or more FDG-avid incidental findings. There were 46 “clinically actionable findings” for 40 participants overall; the reading radiologists recommended additional imaging for 28 findings and specialist consultation or procedural evaluation for 15 findings.
Details on these incidental findings were presented in a poster at the annual meeting of the American College of Rheumatology (ACR), held in Washington, DC.
The most common non–FDG-avid findings were pulmonary nodules, diverticulosis, cholelithiasis, sinus disease, and vascular calcifications. The most common FDG-avid findings were hypermetabolic lymphadenopathy, increased gastric/esophageal uptake, increased bowel uptake, and increased pharyngeal uptake.
In the related survey, 11 respondents (61%) said they returned any incidental findings to participants and 5 (28%) did not; the remaining 2 respondents did not know.
Across all study PIs, 22% felt that incidental findings were beneficial, 39% said they were potentially beneficial, and 11% said they were potentially detrimental. PIs that ranked incidental findings as potentially detrimental pointed to how these findings led to invasive additional testing.
“One of my subjects was found to have diverticulosis, which needed an invasive procedure to rule out malignancy,” one respondent wrote. “However, the subject had already had a colonoscopy months prior to the PET findings, which was still not deemed sufficient by the nuclear radiologist and GI consultant, so he had to have another colonoscopy, which was benign, but uncomfortable.”
Obligation to Return Findings
All investigators agreed that incidental findings should be shared with patients if they revealed a high-risk medical condition that can be treated; had important health implications such as premature death or substantial morbidity; and their health could be improved with proven preventive or therapeutic interventions.
There was more disagreement on whether to share that the FDG PET/CT revealed no findings or if the test revealed a finding without clear medical importance of which the research participant may not be aware.
An example of a less-specific finding could be something like increased FDG uptake in a particular area, like the bowel, Kang explained.
“The question is: What does that mean?” she said. “How do you interpret that?”
While some PIs might feel obligated to share all results with patients, sharing ambiguous incidental findings will likely not be helpful to the patient, said Arthur Caplan, PhD, of the Division of Medical Ethics at New York University (NYU) Grossman School of Medicine, New York City.
“Dealing in unknowns and uncertainties when you’re diagnosing doesn’t really do people very much good,” he said in an interview.
While most survey respondents said they were at least moderately obligated to disclose incidental research findings if a patient requests them, Caplan noted that it was ultimately the researchers’ decision.
“Patient preferences are something to take into account, but they’re not final. If the research team says, ‘we don’t know, it’s too uncertain, it’s too new,’ then I don’t think they have any obligation to return that [information],” he said. “You can’t tell somebody what you don’t understand.”
Conversely, the clearer the incidental finding, the stronger the obligation to share that information with research participants, he continued.
Need for a Standardized Approach
The TARGET study, like many research studies, left the management of incidental imaging findings to individual research sites and investigators.
It’s possible that different sites responded to these ambiguous clinical findings in different ways, Kang noted.
“If there’s a situation that’s difficult to interpret as it is, you can imagine that the resulting actions that may result from that can vary, too,” she said, which highlights the need for more specific and standardized guidance.
One way to approach this, Caplan noted, is establishing an agreed-upon approach for dealing with any incidental findings across all research sites before a study begins.
“If there is going to be a common study at many sites, then they should have a common response on what they are going to do,” he noted, and how they will share that information effectively with the research participants to ensure it’s understandable. However, in a lot of research studies, each site has its own approach.
“Right now, it’s all over the place and that shouldn’t be,” he said.
Institutional review boards (IRBs) could be one resource to help build detailed guidance on managing unclear incidental findings in future research, wrote Kang and coauthors.
“For incidental findings from whole body FDG PET/CT that are not clearly actionable or less straightforward, IRBs may consider requiring a certain level of follow-up for different categories or types of incidental findings or require that all incidental findings are reviewed by an independent group that would provide timely recommendations on the most appropriate return and management of those findings,” Kang and colleagues wrote. “With IRB guidance, very specific and detailed policies and procedures for returning and managing incidental findings should be established for every study, with consistency among the research sites of multicenter trials.”
The TARGET trial and survey were funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Kang reported receiving research funding from the National Institutes of Health and the Rheumatology Research Foundation. Caplan serves as a contributing author for this news organization and served on an independent bioethics panel for compassionate drug use that was funded by Johnson & Johnson through the NYU Grossman School of Medicine.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS CARE & RESEARCH
Microplastics Have Been Found in the Human Brain. Now What?
In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.
Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.
While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.
What Are the Major Health Concerns?
The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.
A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.
Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.
There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.
And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.
How Is the Brain Affected?
The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.
Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).
In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.
Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.
The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).
“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.
How Do Microplastics Reach the Brain?
Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.
This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.
“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.
Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.
In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.
While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.
The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.
“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.
Are Microplastics Regulated?
The most effective solution would be stricter regulations, Mauad said.
“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.
Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.
In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.
Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.
There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”
International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.
While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.
The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.
What Should Clinicians Know?
Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?
“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.
“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.
Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.
While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.
In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.
She would also like to see more studies on specific adverse health effects from microplastics in the body.
Mauad agreed.
“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.
The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.
Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.
While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.
What Are the Major Health Concerns?
The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.
A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.
Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.
There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.
And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.
How Is the Brain Affected?
The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.
Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).
In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.
Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.
The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).
“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.
How Do Microplastics Reach the Brain?
Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.
This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.
“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.
Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.
In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.
While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.
The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.
“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.
Are Microplastics Regulated?
The most effective solution would be stricter regulations, Mauad said.
“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.
Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.
In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.
Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.
There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”
International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.
While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.
The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.
What Should Clinicians Know?
Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?
“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.
“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.
Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.
While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.
In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.
She would also like to see more studies on specific adverse health effects from microplastics in the body.
Mauad agreed.
“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.
The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.
Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.
While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.
What Are the Major Health Concerns?
The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.
A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.
Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.
There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.
And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.
How Is the Brain Affected?
The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.
Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).
In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.
Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.
The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).
“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.
How Do Microplastics Reach the Brain?
Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.
This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.
“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.
Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.
In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.
While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.
The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.
“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.
Are Microplastics Regulated?
The most effective solution would be stricter regulations, Mauad said.
“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.
Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.
In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.
Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.
There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”
International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.
While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.
The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.
What Should Clinicians Know?
Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?
“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.
“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.
Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.
While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.
In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.
She would also like to see more studies on specific adverse health effects from microplastics in the body.
Mauad agreed.
“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.
The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New Gel Stops Severe Bleeding in Seconds
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
How Much Water Should We Drink in a Day?
This transcript has been edited for clarity.
It’s just about the easiest, safest medical advice you can give: “Drink more water.” You have a headache? Drink more water. Tired? Drink more water. Cold coming on? Drink more water. Tom Brady famously attributed his QB longevity to water drinking, among some other less ordinary practices.
I’m a nephrologist — a kidney doctor. I think about water all the time. I can tell you how your brain senses how much water is in your body and exactly how it communicates that information to your kidneys to control how dilute your urine is. I can explain the miraculous ability of the kidney to concentrate urine across a range from 50 mOsm/L to 1200 mOsm/L and the physiology that makes it all work.
But I can’t really tell you how much water you’re supposed to drink. And believe me, I get asked all the time.
I’m sure of a couple of things when it comes to water: You need to drink some. Though some animals, such as kangaroo rats, can get virtually all the water they need from the food they eat, we are not such animals. Without water, we die. I’m also sure that you can die from drinking too much water. Drinking excessive amounts of water dilutes the sodium in your blood, which messes with the electrical system in your brain and heart. I actually had a patient who went on a “water cleanse” and gave herself a seizure.
But, to be fair, assuming your kidneys are working reasonably well and you’re otherwise healthy, you’d need to drink around 20 liters of water a day to get into mortal trouble. The dose is the poison, as they say.
So, somewhere between zero and 20 liters of water is the amount you should be drinking in a day. That much I’m sure of.
But the evidence on where in that range you should target is actually pretty skimpy. You wouldn’t think so if you look at the online wellness influencers, with their Stanleys and their strict water intake regimens. You’d think the evidence for the benefits of drinking extra water is overwhelming.
The venerated National Academy of Medicine suggests that men drink thirteen 8 oz cups a day (that’s about 3 liters) and women drink nine 8 oz cups a day (a bit more than 2 liters). From what I can tell, this recommendation — like the old “8 cups of water per day” recommendation — is pulled out of thin air.
I’m not arguing that we shouldn’t drink water. Of course, water is important. I’m just wondering what data there are to really prove that drinking more water is better.
Fortunately, a team from UCSF has finally done the legwork for us. They break down the actual evidence in this paper, appearing in JAMA Network Open.
The team scoured the medical literature for randomized controlled trials of water intake. This is critical; we don’t want anecdotes about how clear someone’s skin became after they increased their water intake. We want icy cold, clear data. Randomized trials take a group of people and, at random, assign some to the intervention — in this case, drinking more water — and others to keep doing what they would normally do.
The team reviewed nearly 1500 papers but only 18 (!) met the rigorous criteria to be included in the analysis, as you can see from this flow chart.
This is the first important finding; not many high-quality studies have investigated how much water we should drink. Of course, water isn’t a prescription product, so funding is likely hard to come by. Can we do a trial of Dasani?
In any case, these 18 trials all looked at different outcomes of interest. Four studies looked at the impact of drinking more water on weight loss, two on fasting blood glucose, two on headache, two on urinary tract infection, two on kidney stones, and six studies on various other outcomes. None of the studies looked at energy, skin tone, or overall wellness, though one did measure a quality-of-life score.
And if I could sum up all these studies in a word, that word would be “meh.”
One of four weight loss studies showed that increasing water intake had no effect on weight loss. Two studies showed an effect, but drinking extra water was combined with a low-calorie diet, so that feels a bit like cheating to me. One study randomized participants to drink half a liter of water before meals, and that group did lose more weight than the control group — about a kilogram more over 12 weeks. That’s not exactly Ozempic.
For fasting blood glucose, although one trial suggested that higher premeal water intake lowered glucose levels, the other study (which looked just at increasing water overall) didn’t.
For headache — and, cards on the table here, I’m a big believer in water for headaches — one study showed nothing. The other showed that increasing water intake by 1.5 liters per day improved migraine-related quality of life but didn’t change the number of headache days per month.
For urinary tract infections, one positive trial and one negative one.
The best evidence comes from the kidney stone trials. Increasing water intake to achieve more than two liters of urine a day was associated with a significant reduction in kidney stone recurrence. I consider this a positive finding, more or less. You would be hard-pressed to find a kidney doctor who doesn’t think that people with a history of kidney stones should drink more water.
What about that quality-of-life study? They randomized participants to either drink 1.5 liters of extra water per day (intervention group) or not (control group). Six months later, the scores on the quality-of-life survey were no different between those two groups.
Thirsty yet?
So, what’s going on here? There are a few possibilities.
First, I need to point out that clinical trials are really hard. All the studies in this review were relatively small, with most enrolling fewer than 100 people. The effect of extra water would need to be pretty potent to detect it with those small samples.
I can’t help but point out that our bodies are actually exquisitely tuned to manage how much water we carry. As we lose water throughout the day from sweat and exhalation, our blood becomes a tiny bit more concentrated — the sodium level goes up. Our brains detect that and create a sensation we call thirst. Thirst is one of the most powerful drives we have. Animals, including humans, when thirsty, will choose water over food, over drugs, and over sex. It is incredibly hard to resist, and assuming that we have ready access to water, there is no need to resist it. We drink when we are thirsty. And that may be enough.
Of course, pushing beyond thirst is possible. We are sapient beings who can drink more than we want to. But what we can’t do, assuming our kidneys work, is hold onto that water. It passes right through us. In the case of preventing kidney stones, this is a good thing. Putting more water into your body leads to more water coming out — more dilute urine — which means it’s harder for stones to form.
But for all that other stuff? The wellness, the skin tone, and so on? It just doesn’t make much sense. If you drink an extra liter of water, you pee an extra liter of water. Net net? Zero.
Some folks will argue that the extra pee gets rid of extra toxins or something like that, but — sorry, kidney doctor Perry here again — that’s not how pee works. The clearance of toxins from the blood happens way upstream of where your urine is diluted or concentrated.
If you drink more, the same toxins come out, just with more water around them. In fact, one of the largest studies in this JAMA Network Open review assessed whether increasing water consumption in people with chronic kidney disease would improve kidney function. It didn’t.
I am left, then, with only a bit more confidence than when I began. Beyond that, it seems reasonable to trust the millions of years of evolution that have made water homeostasis central to life itself. Give yourself access to water. Drink when you’re thirsty. Drink a bit more if you’d like. But no need to push it. Your kidneys won’t let you anyway.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Connecticut. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
It’s just about the easiest, safest medical advice you can give: “Drink more water.” You have a headache? Drink more water. Tired? Drink more water. Cold coming on? Drink more water. Tom Brady famously attributed his QB longevity to water drinking, among some other less ordinary practices.
I’m a nephrologist — a kidney doctor. I think about water all the time. I can tell you how your brain senses how much water is in your body and exactly how it communicates that information to your kidneys to control how dilute your urine is. I can explain the miraculous ability of the kidney to concentrate urine across a range from 50 mOsm/L to 1200 mOsm/L and the physiology that makes it all work.
But I can’t really tell you how much water you’re supposed to drink. And believe me, I get asked all the time.
I’m sure of a couple of things when it comes to water: You need to drink some. Though some animals, such as kangaroo rats, can get virtually all the water they need from the food they eat, we are not such animals. Without water, we die. I’m also sure that you can die from drinking too much water. Drinking excessive amounts of water dilutes the sodium in your blood, which messes with the electrical system in your brain and heart. I actually had a patient who went on a “water cleanse” and gave herself a seizure.
But, to be fair, assuming your kidneys are working reasonably well and you’re otherwise healthy, you’d need to drink around 20 liters of water a day to get into mortal trouble. The dose is the poison, as they say.
So, somewhere between zero and 20 liters of water is the amount you should be drinking in a day. That much I’m sure of.
But the evidence on where in that range you should target is actually pretty skimpy. You wouldn’t think so if you look at the online wellness influencers, with their Stanleys and their strict water intake regimens. You’d think the evidence for the benefits of drinking extra water is overwhelming.
The venerated National Academy of Medicine suggests that men drink thirteen 8 oz cups a day (that’s about 3 liters) and women drink nine 8 oz cups a day (a bit more than 2 liters). From what I can tell, this recommendation — like the old “8 cups of water per day” recommendation — is pulled out of thin air.
I’m not arguing that we shouldn’t drink water. Of course, water is important. I’m just wondering what data there are to really prove that drinking more water is better.
Fortunately, a team from UCSF has finally done the legwork for us. They break down the actual evidence in this paper, appearing in JAMA Network Open.
The team scoured the medical literature for randomized controlled trials of water intake. This is critical; we don’t want anecdotes about how clear someone’s skin became after they increased their water intake. We want icy cold, clear data. Randomized trials take a group of people and, at random, assign some to the intervention — in this case, drinking more water — and others to keep doing what they would normally do.
The team reviewed nearly 1500 papers but only 18 (!) met the rigorous criteria to be included in the analysis, as you can see from this flow chart.
This is the first important finding; not many high-quality studies have investigated how much water we should drink. Of course, water isn’t a prescription product, so funding is likely hard to come by. Can we do a trial of Dasani?
In any case, these 18 trials all looked at different outcomes of interest. Four studies looked at the impact of drinking more water on weight loss, two on fasting blood glucose, two on headache, two on urinary tract infection, two on kidney stones, and six studies on various other outcomes. None of the studies looked at energy, skin tone, or overall wellness, though one did measure a quality-of-life score.
And if I could sum up all these studies in a word, that word would be “meh.”
One of four weight loss studies showed that increasing water intake had no effect on weight loss. Two studies showed an effect, but drinking extra water was combined with a low-calorie diet, so that feels a bit like cheating to me. One study randomized participants to drink half a liter of water before meals, and that group did lose more weight than the control group — about a kilogram more over 12 weeks. That’s not exactly Ozempic.
For fasting blood glucose, although one trial suggested that higher premeal water intake lowered glucose levels, the other study (which looked just at increasing water overall) didn’t.
For headache — and, cards on the table here, I’m a big believer in water for headaches — one study showed nothing. The other showed that increasing water intake by 1.5 liters per day improved migraine-related quality of life but didn’t change the number of headache days per month.
For urinary tract infections, one positive trial and one negative one.
The best evidence comes from the kidney stone trials. Increasing water intake to achieve more than two liters of urine a day was associated with a significant reduction in kidney stone recurrence. I consider this a positive finding, more or less. You would be hard-pressed to find a kidney doctor who doesn’t think that people with a history of kidney stones should drink more water.
What about that quality-of-life study? They randomized participants to either drink 1.5 liters of extra water per day (intervention group) or not (control group). Six months later, the scores on the quality-of-life survey were no different between those two groups.
Thirsty yet?
So, what’s going on here? There are a few possibilities.
First, I need to point out that clinical trials are really hard. All the studies in this review were relatively small, with most enrolling fewer than 100 people. The effect of extra water would need to be pretty potent to detect it with those small samples.
I can’t help but point out that our bodies are actually exquisitely tuned to manage how much water we carry. As we lose water throughout the day from sweat and exhalation, our blood becomes a tiny bit more concentrated — the sodium level goes up. Our brains detect that and create a sensation we call thirst. Thirst is one of the most powerful drives we have. Animals, including humans, when thirsty, will choose water over food, over drugs, and over sex. It is incredibly hard to resist, and assuming that we have ready access to water, there is no need to resist it. We drink when we are thirsty. And that may be enough.
Of course, pushing beyond thirst is possible. We are sapient beings who can drink more than we want to. But what we can’t do, assuming our kidneys work, is hold onto that water. It passes right through us. In the case of preventing kidney stones, this is a good thing. Putting more water into your body leads to more water coming out — more dilute urine — which means it’s harder for stones to form.
But for all that other stuff? The wellness, the skin tone, and so on? It just doesn’t make much sense. If you drink an extra liter of water, you pee an extra liter of water. Net net? Zero.
Some folks will argue that the extra pee gets rid of extra toxins or something like that, but — sorry, kidney doctor Perry here again — that’s not how pee works. The clearance of toxins from the blood happens way upstream of where your urine is diluted or concentrated.
If you drink more, the same toxins come out, just with more water around them. In fact, one of the largest studies in this JAMA Network Open review assessed whether increasing water consumption in people with chronic kidney disease would improve kidney function. It didn’t.
I am left, then, with only a bit more confidence than when I began. Beyond that, it seems reasonable to trust the millions of years of evolution that have made water homeostasis central to life itself. Give yourself access to water. Drink when you’re thirsty. Drink a bit more if you’d like. But no need to push it. Your kidneys won’t let you anyway.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Connecticut. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
It’s just about the easiest, safest medical advice you can give: “Drink more water.” You have a headache? Drink more water. Tired? Drink more water. Cold coming on? Drink more water. Tom Brady famously attributed his QB longevity to water drinking, among some other less ordinary practices.
I’m a nephrologist — a kidney doctor. I think about water all the time. I can tell you how your brain senses how much water is in your body and exactly how it communicates that information to your kidneys to control how dilute your urine is. I can explain the miraculous ability of the kidney to concentrate urine across a range from 50 mOsm/L to 1200 mOsm/L and the physiology that makes it all work.
But I can’t really tell you how much water you’re supposed to drink. And believe me, I get asked all the time.
I’m sure of a couple of things when it comes to water: You need to drink some. Though some animals, such as kangaroo rats, can get virtually all the water they need from the food they eat, we are not such animals. Without water, we die. I’m also sure that you can die from drinking too much water. Drinking excessive amounts of water dilutes the sodium in your blood, which messes with the electrical system in your brain and heart. I actually had a patient who went on a “water cleanse” and gave herself a seizure.
But, to be fair, assuming your kidneys are working reasonably well and you’re otherwise healthy, you’d need to drink around 20 liters of water a day to get into mortal trouble. The dose is the poison, as they say.
So, somewhere between zero and 20 liters of water is the amount you should be drinking in a day. That much I’m sure of.
But the evidence on where in that range you should target is actually pretty skimpy. You wouldn’t think so if you look at the online wellness influencers, with their Stanleys and their strict water intake regimens. You’d think the evidence for the benefits of drinking extra water is overwhelming.
The venerated National Academy of Medicine suggests that men drink thirteen 8 oz cups a day (that’s about 3 liters) and women drink nine 8 oz cups a day (a bit more than 2 liters). From what I can tell, this recommendation — like the old “8 cups of water per day” recommendation — is pulled out of thin air.
I’m not arguing that we shouldn’t drink water. Of course, water is important. I’m just wondering what data there are to really prove that drinking more water is better.
Fortunately, a team from UCSF has finally done the legwork for us. They break down the actual evidence in this paper, appearing in JAMA Network Open.
The team scoured the medical literature for randomized controlled trials of water intake. This is critical; we don’t want anecdotes about how clear someone’s skin became after they increased their water intake. We want icy cold, clear data. Randomized trials take a group of people and, at random, assign some to the intervention — in this case, drinking more water — and others to keep doing what they would normally do.
The team reviewed nearly 1500 papers but only 18 (!) met the rigorous criteria to be included in the analysis, as you can see from this flow chart.
This is the first important finding; not many high-quality studies have investigated how much water we should drink. Of course, water isn’t a prescription product, so funding is likely hard to come by. Can we do a trial of Dasani?
In any case, these 18 trials all looked at different outcomes of interest. Four studies looked at the impact of drinking more water on weight loss, two on fasting blood glucose, two on headache, two on urinary tract infection, two on kidney stones, and six studies on various other outcomes. None of the studies looked at energy, skin tone, or overall wellness, though one did measure a quality-of-life score.
And if I could sum up all these studies in a word, that word would be “meh.”
One of four weight loss studies showed that increasing water intake had no effect on weight loss. Two studies showed an effect, but drinking extra water was combined with a low-calorie diet, so that feels a bit like cheating to me. One study randomized participants to drink half a liter of water before meals, and that group did lose more weight than the control group — about a kilogram more over 12 weeks. That’s not exactly Ozempic.
For fasting blood glucose, although one trial suggested that higher premeal water intake lowered glucose levels, the other study (which looked just at increasing water overall) didn’t.
For headache — and, cards on the table here, I’m a big believer in water for headaches — one study showed nothing. The other showed that increasing water intake by 1.5 liters per day improved migraine-related quality of life but didn’t change the number of headache days per month.
For urinary tract infections, one positive trial and one negative one.
The best evidence comes from the kidney stone trials. Increasing water intake to achieve more than two liters of urine a day was associated with a significant reduction in kidney stone recurrence. I consider this a positive finding, more or less. You would be hard-pressed to find a kidney doctor who doesn’t think that people with a history of kidney stones should drink more water.
What about that quality-of-life study? They randomized participants to either drink 1.5 liters of extra water per day (intervention group) or not (control group). Six months later, the scores on the quality-of-life survey were no different between those two groups.
Thirsty yet?
So, what’s going on here? There are a few possibilities.
First, I need to point out that clinical trials are really hard. All the studies in this review were relatively small, with most enrolling fewer than 100 people. The effect of extra water would need to be pretty potent to detect it with those small samples.
I can’t help but point out that our bodies are actually exquisitely tuned to manage how much water we carry. As we lose water throughout the day from sweat and exhalation, our blood becomes a tiny bit more concentrated — the sodium level goes up. Our brains detect that and create a sensation we call thirst. Thirst is one of the most powerful drives we have. Animals, including humans, when thirsty, will choose water over food, over drugs, and over sex. It is incredibly hard to resist, and assuming that we have ready access to water, there is no need to resist it. We drink when we are thirsty. And that may be enough.
Of course, pushing beyond thirst is possible. We are sapient beings who can drink more than we want to. But what we can’t do, assuming our kidneys work, is hold onto that water. It passes right through us. In the case of preventing kidney stones, this is a good thing. Putting more water into your body leads to more water coming out — more dilute urine — which means it’s harder for stones to form.
But for all that other stuff? The wellness, the skin tone, and so on? It just doesn’t make much sense. If you drink an extra liter of water, you pee an extra liter of water. Net net? Zero.
Some folks will argue that the extra pee gets rid of extra toxins or something like that, but — sorry, kidney doctor Perry here again — that’s not how pee works. The clearance of toxins from the blood happens way upstream of where your urine is diluted or concentrated.
If you drink more, the same toxins come out, just with more water around them. In fact, one of the largest studies in this JAMA Network Open review assessed whether increasing water consumption in people with chronic kidney disease would improve kidney function. It didn’t.
I am left, then, with only a bit more confidence than when I began. Beyond that, it seems reasonable to trust the millions of years of evolution that have made water homeostasis central to life itself. Give yourself access to water. Drink when you’re thirsty. Drink a bit more if you’d like. But no need to push it. Your kidneys won’t let you anyway.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Connecticut. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.