Individuals with migraine demonstrated a different dry eye (DE) symptom, yet a similar DE sign profile when compared with those without migraine, a new study found. The prospective cross-sectional study of individuals with DE symptoms evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction. Among the details:

• Of 250 individuals, 31 met International Classification of Headache Disorders criteria for migraine based on a validated screen.
• Those with migraine were significantly younger and more likely to be female vs controls.
• Individuals with migraine had more severe DE symptoms and ocular pain vs controls.
• DE symptoms in those with migraine may be driven by nerve dysfunction as opposed to ocular surface abnormalities.

Farhangi M, et al. Individuals with migraine have a different dry eye symptom profile than individuals without migraine. [Published online ahead of print April 30, 2019]. Br J Opthalmol. doi: 10.1136/bjophthalmol-2018-313471.

Individuals with migraine demonstrated a different dry eye (DE) symptom, yet a similar DE sign profile when compared with those without migraine, a new study found. The prospective cross-sectional study of individuals with DE symptoms evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction. Among the details:

• Of 250 individuals, 31 met International Classification of Headache Disorders criteria for migraine based on a validated screen.
• Those with migraine were significantly younger and more likely to be female vs controls.
• Individuals with migraine had more severe DE symptoms and ocular pain vs controls.
• DE symptoms in those with migraine may be driven by nerve dysfunction as opposed to ocular surface abnormalities.

Farhangi M, et al. Individuals with migraine have a different dry eye symptom profile than individuals without migraine. [Published online ahead of print April 30, 2019]. Br J Opthalmol. doi: 10.1136/bjophthalmol-2018-313471.

Individuals with migraine demonstrated a different dry eye (DE) symptom, yet a similar DE sign profile when compared with those without migraine, a new study found. The prospective cross-sectional study of individuals with DE symptoms evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction. Among the details:

• Of 250 individuals, 31 met International Classification of Headache Disorders criteria for migraine based on a validated screen.
• Those with migraine were significantly younger and more likely to be female vs controls.
• Individuals with migraine had more severe DE symptoms and ocular pain vs controls.
• DE symptoms in those with migraine may be driven by nerve dysfunction as opposed to ocular surface abnormalities.

Farhangi M, et al. Individuals with migraine have a different dry eye symptom profile than individuals without migraine. [Published online ahead of print April 30, 2019]. Br J Opthalmol. doi: 10.1136/bjophthalmol-2018-313471.

Atypical Interactions of Cortical Networks in Chronic Migraine

The severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks in patients with chronic migraine, a new study found. Twenty patients with chronic migraine (CM) without preventive therapy, or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). Researchers used MRI to collect resting-state data in 3 selected networks, identified using group independent component analysis (ICA): the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS). They found:

• Compared to HC, patients with CM had significantly reduced functional connectivity between the DMN and the ECN.
• The DAS showed significantly stronger functional connectivity (FC) with the DMN and weaker FC with the ECN.
• The higher the severity of the headache, the increased strength of DAD connectivity, and the lower the strength of the ECN connectivity.

Coppola G, et al. Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study. [Published online ahead of print May 28, 2019]. Neurology. doi: 10.1212/WNL.0000000000007577.

Atypical Interactions of Cortical Networks in Chronic Migraine

The severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks in patients with chronic migraine, a new study found. Twenty patients with chronic migraine (CM) without preventive therapy, or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). Researchers used MRI to collect resting-state data in 3 selected networks, identified using group independent component analysis (ICA): the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS). They found:

• Compared to HC, patients with CM had significantly reduced functional connectivity between the DMN and the ECN.
• The DAS showed significantly stronger functional connectivity (FC) with the DMN and weaker FC with the ECN.
• The higher the severity of the headache, the increased strength of DAD connectivity, and the lower the strength of the ECN connectivity.

Coppola G, et al. Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study. [Published online ahead of print May 28, 2019]. Neurology. doi: 10.1212/WNL.0000000000007577.

Atypical Interactions of Cortical Networks in Chronic Migraine

The severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks in patients with chronic migraine, a new study found. Twenty patients with chronic migraine (CM) without preventive therapy, or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). Researchers used MRI to collect resting-state data in 3 selected networks, identified using group independent component analysis (ICA): the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS). They found:

• Compared to HC, patients with CM had significantly reduced functional connectivity between the DMN and the ECN.
• The DAS showed significantly stronger functional connectivity (FC) with the DMN and weaker FC with the ECN.
• The higher the severity of the headache, the increased strength of DAD connectivity, and the lower the strength of the ECN connectivity.

Coppola G, et al. Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study. [Published online ahead of print May 28, 2019]. Neurology. doi: 10.1212/WNL.0000000000007577.

When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?

I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.

I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.

Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.

In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.

There are several biases of overconfidence. One is the expert trap: You believe you are an expert or correct, but you are wrong and you don’t see it. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.

Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.

If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.

By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?

I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.

I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.

Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.

In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.

There are several biases of overconfidence. One is the expert trap: You believe you are an expert or correct, but you are wrong and you don’t see it. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.

Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.

If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.

By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?

I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.

I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.

Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.

In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.

There are several biases of overconfidence. One is the expert trap: You believe you are an expert or correct, but you are wrong and you don’t see it. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.

Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.

If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.

By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.

Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.

“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.

[email protected]

SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.

Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.

Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.

“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.

[email protected]

SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.

Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.

Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.

“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.

[email protected]

SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Women with epithelial ovarian cancer or BRCA1 mutational status were more likely to present with a community type O cervicovaginal microbiota relative to age-matched controls, according to a case-control analysis.

The results suggest that the composition of the cervicovaginal microbiome may have a key role in ovarian carcinogenesis. In addition, dysbiosis could be an important risk factor in women at high risk for the disease.

“Our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome,” wrote Nuno R Nené, PhD, of University College London, and colleagues. Their report is in The Lancet Oncology.

The researchers conducted a case-control study of adult females located in five European countries. Study participants were divided into two sets that consisted of 176 females with ovarian cancer and 109 females with a BRCA1 mutation, but without a diagnosis of ovarian cancer.

The two sets were matched with a combination of healthy controls and others with benign gynecologic disorders. Each cohort was split into females younger than 50 years and those over age 50.

In the analysis, females younger than 50 years with ovarian cancer were more likely to have a community type O microbiota relative to age-matched controls (adjusted odds ratio, 2.80; P = .020).

In the BRCA set, women with a BRCA1 mutation who were younger than 50 years were also more likely to present with a community type O microbiota than were wild type age-matched controls (adjusted odds ratio, 2.79; P = .012).

“In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status,” the researchers wrote.

They acknowledged that a key limitation of the study was the homogenous patient population. Since the vaginal microbiome can vary based on ethnicity, the generalizability of the results may be limited.

“Our findings warrant further detailed analyses of the vaginal microbiome, especially in high-risk women,” they concluded.

The study was funded by the EU’s Horizon 2020 Research and Innovation Programme, the EU’s Horizon 2020 European Research Council Programme, and The Eve Appeal. The authors reported financial affiliations with Eurofins, AstraZeneca, Biocad, Clovis, Pharmamar, Roche, Takeda, and Tesaro.

SOURCE: Nené NR et al. Lancet Oncol. 2019 Jul 9. doi: 10.1016/S1470-2045(19)30340-7.

Women with epithelial ovarian cancer or BRCA1 mutational status were more likely to present with a community type O cervicovaginal microbiota relative to age-matched controls, according to a case-control analysis.

The results suggest that the composition of the cervicovaginal microbiome may have a key role in ovarian carcinogenesis. In addition, dysbiosis could be an important risk factor in women at high risk for the disease.

“Our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome,” wrote Nuno R Nené, PhD, of University College London, and colleagues. Their report is in The Lancet Oncology.

The researchers conducted a case-control study of adult females located in five European countries. Study participants were divided into two sets that consisted of 176 females with ovarian cancer and 109 females with a BRCA1 mutation, but without a diagnosis of ovarian cancer.

The two sets were matched with a combination of healthy controls and others with benign gynecologic disorders. Each cohort was split into females younger than 50 years and those over age 50.

In the analysis, females younger than 50 years with ovarian cancer were more likely to have a community type O microbiota relative to age-matched controls (adjusted odds ratio, 2.80; P = .020).

In the BRCA set, women with a BRCA1 mutation who were younger than 50 years were also more likely to present with a community type O microbiota than were wild type age-matched controls (adjusted odds ratio, 2.79; P = .012).

“In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status,” the researchers wrote.

They acknowledged that a key limitation of the study was the homogenous patient population. Since the vaginal microbiome can vary based on ethnicity, the generalizability of the results may be limited.

“Our findings warrant further detailed analyses of the vaginal microbiome, especially in high-risk women,” they concluded.

The study was funded by the EU’s Horizon 2020 Research and Innovation Programme, the EU’s Horizon 2020 European Research Council Programme, and The Eve Appeal. The authors reported financial affiliations with Eurofins, AstraZeneca, Biocad, Clovis, Pharmamar, Roche, Takeda, and Tesaro.

SOURCE: Nené NR et al. Lancet Oncol. 2019 Jul 9. doi: 10.1016/S1470-2045(19)30340-7.

Women with epithelial ovarian cancer or BRCA1 mutational status were more likely to present with a community type O cervicovaginal microbiota relative to age-matched controls, according to a case-control analysis.

The results suggest that the composition of the cervicovaginal microbiome may have a key role in ovarian carcinogenesis. In addition, dysbiosis could be an important risk factor in women at high risk for the disease.

“Our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome,” wrote Nuno R Nené, PhD, of University College London, and colleagues. Their report is in The Lancet Oncology.

The researchers conducted a case-control study of adult females located in five European countries. Study participants were divided into two sets that consisted of 176 females with ovarian cancer and 109 females with a BRCA1 mutation, but without a diagnosis of ovarian cancer.

The two sets were matched with a combination of healthy controls and others with benign gynecologic disorders. Each cohort was split into females younger than 50 years and those over age 50.

In the analysis, females younger than 50 years with ovarian cancer were more likely to have a community type O microbiota relative to age-matched controls (adjusted odds ratio, 2.80; P = .020).

In the BRCA set, women with a BRCA1 mutation who were younger than 50 years were also more likely to present with a community type O microbiota than were wild type age-matched controls (adjusted odds ratio, 2.79; P = .012).

“In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status,” the researchers wrote.

They acknowledged that a key limitation of the study was the homogenous patient population. Since the vaginal microbiome can vary based on ethnicity, the generalizability of the results may be limited.

“Our findings warrant further detailed analyses of the vaginal microbiome, especially in high-risk women,” they concluded.

The study was funded by the EU’s Horizon 2020 Research and Innovation Programme, the EU’s Horizon 2020 European Research Council Programme, and The Eve Appeal. The authors reported financial affiliations with Eurofins, AstraZeneca, Biocad, Clovis, Pharmamar, Roche, Takeda, and Tesaro.

SOURCE: Nené NR et al. Lancet Oncol. 2019 Jul 9. doi: 10.1016/S1470-2045(19)30340-7.

Health insurers that cover millions of seniors have overcharged Medicare by nearly $30 billion the past 3 years alone, but federal officials say they are moving ahead with long-delayed plans to recoup at least part of the money.

Officials have known for years that some Medicare Advantage plans overbill the government by exaggerating how sick their members are or by charging Medicare for treatment of serious medical conditions they cannot prove their members have.

Getting refunds from the health plans has proved daunting, however. Officials with the Centers for Medicare & Medicaid Services repeatedly have postponed, or backed off, efforts to crack down on billing abuses and mistakes by the increasingly popular Medicare Advantage health plans offered by private health insurers under contract with Medicare. Today, such plans treat over 22 million seniors, more than 1 in 3 people on Medicare.

Now CMS is trying again, proposing a series of enhanced audits tailored to claw back $1 billion in Medicare Advantage overpayments by 2020 – just a tenth of what it estimates the plans overcharge the government in a given year.

At the same time, the Department of Health and Human Services Inspector General’s Office has launched a separate nationwide round of Medicare Advantage audits.

As in past years, such scrutiny faces an onslaught of criticism from the insurance industry, which argues the CMS audits especially are technically unsound and unfair and could jeopardize medical services for seniors.

America’s Health Insurance Plans, an industry trade group, blasted the CMS audit design when details emerged last fall, calling it “fatally flawed.”

Insurer Cigna Corp. warned in a May financial filing: “If adopted in its current form, [the audits] could have a detrimental impact” on all Medicare Advantage plans and “affect the ability of plans to deliver high quality care.”

But former Sen. Claire McCaskill, a Missouri Democrat who now works as a political analyst, said officials must move past powerful lobbying efforts to hold health insurers accountable and demand refunds for “inappropriate” billings.

“There’s a lot of things that could cause Medicare to go broke. This would be one of the contributing factors,” she said. “Ten billion dollars a year is real money.”
 

Catching overbilling with a wider net

In the overpayment dispute, health plans want CMS to scale back – if not kill off – an enhanced audit tool that, for the first time, could force insurers to cough up millions in improper payments they’ve received.

For over a decade, audits have been little more than an irritant to insurers because most plans go years without being chosen for review and often pay only a few hundred thousand dollars in refunds as a consequence. When auditors uncover errors in the medical records of patients they paid the companies to treat, CMS has simply required a rebate for those patients for just the year audited – relatively small sums for plans with thousands of members.

The latest CMS proposal would raise those stakes enormously by extrapolating error rates found in a random sample of 200 patients to the plan’s full membership – a technique expected to trigger many multimillion-dollar penalties. Though controversial, extrapolation is common in medical fraud investigations – except for investigations into Medicare Advantage. Since 2007, the industry has successfully challenged the extrapolation method and, as a result, largely avoided accountability for pervasive billing errors.

“The public has a substantial interest in the recoupment of millions of dollars of public money improperly paid to health insurers,” CMS wrote in a Federal Register notice late last year announcing its renewed attempt at using extrapolation.
 

Penalties in limbo

In a written response to questions posed by Kaiser Health News, CMS officials said the agency has already conducted 90 of those enhanced audits for payments made in 2011, 2012 and 2013 – and expects to collect $650 million in extrapolated penalties as a result.

Though that figure reflects only a minute percentage of actual losses to taxpayers from overpayments, it would be a huge escalation for CMS. Previous Medicare Advantage audits have recouped a total of about $14 million, far less than it cost to conduct them, federal records show.

Though CMS has disclosed the names of the health plans in the crossfire, it has not yet told them how much each owes, officials said. CMS declined to say when, or if, they would make the results public.

This year, CMS is starting audits for 2014 and 2015, 30 per year, targeting about 5% of the 600 plans annually.

This spring, CMS announced it would extend until the end of August the audit proposal’s public comment period, which was supposed to end in April. That could be a signal the agency might be looking more closely at industry objections.

Health care industry consultant Jessica Smith said CMS might be taking additional time to make sure the audit protocol can pass muster. “Once they have their ducks in a row, CMS will come back hard at the health plans. There is so much money tied to this.”

But Sean Creighton, a former senior CMS official who now advises the industry for health care consultant Avalere Health, said payment error rates have been dropping because many health plans “are trying as hard as they can to become compliant.”

Still, audits are continuing to find mistakes. The first HHS inspector general audit, released in late April, found that Missouri-based Essence Healthcare Inc. had failed to justify fees for dozens of patients it had covered for strokes or depression. Essence denied any wrongdoing but agreed it should refund $158,904 in overcharges for those patients and ferret out any other errors.

Essence also faces a pending whistle-blower suit filed by Charles Rasmussen, a Branson, Mo., doctor who alleges the health plan illegally boosted profits by overstating the severity of patients’ medical conditions. Essence has called the allegations “wholly without merit” and “baseless.”

Essence started as a St. Louis physician group, then grew into a broader holding company backed by prominent Silicon Valley venture capitalist John Doerr with his brother, St. Louis doctor and software designer Thomas Doerr, in 2007. Neither would comment on the allegations.
 

How we got here

CMS uses a billing formula called a “risk score” to pay for each Medicare Advantage member. The formula pays higher rates for sicker patients than for people in good health.

Congress approved risk scoring in 2003 to ensure health plans did not shy away from taking sick patients who could incur higher-than-usual costs from hospitals and other medical facilities. But some insurers quickly found ways to boost risk scores – and their revenues.

In 2007, after several years of running Medicare Advantage as what one CMS official dubbed an “honor system,” the agency launched “Risk Adjustment Data Validation,” or RADV, audits. The idea was to cut down on undeserved payments that cost CMS nearly $30 billion over the past 3 years.

The audits of 37 health plans revealed that on average auditors could confirm just 60% of the more than 20,000 medical conditions CMS had paid the plans to treat.

Extra payments to plans that had claimed some of its diabetic patients had complications, such as eye or kidney problems, were reduced or invalidated in nearly half the cases. The overpayments exceeded $10,000 a year for more than 150 patients, though health plans disputed some of the findings.

But CMS kept the findings under wraps until the Center for Public Integrity sued the agency under the Freedom of Information Act to make them public.

Despite the alarming results, CMS conducted no audits for payments made during 2008, 2009 and 2010 as they faced industry backlash over CMS’ authority to conduct them, and the threat of extrapolated repayments. Some inside the agency also worried that health plans would abandon the Medicare Advantage program if CMS pressed them too hard, records released through the FOIA lawsuit show.

CMS officials resumed the audits for 2011 and expected to finish them and assess penalties by the end of 2016. That has yet to happen amid the continuing protests from the industry. Insurers want CMS to adjust downward any extrapolated penalties to account for coding errors that exist in standard Medicare. CMS stands behind its method – at least for now.

At a minimum, argues AHIP, the health insurers association, CMS should back off extrapolation for the 90 audits for 2011-13 and apply it for 2014 and onward. Should CMS agree, it would write off more than half a billion dollars that could be recovered for the U.S. Treasury.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Health insurers that cover millions of seniors have overcharged Medicare by nearly $30 billion the past 3 years alone, but federal officials say they are moving ahead with long-delayed plans to recoup at least part of the money.

Officials have known for years that some Medicare Advantage plans overbill the government by exaggerating how sick their members are or by charging Medicare for treatment of serious medical conditions they cannot prove their members have.

Getting refunds from the health plans has proved daunting, however. Officials with the Centers for Medicare & Medicaid Services repeatedly have postponed, or backed off, efforts to crack down on billing abuses and mistakes by the increasingly popular Medicare Advantage health plans offered by private health insurers under contract with Medicare. Today, such plans treat over 22 million seniors, more than 1 in 3 people on Medicare.

Now CMS is trying again, proposing a series of enhanced audits tailored to claw back $1 billion in Medicare Advantage overpayments by 2020 – just a tenth of what it estimates the plans overcharge the government in a given year.

At the same time, the Department of Health and Human Services Inspector General’s Office has launched a separate nationwide round of Medicare Advantage audits.

As in past years, such scrutiny faces an onslaught of criticism from the insurance industry, which argues the CMS audits especially are technically unsound and unfair and could jeopardize medical services for seniors.

America’s Health Insurance Plans, an industry trade group, blasted the CMS audit design when details emerged last fall, calling it “fatally flawed.”

Insurer Cigna Corp. warned in a May financial filing: “If adopted in its current form, [the audits] could have a detrimental impact” on all Medicare Advantage plans and “affect the ability of plans to deliver high quality care.”

But former Sen. Claire McCaskill, a Missouri Democrat who now works as a political analyst, said officials must move past powerful lobbying efforts to hold health insurers accountable and demand refunds for “inappropriate” billings.

“There’s a lot of things that could cause Medicare to go broke. This would be one of the contributing factors,” she said. “Ten billion dollars a year is real money.”
 

Catching overbilling with a wider net

In the overpayment dispute, health plans want CMS to scale back – if not kill off – an enhanced audit tool that, for the first time, could force insurers to cough up millions in improper payments they’ve received.

For over a decade, audits have been little more than an irritant to insurers because most plans go years without being chosen for review and often pay only a few hundred thousand dollars in refunds as a consequence. When auditors uncover errors in the medical records of patients they paid the companies to treat, CMS has simply required a rebate for those patients for just the year audited – relatively small sums for plans with thousands of members.

The latest CMS proposal would raise those stakes enormously by extrapolating error rates found in a random sample of 200 patients to the plan’s full membership – a technique expected to trigger many multimillion-dollar penalties. Though controversial, extrapolation is common in medical fraud investigations – except for investigations into Medicare Advantage. Since 2007, the industry has successfully challenged the extrapolation method and, as a result, largely avoided accountability for pervasive billing errors.

“The public has a substantial interest in the recoupment of millions of dollars of public money improperly paid to health insurers,” CMS wrote in a Federal Register notice late last year announcing its renewed attempt at using extrapolation.
 

Penalties in limbo

In a written response to questions posed by Kaiser Health News, CMS officials said the agency has already conducted 90 of those enhanced audits for payments made in 2011, 2012 and 2013 – and expects to collect $650 million in extrapolated penalties as a result.

Though that figure reflects only a minute percentage of actual losses to taxpayers from overpayments, it would be a huge escalation for CMS. Previous Medicare Advantage audits have recouped a total of about $14 million, far less than it cost to conduct them, federal records show.

Though CMS has disclosed the names of the health plans in the crossfire, it has not yet told them how much each owes, officials said. CMS declined to say when, or if, they would make the results public.

This year, CMS is starting audits for 2014 and 2015, 30 per year, targeting about 5% of the 600 plans annually.

This spring, CMS announced it would extend until the end of August the audit proposal’s public comment period, which was supposed to end in April. That could be a signal the agency might be looking more closely at industry objections.

Health care industry consultant Jessica Smith said CMS might be taking additional time to make sure the audit protocol can pass muster. “Once they have their ducks in a row, CMS will come back hard at the health plans. There is so much money tied to this.”

But Sean Creighton, a former senior CMS official who now advises the industry for health care consultant Avalere Health, said payment error rates have been dropping because many health plans “are trying as hard as they can to become compliant.”

Still, audits are continuing to find mistakes. The first HHS inspector general audit, released in late April, found that Missouri-based Essence Healthcare Inc. had failed to justify fees for dozens of patients it had covered for strokes or depression. Essence denied any wrongdoing but agreed it should refund $158,904 in overcharges for those patients and ferret out any other errors.

Essence also faces a pending whistle-blower suit filed by Charles Rasmussen, a Branson, Mo., doctor who alleges the health plan illegally boosted profits by overstating the severity of patients’ medical conditions. Essence has called the allegations “wholly without merit” and “baseless.”

Essence started as a St. Louis physician group, then grew into a broader holding company backed by prominent Silicon Valley venture capitalist John Doerr with his brother, St. Louis doctor and software designer Thomas Doerr, in 2007. Neither would comment on the allegations.
 

How we got here

CMS uses a billing formula called a “risk score” to pay for each Medicare Advantage member. The formula pays higher rates for sicker patients than for people in good health.

Congress approved risk scoring in 2003 to ensure health plans did not shy away from taking sick patients who could incur higher-than-usual costs from hospitals and other medical facilities. But some insurers quickly found ways to boost risk scores – and their revenues.

In 2007, after several years of running Medicare Advantage as what one CMS official dubbed an “honor system,” the agency launched “Risk Adjustment Data Validation,” or RADV, audits. The idea was to cut down on undeserved payments that cost CMS nearly $30 billion over the past 3 years.

The audits of 37 health plans revealed that on average auditors could confirm just 60% of the more than 20,000 medical conditions CMS had paid the plans to treat.

Extra payments to plans that had claimed some of its diabetic patients had complications, such as eye or kidney problems, were reduced or invalidated in nearly half the cases. The overpayments exceeded $10,000 a year for more than 150 patients, though health plans disputed some of the findings.

But CMS kept the findings under wraps until the Center for Public Integrity sued the agency under the Freedom of Information Act to make them public.

Despite the alarming results, CMS conducted no audits for payments made during 2008, 2009 and 2010 as they faced industry backlash over CMS’ authority to conduct them, and the threat of extrapolated repayments. Some inside the agency also worried that health plans would abandon the Medicare Advantage program if CMS pressed them too hard, records released through the FOIA lawsuit show.

CMS officials resumed the audits for 2011 and expected to finish them and assess penalties by the end of 2016. That has yet to happen amid the continuing protests from the industry. Insurers want CMS to adjust downward any extrapolated penalties to account for coding errors that exist in standard Medicare. CMS stands behind its method – at least for now.

At a minimum, argues AHIP, the health insurers association, CMS should back off extrapolation for the 90 audits for 2011-13 and apply it for 2014 and onward. Should CMS agree, it would write off more than half a billion dollars that could be recovered for the U.S. Treasury.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Health insurers that cover millions of seniors have overcharged Medicare by nearly $30 billion the past 3 years alone, but federal officials say they are moving ahead with long-delayed plans to recoup at least part of the money.

Officials have known for years that some Medicare Advantage plans overbill the government by exaggerating how sick their members are or by charging Medicare for treatment of serious medical conditions they cannot prove their members have.

Getting refunds from the health plans has proved daunting, however. Officials with the Centers for Medicare & Medicaid Services repeatedly have postponed, or backed off, efforts to crack down on billing abuses and mistakes by the increasingly popular Medicare Advantage health plans offered by private health insurers under contract with Medicare. Today, such plans treat over 22 million seniors, more than 1 in 3 people on Medicare.

Now CMS is trying again, proposing a series of enhanced audits tailored to claw back $1 billion in Medicare Advantage overpayments by 2020 – just a tenth of what it estimates the plans overcharge the government in a given year.

At the same time, the Department of Health and Human Services Inspector General’s Office has launched a separate nationwide round of Medicare Advantage audits.

As in past years, such scrutiny faces an onslaught of criticism from the insurance industry, which argues the CMS audits especially are technically unsound and unfair and could jeopardize medical services for seniors.

America’s Health Insurance Plans, an industry trade group, blasted the CMS audit design when details emerged last fall, calling it “fatally flawed.”

Insurer Cigna Corp. warned in a May financial filing: “If adopted in its current form, [the audits] could have a detrimental impact” on all Medicare Advantage plans and “affect the ability of plans to deliver high quality care.”

But former Sen. Claire McCaskill, a Missouri Democrat who now works as a political analyst, said officials must move past powerful lobbying efforts to hold health insurers accountable and demand refunds for “inappropriate” billings.

“There’s a lot of things that could cause Medicare to go broke. This would be one of the contributing factors,” she said. “Ten billion dollars a year is real money.”
 

Catching overbilling with a wider net

In the overpayment dispute, health plans want CMS to scale back – if not kill off – an enhanced audit tool that, for the first time, could force insurers to cough up millions in improper payments they’ve received.

For over a decade, audits have been little more than an irritant to insurers because most plans go years without being chosen for review and often pay only a few hundred thousand dollars in refunds as a consequence. When auditors uncover errors in the medical records of patients they paid the companies to treat, CMS has simply required a rebate for those patients for just the year audited – relatively small sums for plans with thousands of members.

The latest CMS proposal would raise those stakes enormously by extrapolating error rates found in a random sample of 200 patients to the plan’s full membership – a technique expected to trigger many multimillion-dollar penalties. Though controversial, extrapolation is common in medical fraud investigations – except for investigations into Medicare Advantage. Since 2007, the industry has successfully challenged the extrapolation method and, as a result, largely avoided accountability for pervasive billing errors.

“The public has a substantial interest in the recoupment of millions of dollars of public money improperly paid to health insurers,” CMS wrote in a Federal Register notice late last year announcing its renewed attempt at using extrapolation.
 

Penalties in limbo

In a written response to questions posed by Kaiser Health News, CMS officials said the agency has already conducted 90 of those enhanced audits for payments made in 2011, 2012 and 2013 – and expects to collect $650 million in extrapolated penalties as a result.

Though that figure reflects only a minute percentage of actual losses to taxpayers from overpayments, it would be a huge escalation for CMS. Previous Medicare Advantage audits have recouped a total of about $14 million, far less than it cost to conduct them, federal records show.

Though CMS has disclosed the names of the health plans in the crossfire, it has not yet told them how much each owes, officials said. CMS declined to say when, or if, they would make the results public.

This year, CMS is starting audits for 2014 and 2015, 30 per year, targeting about 5% of the 600 plans annually.

This spring, CMS announced it would extend until the end of August the audit proposal’s public comment period, which was supposed to end in April. That could be a signal the agency might be looking more closely at industry objections.

Health care industry consultant Jessica Smith said CMS might be taking additional time to make sure the audit protocol can pass muster. “Once they have their ducks in a row, CMS will come back hard at the health plans. There is so much money tied to this.”

But Sean Creighton, a former senior CMS official who now advises the industry for health care consultant Avalere Health, said payment error rates have been dropping because many health plans “are trying as hard as they can to become compliant.”

Still, audits are continuing to find mistakes. The first HHS inspector general audit, released in late April, found that Missouri-based Essence Healthcare Inc. had failed to justify fees for dozens of patients it had covered for strokes or depression. Essence denied any wrongdoing but agreed it should refund $158,904 in overcharges for those patients and ferret out any other errors.

Essence also faces a pending whistle-blower suit filed by Charles Rasmussen, a Branson, Mo., doctor who alleges the health plan illegally boosted profits by overstating the severity of patients’ medical conditions. Essence has called the allegations “wholly without merit” and “baseless.”

Essence started as a St. Louis physician group, then grew into a broader holding company backed by prominent Silicon Valley venture capitalist John Doerr with his brother, St. Louis doctor and software designer Thomas Doerr, in 2007. Neither would comment on the allegations.
 

How we got here

CMS uses a billing formula called a “risk score” to pay for each Medicare Advantage member. The formula pays higher rates for sicker patients than for people in good health.

Congress approved risk scoring in 2003 to ensure health plans did not shy away from taking sick patients who could incur higher-than-usual costs from hospitals and other medical facilities. But some insurers quickly found ways to boost risk scores – and their revenues.

In 2007, after several years of running Medicare Advantage as what one CMS official dubbed an “honor system,” the agency launched “Risk Adjustment Data Validation,” or RADV, audits. The idea was to cut down on undeserved payments that cost CMS nearly $30 billion over the past 3 years.

The audits of 37 health plans revealed that on average auditors could confirm just 60% of the more than 20,000 medical conditions CMS had paid the plans to treat.

Extra payments to plans that had claimed some of its diabetic patients had complications, such as eye or kidney problems, were reduced or invalidated in nearly half the cases. The overpayments exceeded $10,000 a year for more than 150 patients, though health plans disputed some of the findings.

But CMS kept the findings under wraps until the Center for Public Integrity sued the agency under the Freedom of Information Act to make them public.

Despite the alarming results, CMS conducted no audits for payments made during 2008, 2009 and 2010 as they faced industry backlash over CMS’ authority to conduct them, and the threat of extrapolated repayments. Some inside the agency also worried that health plans would abandon the Medicare Advantage program if CMS pressed them too hard, records released through the FOIA lawsuit show.

CMS officials resumed the audits for 2011 and expected to finish them and assess penalties by the end of 2016. That has yet to happen amid the continuing protests from the industry. Insurers want CMS to adjust downward any extrapolated penalties to account for coding errors that exist in standard Medicare. CMS stands behind its method – at least for now.

At a minimum, argues AHIP, the health insurers association, CMS should back off extrapolation for the 90 audits for 2011-13 and apply it for 2014 and onward. Should CMS agree, it would write off more than half a billion dollars that could be recovered for the U.S. Treasury.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Progressive macular hypomelanosis (PMH) presents as asymptomatic, ill-defined hypopigmented macules and patches on the trunk and back. They often coalesce near the midline, and occasionally extend beyond the trunk to the arms, legs, head, or neck. PMH is more frequently diagnosed among black individuals, although it affects all races and ethnicities. The natural history of PMH can vary from stable and progressive disease, and may resolve spontaneously after a few years. The pathogenesis of PMH remains unknown. It has been proposed that the hypopigmentation is caused by decreased melanin production and altered melanosome dispersal in reaction to Propionibacterium acnes.

PMH must be distinguished from some of its clinical mimickers, including vitiligo, hypopigmented mycosis fungoides, tinea versicolor, and pityriasis alba. Potassium hydroxide preparations can be performed in the office to evaluate for tinea versicolor. An additional tool to aid in diagnosis is the use of a Wood’s light. The lesions of PMH characteristically show punctiform orange-red follicular fluorescence when exposed to a Wood’s light, indicating the presence of a porphyrin-producing organism, presumably P. acnes. A skin biopsy is necessary to rule out hypopigmented mycosis fungoides.

Skin biopsy of PMH typically reveals decreased melanin with a normal number of melanocytes. In our patient, a punch biopsy of the right lateral arm demonstrated minimally decreased density of epidermal melanocytes with dermal pigment incontinence. SOX10 immunohistochemical staining demonstrated scattered melanocytes in the epidermis. Preserved melanin within keratinocytes was noted.

In our patient, there was significant spread to the face, which is highly unusual and has only been documented in a few case series. There are no standard recommendations for definitive treatment of PMH. Topical antimicrobial therapies, such as clindamycin solution and benzoyl peroxide gel, have been beneficial in some studies. Tetracyclines, narrow-band ultraviolet B phototherapy, and even isotretinoin have had some reported success.

This case and photo were submitted by Mr. Franzetti, Dr. Rush, and Dr. Shalin of the University of Arkansas for Medical Sciences, Little Rock.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Progressive macular hypomelanosis (PMH) presents as asymptomatic, ill-defined hypopigmented macules and patches on the trunk and back. They often coalesce near the midline, and occasionally extend beyond the trunk to the arms, legs, head, or neck. PMH is more frequently diagnosed among black individuals, although it affects all races and ethnicities. The natural history of PMH can vary from stable and progressive disease, and may resolve spontaneously after a few years. The pathogenesis of PMH remains unknown. It has been proposed that the hypopigmentation is caused by decreased melanin production and altered melanosome dispersal in reaction to Propionibacterium acnes.

PMH must be distinguished from some of its clinical mimickers, including vitiligo, hypopigmented mycosis fungoides, tinea versicolor, and pityriasis alba. Potassium hydroxide preparations can be performed in the office to evaluate for tinea versicolor. An additional tool to aid in diagnosis is the use of a Wood’s light. The lesions of PMH characteristically show punctiform orange-red follicular fluorescence when exposed to a Wood’s light, indicating the presence of a porphyrin-producing organism, presumably P. acnes. A skin biopsy is necessary to rule out hypopigmented mycosis fungoides.

Skin biopsy of PMH typically reveals decreased melanin with a normal number of melanocytes. In our patient, a punch biopsy of the right lateral arm demonstrated minimally decreased density of epidermal melanocytes with dermal pigment incontinence. SOX10 immunohistochemical staining demonstrated scattered melanocytes in the epidermis. Preserved melanin within keratinocytes was noted.

In our patient, there was significant spread to the face, which is highly unusual and has only been documented in a few case series. There are no standard recommendations for definitive treatment of PMH. Topical antimicrobial therapies, such as clindamycin solution and benzoyl peroxide gel, have been beneficial in some studies. Tetracyclines, narrow-band ultraviolet B phototherapy, and even isotretinoin have had some reported success.

This case and photo were submitted by Mr. Franzetti, Dr. Rush, and Dr. Shalin of the University of Arkansas for Medical Sciences, Little Rock.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Progressive macular hypomelanosis (PMH) presents as asymptomatic, ill-defined hypopigmented macules and patches on the trunk and back. They often coalesce near the midline, and occasionally extend beyond the trunk to the arms, legs, head, or neck. PMH is more frequently diagnosed among black individuals, although it affects all races and ethnicities. The natural history of PMH can vary from stable and progressive disease, and may resolve spontaneously after a few years. The pathogenesis of PMH remains unknown. It has been proposed that the hypopigmentation is caused by decreased melanin production and altered melanosome dispersal in reaction to Propionibacterium acnes.

PMH must be distinguished from some of its clinical mimickers, including vitiligo, hypopigmented mycosis fungoides, tinea versicolor, and pityriasis alba. Potassium hydroxide preparations can be performed in the office to evaluate for tinea versicolor. An additional tool to aid in diagnosis is the use of a Wood’s light. The lesions of PMH characteristically show punctiform orange-red follicular fluorescence when exposed to a Wood’s light, indicating the presence of a porphyrin-producing organism, presumably P. acnes. A skin biopsy is necessary to rule out hypopigmented mycosis fungoides.

Skin biopsy of PMH typically reveals decreased melanin with a normal number of melanocytes. In our patient, a punch biopsy of the right lateral arm demonstrated minimally decreased density of epidermal melanocytes with dermal pigment incontinence. SOX10 immunohistochemical staining demonstrated scattered melanocytes in the epidermis. Preserved melanin within keratinocytes was noted.

In our patient, there was significant spread to the face, which is highly unusual and has only been documented in a few case series. There are no standard recommendations for definitive treatment of PMH. Topical antimicrobial therapies, such as clindamycin solution and benzoyl peroxide gel, have been beneficial in some studies. Tetracyclines, narrow-band ultraviolet B phototherapy, and even isotretinoin have had some reported success.

This case and photo were submitted by Mr. Franzetti, Dr. Rush, and Dr. Shalin of the University of Arkansas for Medical Sciences, Little Rock.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].