IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
 

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
 

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
 

The physical and mental health needs of the people of Puerto Rico cannot be underestimated. Just think of what they have been through over the last few months.

When Hurricane Maria barreled onto the island on Sept. 20, 2017 – just 2 weeks after Hurricane Irma reportedly left more than 1 million residents without power – it ripped off roofs and left behind massive flooding, roads washed out, and utility poles and transmission lines knocked down. Whole forests were defoliated, a massive loss of flora and fauna occurred, and 80% of the crop value was destroyed, along with massive loss of stray dogs and cats, dairy cows, industrial chicken coops, and tropical birds, including endangered species. Beloved pets were displaced.

Courtesy Dr. Milner

What we did

ICPT and GFR were a combined team, but we served different functions. As part of ICPT, I focused on the mental health component and helped to train doctors, psychologists, social workers, and other mental health workers in both San Juan and Ponce. All told, we worked with about 50 people using the model of “Training the Trainers.” Many of our students were participants in the outreach teams. Our hope is that they will be able to train their peers to recognize and alleviate symptoms of acute and chronic stress disorders. Some of the techniques taught include patient education, relaxation training, breath work, visualization techniques, mindfulness training, narrative therapy, art therapy, and other expressive techniques.

What the PMSF did

Before Maria, the Ponce Medical School Foundation was in the process of facilitating the transfer of medical records into an electronic format. After the hurricane hit, however, PMSF’s program director, Antonio Fernandez, led a shift to disaster recovery work. PMSF got involved in airlifting dialysis patients off the island to safety, provided health care, and also collaborated with the Primary Care Psychology Program at Ponce Health Services University to assist in locating patients, identifying their health needs – including mental health – and providing for those needs to the extent possible.

At the time of our visit, Puerto Rico’s network of more than 90 largely rural federally funded primary care clinics mostly had reopened, but nearly half remained on back-up generators. Even with the medical centers open, patients were not coming in for one reason or another. People had medical problems, but the daily reality of survival, obtaining food and water, took precedence. Some patients were not showing up because they had left the country, or they were in shelters without transportation. Some people did not have fuel. Some could not keep track of their appointments without cell phones and electricity allowing them to access electronic planners. Some, having been without their medications since the storms, were too sick to travel. Outreach teams were necessary to locate patients, identify their needs, and provide medical and psychological care.
 

Community outreach

Nydia M. Cappas, PsyD, director of the Primary Care Psychology Program, told us that the outreach teams – consisting of doctors or other medical professionals, social workers, and psychologists, were being sent out to communities once a week. They visited homes for the elderly, orphans’ homes, and children in foster care, as well as individual patients. A similar service was provided by Vargas Medicine (VARMED) in the San Juan area.

Team members found that many people were suffering symptoms of posttraumatic stress disorder, even people who did not have prior psychiatric symptoms. They were having flashbacks and nightmares. Those flashbacks and nightmares were being triggered by clouds, by rain, by supplies beginning to run out.

Puerto Rico’s future

Two and a half months after Maria, we learned from our students that things gradually had begun to improve. For example, the public schools had just reopened, and that change was expected to have a stabilizing effect on the children. We also learned that, of the 80 shelters that had been set up housing about 12,500 people, 40 shelters had closed. The five medical shelters that had been set up and funded by FEMA also were in the process of closing, and private donations were beginning to slow down. People were slowly returning to their tarped or otherwise repaired homes, albeit all too often without power.

During the storm, nearly 500,000* homes were destroyed. FEMA offered to airlift about 3,000 people who had no home 2 months past Maria to the U.S. mainland – either Florida or New York.

According to our students, people living in the mountains, mainly coffee growers and retired people and comprising about one-third of the population, remain in acute crisis. Part of the challenge is being able to reach this population: Some roads are still impassable, and supplies – such as drinking water – can be delivered only by helicopter. Despite current conditions, FEMA reportedly has announced that it would end emergency operations on the island.

Our team is currently involved in applying for grant funding that will enable us to return to provide additional training to physicians’ and teachers’ groups. Over the course of the next year, we would like to make six trips to Puerto Rico and focus each trip on a different region and different group of professionals so that the entire island has resources. In addition, we will offer follow-up consultations to professionals we trained previously. The regions to be trained would be San Juan, Ponce, Utuado, Mayagüez, Guayama, and a sixth to be determined upon need. We also would like to address the needs of any ongoing relief workers so that they will be more effective in their ongoing role. Meanwhile, financial assistance from the mainland remains uneven.

Many months after Maria (and Irma), the physical and mental health needs of the Puerto Rican people remain great. However, as mental health professionals, we have the tools to help them move forward.
 

Judith R. Milner, MD, MEd, SpecEd, is a general, child, and adolescent psychiatrist in private practice in Everett, Wash. She has traveled with various groups over the years in an effort to alleviate some of the suffering caused by war and natural disaster. Her predominant association has been with the International Center for Psychosocial Trauma. She also has worked with Step Up Rwanda Women and Pygmy Survival Alliance, as well as on the Committee for Women at the American Psychiatric Association and the Consumer Issues Committee and Membership Committee for the American Academy of Child and Adolescent Psychiatry.

*Correction, 2/12/2018: An earlier version of this story misstated the number of homes reportedly destroyed by Hurricane Maria.

The physical and mental health needs of the people of Puerto Rico cannot be underestimated. Just think of what they have been through over the last few months.

When Hurricane Maria barreled onto the island on Sept. 20, 2017 – just 2 weeks after Hurricane Irma reportedly left more than 1 million residents without power – it ripped off roofs and left behind massive flooding, roads washed out, and utility poles and transmission lines knocked down. Whole forests were defoliated, a massive loss of flora and fauna occurred, and 80% of the crop value was destroyed, along with massive loss of stray dogs and cats, dairy cows, industrial chicken coops, and tropical birds, including endangered species. Beloved pets were displaced.

Courtesy Dr. Milner

What we did

ICPT and GFR were a combined team, but we served different functions. As part of ICPT, I focused on the mental health component and helped to train doctors, psychologists, social workers, and other mental health workers in both San Juan and Ponce. All told, we worked with about 50 people using the model of “Training the Trainers.” Many of our students were participants in the outreach teams. Our hope is that they will be able to train their peers to recognize and alleviate symptoms of acute and chronic stress disorders. Some of the techniques taught include patient education, relaxation training, breath work, visualization techniques, mindfulness training, narrative therapy, art therapy, and other expressive techniques.

What the PMSF did

Before Maria, the Ponce Medical School Foundation was in the process of facilitating the transfer of medical records into an electronic format. After the hurricane hit, however, PMSF’s program director, Antonio Fernandez, led a shift to disaster recovery work. PMSF got involved in airlifting dialysis patients off the island to safety, provided health care, and also collaborated with the Primary Care Psychology Program at Ponce Health Services University to assist in locating patients, identifying their health needs – including mental health – and providing for those needs to the extent possible.

At the time of our visit, Puerto Rico’s network of more than 90 largely rural federally funded primary care clinics mostly had reopened, but nearly half remained on back-up generators. Even with the medical centers open, patients were not coming in for one reason or another. People had medical problems, but the daily reality of survival, obtaining food and water, took precedence. Some patients were not showing up because they had left the country, or they were in shelters without transportation. Some people did not have fuel. Some could not keep track of their appointments without cell phones and electricity allowing them to access electronic planners. Some, having been without their medications since the storms, were too sick to travel. Outreach teams were necessary to locate patients, identify their needs, and provide medical and psychological care.
 

Community outreach

Nydia M. Cappas, PsyD, director of the Primary Care Psychology Program, told us that the outreach teams – consisting of doctors or other medical professionals, social workers, and psychologists, were being sent out to communities once a week. They visited homes for the elderly, orphans’ homes, and children in foster care, as well as individual patients. A similar service was provided by Vargas Medicine (VARMED) in the San Juan area.

Team members found that many people were suffering symptoms of posttraumatic stress disorder, even people who did not have prior psychiatric symptoms. They were having flashbacks and nightmares. Those flashbacks and nightmares were being triggered by clouds, by rain, by supplies beginning to run out.

Puerto Rico’s future

Two and a half months after Maria, we learned from our students that things gradually had begun to improve. For example, the public schools had just reopened, and that change was expected to have a stabilizing effect on the children. We also learned that, of the 80 shelters that had been set up housing about 12,500 people, 40 shelters had closed. The five medical shelters that had been set up and funded by FEMA also were in the process of closing, and private donations were beginning to slow down. People were slowly returning to their tarped or otherwise repaired homes, albeit all too often without power.

During the storm, nearly 500,000* homes were destroyed. FEMA offered to airlift about 3,000 people who had no home 2 months past Maria to the U.S. mainland – either Florida or New York.

According to our students, people living in the mountains, mainly coffee growers and retired people and comprising about one-third of the population, remain in acute crisis. Part of the challenge is being able to reach this population: Some roads are still impassable, and supplies – such as drinking water – can be delivered only by helicopter. Despite current conditions, FEMA reportedly has announced that it would end emergency operations on the island.

Our team is currently involved in applying for grant funding that will enable us to return to provide additional training to physicians’ and teachers’ groups. Over the course of the next year, we would like to make six trips to Puerto Rico and focus each trip on a different region and different group of professionals so that the entire island has resources. In addition, we will offer follow-up consultations to professionals we trained previously. The regions to be trained would be San Juan, Ponce, Utuado, Mayagüez, Guayama, and a sixth to be determined upon need. We also would like to address the needs of any ongoing relief workers so that they will be more effective in their ongoing role. Meanwhile, financial assistance from the mainland remains uneven.

Many months after Maria (and Irma), the physical and mental health needs of the Puerto Rican people remain great. However, as mental health professionals, we have the tools to help them move forward.
 

Judith R. Milner, MD, MEd, SpecEd, is a general, child, and adolescent psychiatrist in private practice in Everett, Wash. She has traveled with various groups over the years in an effort to alleviate some of the suffering caused by war and natural disaster. Her predominant association has been with the International Center for Psychosocial Trauma. She also has worked with Step Up Rwanda Women and Pygmy Survival Alliance, as well as on the Committee for Women at the American Psychiatric Association and the Consumer Issues Committee and Membership Committee for the American Academy of Child and Adolescent Psychiatry.

*Correction, 2/12/2018: An earlier version of this story misstated the number of homes reportedly destroyed by Hurricane Maria.

The physical and mental health needs of the people of Puerto Rico cannot be underestimated. Just think of what they have been through over the last few months.

When Hurricane Maria barreled onto the island on Sept. 20, 2017 – just 2 weeks after Hurricane Irma reportedly left more than 1 million residents without power – it ripped off roofs and left behind massive flooding, roads washed out, and utility poles and transmission lines knocked down. Whole forests were defoliated, a massive loss of flora and fauna occurred, and 80% of the crop value was destroyed, along with massive loss of stray dogs and cats, dairy cows, industrial chicken coops, and tropical birds, including endangered species. Beloved pets were displaced.

Courtesy Dr. Milner

What we did

ICPT and GFR were a combined team, but we served different functions. As part of ICPT, I focused on the mental health component and helped to train doctors, psychologists, social workers, and other mental health workers in both San Juan and Ponce. All told, we worked with about 50 people using the model of “Training the Trainers.” Many of our students were participants in the outreach teams. Our hope is that they will be able to train their peers to recognize and alleviate symptoms of acute and chronic stress disorders. Some of the techniques taught include patient education, relaxation training, breath work, visualization techniques, mindfulness training, narrative therapy, art therapy, and other expressive techniques.

What the PMSF did

Before Maria, the Ponce Medical School Foundation was in the process of facilitating the transfer of medical records into an electronic format. After the hurricane hit, however, PMSF’s program director, Antonio Fernandez, led a shift to disaster recovery work. PMSF got involved in airlifting dialysis patients off the island to safety, provided health care, and also collaborated with the Primary Care Psychology Program at Ponce Health Services University to assist in locating patients, identifying their health needs – including mental health – and providing for those needs to the extent possible.

At the time of our visit, Puerto Rico’s network of more than 90 largely rural federally funded primary care clinics mostly had reopened, but nearly half remained on back-up generators. Even with the medical centers open, patients were not coming in for one reason or another. People had medical problems, but the daily reality of survival, obtaining food and water, took precedence. Some patients were not showing up because they had left the country, or they were in shelters without transportation. Some people did not have fuel. Some could not keep track of their appointments without cell phones and electricity allowing them to access electronic planners. Some, having been without their medications since the storms, were too sick to travel. Outreach teams were necessary to locate patients, identify their needs, and provide medical and psychological care.
 

Community outreach

Nydia M. Cappas, PsyD, director of the Primary Care Psychology Program, told us that the outreach teams – consisting of doctors or other medical professionals, social workers, and psychologists, were being sent out to communities once a week. They visited homes for the elderly, orphans’ homes, and children in foster care, as well as individual patients. A similar service was provided by Vargas Medicine (VARMED) in the San Juan area.

Team members found that many people were suffering symptoms of posttraumatic stress disorder, even people who did not have prior psychiatric symptoms. They were having flashbacks and nightmares. Those flashbacks and nightmares were being triggered by clouds, by rain, by supplies beginning to run out.

Puerto Rico’s future

Two and a half months after Maria, we learned from our students that things gradually had begun to improve. For example, the public schools had just reopened, and that change was expected to have a stabilizing effect on the children. We also learned that, of the 80 shelters that had been set up housing about 12,500 people, 40 shelters had closed. The five medical shelters that had been set up and funded by FEMA also were in the process of closing, and private donations were beginning to slow down. People were slowly returning to their tarped or otherwise repaired homes, albeit all too often without power.

During the storm, nearly 500,000* homes were destroyed. FEMA offered to airlift about 3,000 people who had no home 2 months past Maria to the U.S. mainland – either Florida or New York.

According to our students, people living in the mountains, mainly coffee growers and retired people and comprising about one-third of the population, remain in acute crisis. Part of the challenge is being able to reach this population: Some roads are still impassable, and supplies – such as drinking water – can be delivered only by helicopter. Despite current conditions, FEMA reportedly has announced that it would end emergency operations on the island.

Our team is currently involved in applying for grant funding that will enable us to return to provide additional training to physicians’ and teachers’ groups. Over the course of the next year, we would like to make six trips to Puerto Rico and focus each trip on a different region and different group of professionals so that the entire island has resources. In addition, we will offer follow-up consultations to professionals we trained previously. The regions to be trained would be San Juan, Ponce, Utuado, Mayagüez, Guayama, and a sixth to be determined upon need. We also would like to address the needs of any ongoing relief workers so that they will be more effective in their ongoing role. Meanwhile, financial assistance from the mainland remains uneven.

Many months after Maria (and Irma), the physical and mental health needs of the Puerto Rican people remain great. However, as mental health professionals, we have the tools to help them move forward.
 

Judith R. Milner, MD, MEd, SpecEd, is a general, child, and adolescent psychiatrist in private practice in Everett, Wash. She has traveled with various groups over the years in an effort to alleviate some of the suffering caused by war and natural disaster. Her predominant association has been with the International Center for Psychosocial Trauma. She also has worked with Step Up Rwanda Women and Pygmy Survival Alliance, as well as on the Committee for Women at the American Psychiatric Association and the Consumer Issues Committee and Membership Committee for the American Academy of Child and Adolescent Psychiatry.

*Correction, 2/12/2018: An earlier version of this story misstated the number of homes reportedly destroyed by Hurricane Maria.

Adults with cystic fibrosis (CF) should undergo screening colonoscopy for colorectal cancer every 5 years beginning at age 40 years, unless they have had a solid organ transplant – in which case, screening should begin at age 30 years. For both groups, screening intervals should be shortened to 3 years if any adenomatous polyps are recovered.

The new screening recommendation is 1 of 10 set forth by the Cystic Fibrosis Foundation, in conjunction with the American Gastroenterological Association. The document reflects the significantly increased risk of colorectal cancer among adults with the chronic lung disorder, Denis Hadjiliadis, MD, and his colleagues wrote in the February issue of Gastroenterology. CF patients face up to a 10-fold risk of colorectal cancer, compared with the general population; the risk approaches a 30-fold increase among CF patients who have undergone a lung transplant.

SOURCE: American Gastroenterological Association

In addition to making recommendations on screening intervals and protocols, the document asks clinicians to reframe their thinking of CF as a respiratory-only disease.

“Physicians should recognize that CF is a colon cancer syndrome,” wrote Dr. Hadjiliadis, director of the Adult Cystic Fibrosis Program at the University of Pennsylvania, Philadelphia, and his coauthors.

The increased colorectal cancer risk has become increasingly evident as CF patients live longer, Dr. Hadjiliadis and the panel wrote.

“The current median predicted survival is 41 years, and persons born in 2015 have an estimated average life expectancy of 45 years. The increasing longevity of adults with CF puts them at risk for other diseases, such as gastrointestinal cancer.”

In addition to the normal age-related risk, however, CF patients seem to have an elevated risk profile unique to the disease. The underlying causes have not been fully elucidated but may have to do with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), which are responsible for the excess thickened mucosal secretions that characterize CF. CFTR also is a tumor-suppressor gene in the intestinal tract of mice, and is important in gastrointestinal epithelial homeostasis. “Absence of CFTR is associated with dysregulation of the immune response, intestinal stem cells, and growth signaling regulators,” the authors noted.

In response to this observed increased risk of colorectal cancers among CF patients, the Cystic Fibrosis Foundation convened an 18-member task force to review the extant literature and compile colorectal cancer screening recommendations for CF patients who show no signs of such malignancies. The team reviewed 1,159 articles and based its findings on the 50 most relevant. The papers comprised observational studies, case-control studies, and case reports; there are no randomized clinical trials of screening for this population.

The American Gastroenterological Association reviewed and approved all of the recommendations:

• Screening decisions should be a collaborative process between the CF patient and clinician, taking into account comorbidities, safety, and quality of life. This should include a discussion of expected lifespan; patients with limited lifespan won’t benefit from screening for a slow-growing cancer. Patients should also consider that the colonoscopy prep for CF patients is somewhat more complex than for non-CF patients. “Given these complexities, the task force agreed that individuals with CF and their providers should … carefully assess the risks and benefits of CRC screening and its impact on the health and quality of life for the adult with CF.”
• The decision team should include an endoscopist. An endoscopist with CF training is preferred, but the panel noted these specialists are rare.
• Colonoscopy is the preferred method of screening for CF patients, since it can both detect and remove polyps. “This is one of the main reasons why colonoscopy is the screening procedure of choice for other high-risk groups,” the panel noted.
• There is insufficient evidence to recommend alternate screening methods in CF patients, including CT scanning, colonography, stool-based tests, or flexible sigmoidoscopy.
• In CF patients without signs of CRC, screening should commence at age 40 years and be repeated every 5 years as long as the results are negative.
• Any CF patient who has had adenomatous polyps on a screening colonoscopy should have a repeat colonoscopy within 3 years, unless clinical findings support more frequent screening.
• For any adult CF patient older than age 30 years who has undergone a solid organ transplant, screening colonoscopy should commence within 2 years of transplantation. “Although the absolute risk of CRC in individuals with CF is extremely low for patients younger than 30 years, the risk … greatly increases after lung transplantation,” to 25-30 times the age-adjusted baseline, the panel wrote. “Increased posttransplantation survival means that many transplant patients will enter older age groups where there is an increased risk of cancer.” Screening should be performed after recovery and within 2 years, unless there was a negative colonoscopy in the 5 years before transplant.
• Thereafter, patients who have had a solid organ transplant should undergo colonoscopy every 5 years, based on their life expectancy. “In cases where the expected survival time is limited (less than 10 years), screening should not be performed. For adults appropriately selected, lung transplantation usually increases survival probability. Therefore, a lung transplantation candidate with a short life expectancy is likely to become a screening candidate before and after transplantation at the appropriate ages described here, because the potential survival increases to approximately 10 years.”
• Colonoscopy should be repeated every 3 years on CF patients with transplants with a history of adenomatous polyps. This interval may be as short as 1 year for patients with high-risk, large, or multiple polyps.
• CF patients should undergo more intense bowel prep for colonoscopy, with three-four washes of a minimum of one liter of purgative per wash; the last wash should occur 4-6 hours before the procedure. Split-prep regimens (several smaller-volume washes) are better than a single larger-volume wash. The panel suggested a sample CF-specific regimen available from the Minnesota Cystic Fibrosis Center.

The new document reflects expert consensus on the currently available data, the panel said. As more data emerge, the recommendations might change.

“It is possible that different subpopulations will need more or less frequent schedules for rescreening and surveillance. Our recommendations are making an effort to balance the risk of missing advanced colorectal cancer and minimizing the burden and risk of too frequent examinations.”

None of the panel members had any financial disclosures.

[email protected]

SOURCE: Hadjiliadis D et al. Gastroenterology. 2017 Dec 28. doi. org/10.1053/j.gastro.2017.12.012

Adults with cystic fibrosis (CF) should undergo screening colonoscopy for colorectal cancer every 5 years beginning at age 40 years, unless they have had a solid organ transplant – in which case, screening should begin at age 30 years. For both groups, screening intervals should be shortened to 3 years if any adenomatous polyps are recovered.

The new screening recommendation is 1 of 10 set forth by the Cystic Fibrosis Foundation, in conjunction with the American Gastroenterological Association. The document reflects the significantly increased risk of colorectal cancer among adults with the chronic lung disorder, Denis Hadjiliadis, MD, and his colleagues wrote in the February issue of Gastroenterology. CF patients face up to a 10-fold risk of colorectal cancer, compared with the general population; the risk approaches a 30-fold increase among CF patients who have undergone a lung transplant.

SOURCE: American Gastroenterological Association

In addition to making recommendations on screening intervals and protocols, the document asks clinicians to reframe their thinking of CF as a respiratory-only disease.

“Physicians should recognize that CF is a colon cancer syndrome,” wrote Dr. Hadjiliadis, director of the Adult Cystic Fibrosis Program at the University of Pennsylvania, Philadelphia, and his coauthors.

The increased colorectal cancer risk has become increasingly evident as CF patients live longer, Dr. Hadjiliadis and the panel wrote.

“The current median predicted survival is 41 years, and persons born in 2015 have an estimated average life expectancy of 45 years. The increasing longevity of adults with CF puts them at risk for other diseases, such as gastrointestinal cancer.”

In addition to the normal age-related risk, however, CF patients seem to have an elevated risk profile unique to the disease. The underlying causes have not been fully elucidated but may have to do with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), which are responsible for the excess thickened mucosal secretions that characterize CF. CFTR also is a tumor-suppressor gene in the intestinal tract of mice, and is important in gastrointestinal epithelial homeostasis. “Absence of CFTR is associated with dysregulation of the immune response, intestinal stem cells, and growth signaling regulators,” the authors noted.

In response to this observed increased risk of colorectal cancers among CF patients, the Cystic Fibrosis Foundation convened an 18-member task force to review the extant literature and compile colorectal cancer screening recommendations for CF patients who show no signs of such malignancies. The team reviewed 1,159 articles and based its findings on the 50 most relevant. The papers comprised observational studies, case-control studies, and case reports; there are no randomized clinical trials of screening for this population.

The American Gastroenterological Association reviewed and approved all of the recommendations:

• Screening decisions should be a collaborative process between the CF patient and clinician, taking into account comorbidities, safety, and quality of life. This should include a discussion of expected lifespan; patients with limited lifespan won’t benefit from screening for a slow-growing cancer. Patients should also consider that the colonoscopy prep for CF patients is somewhat more complex than for non-CF patients. “Given these complexities, the task force agreed that individuals with CF and their providers should … carefully assess the risks and benefits of CRC screening and its impact on the health and quality of life for the adult with CF.”
• The decision team should include an endoscopist. An endoscopist with CF training is preferred, but the panel noted these specialists are rare.
• Colonoscopy is the preferred method of screening for CF patients, since it can both detect and remove polyps. “This is one of the main reasons why colonoscopy is the screening procedure of choice for other high-risk groups,” the panel noted.
• There is insufficient evidence to recommend alternate screening methods in CF patients, including CT scanning, colonography, stool-based tests, or flexible sigmoidoscopy.
• In CF patients without signs of CRC, screening should commence at age 40 years and be repeated every 5 years as long as the results are negative.
• Any CF patient who has had adenomatous polyps on a screening colonoscopy should have a repeat colonoscopy within 3 years, unless clinical findings support more frequent screening.
• For any adult CF patient older than age 30 years who has undergone a solid organ transplant, screening colonoscopy should commence within 2 years of transplantation. “Although the absolute risk of CRC in individuals with CF is extremely low for patients younger than 30 years, the risk … greatly increases after lung transplantation,” to 25-30 times the age-adjusted baseline, the panel wrote. “Increased posttransplantation survival means that many transplant patients will enter older age groups where there is an increased risk of cancer.” Screening should be performed after recovery and within 2 years, unless there was a negative colonoscopy in the 5 years before transplant.
• Thereafter, patients who have had a solid organ transplant should undergo colonoscopy every 5 years, based on their life expectancy. “In cases where the expected survival time is limited (less than 10 years), screening should not be performed. For adults appropriately selected, lung transplantation usually increases survival probability. Therefore, a lung transplantation candidate with a short life expectancy is likely to become a screening candidate before and after transplantation at the appropriate ages described here, because the potential survival increases to approximately 10 years.”
• Colonoscopy should be repeated every 3 years on CF patients with transplants with a history of adenomatous polyps. This interval may be as short as 1 year for patients with high-risk, large, or multiple polyps.
• CF patients should undergo more intense bowel prep for colonoscopy, with three-four washes of a minimum of one liter of purgative per wash; the last wash should occur 4-6 hours before the procedure. Split-prep regimens (several smaller-volume washes) are better than a single larger-volume wash. The panel suggested a sample CF-specific regimen available from the Minnesota Cystic Fibrosis Center.

The new document reflects expert consensus on the currently available data, the panel said. As more data emerge, the recommendations might change.

“It is possible that different subpopulations will need more or less frequent schedules for rescreening and surveillance. Our recommendations are making an effort to balance the risk of missing advanced colorectal cancer and minimizing the burden and risk of too frequent examinations.”

None of the panel members had any financial disclosures.

[email protected]

SOURCE: Hadjiliadis D et al. Gastroenterology. 2017 Dec 28. doi. org/10.1053/j.gastro.2017.12.012

Adults with cystic fibrosis (CF) should undergo screening colonoscopy for colorectal cancer every 5 years beginning at age 40 years, unless they have had a solid organ transplant – in which case, screening should begin at age 30 years. For both groups, screening intervals should be shortened to 3 years if any adenomatous polyps are recovered.

The new screening recommendation is 1 of 10 set forth by the Cystic Fibrosis Foundation, in conjunction with the American Gastroenterological Association. The document reflects the significantly increased risk of colorectal cancer among adults with the chronic lung disorder, Denis Hadjiliadis, MD, and his colleagues wrote in the February issue of Gastroenterology. CF patients face up to a 10-fold risk of colorectal cancer, compared with the general population; the risk approaches a 30-fold increase among CF patients who have undergone a lung transplant.

SOURCE: American Gastroenterological Association

In addition to making recommendations on screening intervals and protocols, the document asks clinicians to reframe their thinking of CF as a respiratory-only disease.

“Physicians should recognize that CF is a colon cancer syndrome,” wrote Dr. Hadjiliadis, director of the Adult Cystic Fibrosis Program at the University of Pennsylvania, Philadelphia, and his coauthors.

The increased colorectal cancer risk has become increasingly evident as CF patients live longer, Dr. Hadjiliadis and the panel wrote.

“The current median predicted survival is 41 years, and persons born in 2015 have an estimated average life expectancy of 45 years. The increasing longevity of adults with CF puts them at risk for other diseases, such as gastrointestinal cancer.”

In addition to the normal age-related risk, however, CF patients seem to have an elevated risk profile unique to the disease. The underlying causes have not been fully elucidated but may have to do with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), which are responsible for the excess thickened mucosal secretions that characterize CF. CFTR also is a tumor-suppressor gene in the intestinal tract of mice, and is important in gastrointestinal epithelial homeostasis. “Absence of CFTR is associated with dysregulation of the immune response, intestinal stem cells, and growth signaling regulators,” the authors noted.

In response to this observed increased risk of colorectal cancers among CF patients, the Cystic Fibrosis Foundation convened an 18-member task force to review the extant literature and compile colorectal cancer screening recommendations for CF patients who show no signs of such malignancies. The team reviewed 1,159 articles and based its findings on the 50 most relevant. The papers comprised observational studies, case-control studies, and case reports; there are no randomized clinical trials of screening for this population.

The American Gastroenterological Association reviewed and approved all of the recommendations:

• Screening decisions should be a collaborative process between the CF patient and clinician, taking into account comorbidities, safety, and quality of life. This should include a discussion of expected lifespan; patients with limited lifespan won’t benefit from screening for a slow-growing cancer. Patients should also consider that the colonoscopy prep for CF patients is somewhat more complex than for non-CF patients. “Given these complexities, the task force agreed that individuals with CF and their providers should … carefully assess the risks and benefits of CRC screening and its impact on the health and quality of life for the adult with CF.”
• The decision team should include an endoscopist. An endoscopist with CF training is preferred, but the panel noted these specialists are rare.
• Colonoscopy is the preferred method of screening for CF patients, since it can both detect and remove polyps. “This is one of the main reasons why colonoscopy is the screening procedure of choice for other high-risk groups,” the panel noted.
• There is insufficient evidence to recommend alternate screening methods in CF patients, including CT scanning, colonography, stool-based tests, or flexible sigmoidoscopy.
• In CF patients without signs of CRC, screening should commence at age 40 years and be repeated every 5 years as long as the results are negative.
• Any CF patient who has had adenomatous polyps on a screening colonoscopy should have a repeat colonoscopy within 3 years, unless clinical findings support more frequent screening.
• For any adult CF patient older than age 30 years who has undergone a solid organ transplant, screening colonoscopy should commence within 2 years of transplantation. “Although the absolute risk of CRC in individuals with CF is extremely low for patients younger than 30 years, the risk … greatly increases after lung transplantation,” to 25-30 times the age-adjusted baseline, the panel wrote. “Increased posttransplantation survival means that many transplant patients will enter older age groups where there is an increased risk of cancer.” Screening should be performed after recovery and within 2 years, unless there was a negative colonoscopy in the 5 years before transplant.
• Thereafter, patients who have had a solid organ transplant should undergo colonoscopy every 5 years, based on their life expectancy. “In cases where the expected survival time is limited (less than 10 years), screening should not be performed. For adults appropriately selected, lung transplantation usually increases survival probability. Therefore, a lung transplantation candidate with a short life expectancy is likely to become a screening candidate before and after transplantation at the appropriate ages described here, because the potential survival increases to approximately 10 years.”
• Colonoscopy should be repeated every 3 years on CF patients with transplants with a history of adenomatous polyps. This interval may be as short as 1 year for patients with high-risk, large, or multiple polyps.
• CF patients should undergo more intense bowel prep for colonoscopy, with three-four washes of a minimum of one liter of purgative per wash; the last wash should occur 4-6 hours before the procedure. Split-prep regimens (several smaller-volume washes) are better than a single larger-volume wash. The panel suggested a sample CF-specific regimen available from the Minnesota Cystic Fibrosis Center.

The new document reflects expert consensus on the currently available data, the panel said. As more data emerge, the recommendations might change.

“It is possible that different subpopulations will need more or less frequent schedules for rescreening and surveillance. Our recommendations are making an effort to balance the risk of missing advanced colorectal cancer and minimizing the burden and risk of too frequent examinations.”

None of the panel members had any financial disclosures.

[email protected]

SOURCE: Hadjiliadis D et al. Gastroenterology. 2017 Dec 28. doi. org/10.1053/j.gastro.2017.12.012

A gluten-free diet was associated with significantly increased blood levels of mercury, lead, and cadmium and with significantly increased urinary levels of arsenic in a large cross-sectional population-based survey study.

Source: American Gastroenterological Association

After researchers controlled for demographic characteristics, “levels of all heavy metals remained significantly higher in persons following a gluten-free diet, compared with those not following a gluten-free diet,” Stephanie L. Raehsler, MPH, of Mayo Clinic in Rochester, Minn., wrote with her associates in an article published in the February issue of Clinical Gastroenterology and Hepatology.

The purported (unproven) benefits of a gluten-free diet (GFD) have propelled them into the mainstream outside the settings of celiac disease, dermatitis herpetiformis, and wheat allergy. However, GFDs have been linked to nutritional deficits of iron, ferritin, zinc, and fiber, to increased consumption of sugar, fats, and salt, and to excessive bioaccumulation of mercury, the investigators noted.

High intake of rice, a staple of many GFDs, also has been associated with elevated urinary excretion of arsenic (PLoS One. 2014 Sep 8;9[9]:e104768. doi: 10.1371/journal.pone.0104768). To further characterize these relationships, the researchers analyzed data for 2009 through 2012 from 11,354 participants in the National Health and Nutrition Examination Survey (NHANES). Blood levels of lead, mercury, and cadmium were available from 115 participants who reported following a GFD, and data on urinary arsenic levels were available from 32 such individuals.

In the overall study group, blood mercury levels averaged 1.37 mcg/L (95% confidence interval, 1.02-1.85 mcg/L) among persons on a GFD and 0.93 mcg/L (95% CI, 0.86-1.0 mcg/L) in persons not on a GFD (P = .008). Individuals on a GFD also had significantly higher total blood levels of lead (1.42 vs. 1.13 mcg/L; P = .007 ) and cadmium (0.42 vs. 0.34; P = .03), and they had significantly higher urinary levels of total arsenic (15.2 vs. 8.4 mcg/L; P = .003). These significant differences persisted after researchers controlled for age, sex, race, and smoking status.

Additionally, among 101 individuals on GFDs who had no laboratory or clinical indication of celiac disease, blood levels of total mercury were significantly elevated, compared with individuals not on a GFD (1.40 vs. 0.93 mcg/L; P = .02), as were blood lead concentrations (1.44 vs. 1.13 mcg/L; P = .01) and urinary arsenic levels (14.7 vs. 8.3 mcg/L; P = .01). Blood cadmium levels also were increased (0.42 vs. 0.34 mcg/L), but this difference did not reach statistical significance (P = .06).

Individuals who reported eating fish or shellfish in the past month had higher blood mercury levels than those who did not, regardless of whether they were on a GFD. However, only two individuals in the study exceeded the toxicity threshold for mercury and neither was on a GFD, the researchers said. For most individuals on a GFD, levels of all heavy metals except urinary arsenic stayed under the recognized limits for toxicity, they noted.

The number of respondents following a GFD was small, but the investigators followed NHANES recommendations on sampling weights and sample design variables. Also, although the NHANES included only one question on GFDs, trained interviewers were used to help minimize bias. “Studies are needed to determine the long-term effects of accumulation of these elements in persons on a GFD,” the researchers concluded.

The Centers for Disease Control and Prevention provided partial funding. The researchers reported having no conflicts of interest.
 

SOURCE: Raehsler S et al. Clin Gastro Hepatol. 2018;(in press).

A gluten-free diet was associated with significantly increased blood levels of mercury, lead, and cadmium and with significantly increased urinary levels of arsenic in a large cross-sectional population-based survey study.

Source: American Gastroenterological Association

After researchers controlled for demographic characteristics, “levels of all heavy metals remained significantly higher in persons following a gluten-free diet, compared with those not following a gluten-free diet,” Stephanie L. Raehsler, MPH, of Mayo Clinic in Rochester, Minn., wrote with her associates in an article published in the February issue of Clinical Gastroenterology and Hepatology.

The purported (unproven) benefits of a gluten-free diet (GFD) have propelled them into the mainstream outside the settings of celiac disease, dermatitis herpetiformis, and wheat allergy. However, GFDs have been linked to nutritional deficits of iron, ferritin, zinc, and fiber, to increased consumption of sugar, fats, and salt, and to excessive bioaccumulation of mercury, the investigators noted.

High intake of rice, a staple of many GFDs, also has been associated with elevated urinary excretion of arsenic (PLoS One. 2014 Sep 8;9[9]:e104768. doi: 10.1371/journal.pone.0104768). To further characterize these relationships, the researchers analyzed data for 2009 through 2012 from 11,354 participants in the National Health and Nutrition Examination Survey (NHANES). Blood levels of lead, mercury, and cadmium were available from 115 participants who reported following a GFD, and data on urinary arsenic levels were available from 32 such individuals.

In the overall study group, blood mercury levels averaged 1.37 mcg/L (95% confidence interval, 1.02-1.85 mcg/L) among persons on a GFD and 0.93 mcg/L (95% CI, 0.86-1.0 mcg/L) in persons not on a GFD (P = .008). Individuals on a GFD also had significantly higher total blood levels of lead (1.42 vs. 1.13 mcg/L; P = .007 ) and cadmium (0.42 vs. 0.34; P = .03), and they had significantly higher urinary levels of total arsenic (15.2 vs. 8.4 mcg/L; P = .003). These significant differences persisted after researchers controlled for age, sex, race, and smoking status.

Additionally, among 101 individuals on GFDs who had no laboratory or clinical indication of celiac disease, blood levels of total mercury were significantly elevated, compared with individuals not on a GFD (1.40 vs. 0.93 mcg/L; P = .02), as were blood lead concentrations (1.44 vs. 1.13 mcg/L; P = .01) and urinary arsenic levels (14.7 vs. 8.3 mcg/L; P = .01). Blood cadmium levels also were increased (0.42 vs. 0.34 mcg/L), but this difference did not reach statistical significance (P = .06).

Individuals who reported eating fish or shellfish in the past month had higher blood mercury levels than those who did not, regardless of whether they were on a GFD. However, only two individuals in the study exceeded the toxicity threshold for mercury and neither was on a GFD, the researchers said. For most individuals on a GFD, levels of all heavy metals except urinary arsenic stayed under the recognized limits for toxicity, they noted.

The number of respondents following a GFD was small, but the investigators followed NHANES recommendations on sampling weights and sample design variables. Also, although the NHANES included only one question on GFDs, trained interviewers were used to help minimize bias. “Studies are needed to determine the long-term effects of accumulation of these elements in persons on a GFD,” the researchers concluded.

The Centers for Disease Control and Prevention provided partial funding. The researchers reported having no conflicts of interest.
 

SOURCE: Raehsler S et al. Clin Gastro Hepatol. 2018;(in press).

A gluten-free diet was associated with significantly increased blood levels of mercury, lead, and cadmium and with significantly increased urinary levels of arsenic in a large cross-sectional population-based survey study.

Source: American Gastroenterological Association

After researchers controlled for demographic characteristics, “levels of all heavy metals remained significantly higher in persons following a gluten-free diet, compared with those not following a gluten-free diet,” Stephanie L. Raehsler, MPH, of Mayo Clinic in Rochester, Minn., wrote with her associates in an article published in the February issue of Clinical Gastroenterology and Hepatology.

The purported (unproven) benefits of a gluten-free diet (GFD) have propelled them into the mainstream outside the settings of celiac disease, dermatitis herpetiformis, and wheat allergy. However, GFDs have been linked to nutritional deficits of iron, ferritin, zinc, and fiber, to increased consumption of sugar, fats, and salt, and to excessive bioaccumulation of mercury, the investigators noted.

High intake of rice, a staple of many GFDs, also has been associated with elevated urinary excretion of arsenic (PLoS One. 2014 Sep 8;9[9]:e104768. doi: 10.1371/journal.pone.0104768). To further characterize these relationships, the researchers analyzed data for 2009 through 2012 from 11,354 participants in the National Health and Nutrition Examination Survey (NHANES). Blood levels of lead, mercury, and cadmium were available from 115 participants who reported following a GFD, and data on urinary arsenic levels were available from 32 such individuals.

In the overall study group, blood mercury levels averaged 1.37 mcg/L (95% confidence interval, 1.02-1.85 mcg/L) among persons on a GFD and 0.93 mcg/L (95% CI, 0.86-1.0 mcg/L) in persons not on a GFD (P = .008). Individuals on a GFD also had significantly higher total blood levels of lead (1.42 vs. 1.13 mcg/L; P = .007 ) and cadmium (0.42 vs. 0.34; P = .03), and they had significantly higher urinary levels of total arsenic (15.2 vs. 8.4 mcg/L; P = .003). These significant differences persisted after researchers controlled for age, sex, race, and smoking status.

Additionally, among 101 individuals on GFDs who had no laboratory or clinical indication of celiac disease, blood levels of total mercury were significantly elevated, compared with individuals not on a GFD (1.40 vs. 0.93 mcg/L; P = .02), as were blood lead concentrations (1.44 vs. 1.13 mcg/L; P = .01) and urinary arsenic levels (14.7 vs. 8.3 mcg/L; P = .01). Blood cadmium levels also were increased (0.42 vs. 0.34 mcg/L), but this difference did not reach statistical significance (P = .06).

Individuals who reported eating fish or shellfish in the past month had higher blood mercury levels than those who did not, regardless of whether they were on a GFD. However, only two individuals in the study exceeded the toxicity threshold for mercury and neither was on a GFD, the researchers said. For most individuals on a GFD, levels of all heavy metals except urinary arsenic stayed under the recognized limits for toxicity, they noted.

The number of respondents following a GFD was small, but the investigators followed NHANES recommendations on sampling weights and sample design variables. Also, although the NHANES included only one question on GFDs, trained interviewers were used to help minimize bias. “Studies are needed to determine the long-term effects of accumulation of these elements in persons on a GFD,” the researchers concluded.

The Centers for Disease Control and Prevention provided partial funding. The researchers reported having no conflicts of interest.
 

SOURCE: Raehsler S et al. Clin Gastro Hepatol. 2018;(in press).

The ability of a patient to focus over time is often impaired among children with epilepsy, and intraindividual variability may be an important way to measure such attentional problems according to a study published in Epilepsy & Behavior.

• Intraindividual variability, a measure of changes in an individual’s transient behavioral performance, has been identified in both pediatric and adult patients with epilepsy.
• Srnka et al evaluated intraindividual variability in 144 patients who had just been diagnosed with epilepsy, using the Connors Continuous Performance Task-II as a metric.
• The children with epilepsy were between the ages of 8 and 18 years and were compared to 82 healthy children.
• The researchers found a large difference in variability between the two groups, with an effect size difference of 0.68.
• They also discovered that intraindividual variability predicted intellectual functioning and academic achievement.

Srnka K, Seidenberg M, Hermann B, Jones J. Intraindividual variability in attentional vigilance in children with epilepsy.  Epilepsy Behav. 2018;79:42-45.

The ability of a patient to focus over time is often impaired among children with epilepsy, and intraindividual variability may be an important way to measure such attentional problems according to a study published in Epilepsy & Behavior.

• Intraindividual variability, a measure of changes in an individual’s transient behavioral performance, has been identified in both pediatric and adult patients with epilepsy.
• Srnka et al evaluated intraindividual variability in 144 patients who had just been diagnosed with epilepsy, using the Connors Continuous Performance Task-II as a metric.
• The children with epilepsy were between the ages of 8 and 18 years and were compared to 82 healthy children.
• The researchers found a large difference in variability between the two groups, with an effect size difference of 0.68.
• They also discovered that intraindividual variability predicted intellectual functioning and academic achievement.

Srnka K, Seidenberg M, Hermann B, Jones J. Intraindividual variability in attentional vigilance in children with epilepsy.  Epilepsy Behav. 2018;79:42-45.

The ability of a patient to focus over time is often impaired among children with epilepsy, and intraindividual variability may be an important way to measure such attentional problems according to a study published in Epilepsy & Behavior.

• Intraindividual variability, a measure of changes in an individual’s transient behavioral performance, has been identified in both pediatric and adult patients with epilepsy.
• Srnka et al evaluated intraindividual variability in 144 patients who had just been diagnosed with epilepsy, using the Connors Continuous Performance Task-II as a metric.
• The children with epilepsy were between the ages of 8 and 18 years and were compared to 82 healthy children.
• The researchers found a large difference in variability between the two groups, with an effect size difference of 0.68.
• They also discovered that intraindividual variability predicted intellectual functioning and academic achievement.

Srnka K, Seidenberg M, Hermann B, Jones J. Intraindividual variability in attentional vigilance in children with epilepsy.  Epilepsy Behav. 2018;79:42-45.

Magnetoencephalography (MEG) may play an important role in the presurgical workup of patients with nonlesional refractory focal epilepsy suggests a recent observational study.

• Investigators observed 31 patients at an academic epilepsy center to determine if MEG would have had an impact on patient care; (they were unable to analyze the MEG early enough to influence the decision-making process).
• Had the test been integrated into the presurgical workup, 68% of patients would have received different management initially.
• MEG would have reduced the number of patients who received intracranial electrodes.
• MEG would also have led to the position of the electrodes being changed or provided adequate evidence to justify the use of an intracranial electrode.
• The results of the MEG studies would have let surgeons do direct surgery with no need for intracranial electrodes in 2 of 11 patients.
• 6 patients fared poorly after surgery, but MEG would have changed their outcomes in 3 of these patients by modifying the resection margin.

Mohamed IS, Bout hillier A, Bérubé A, et al. The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy. Epilepsy Behav. 2018;79:34-41.

Magnetoencephalography (MEG) may play an important role in the presurgical workup of patients with nonlesional refractory focal epilepsy suggests a recent observational study.

• Investigators observed 31 patients at an academic epilepsy center to determine if MEG would have had an impact on patient care; (they were unable to analyze the MEG early enough to influence the decision-making process).
• Had the test been integrated into the presurgical workup, 68% of patients would have received different management initially.
• MEG would have reduced the number of patients who received intracranial electrodes.
• MEG would also have led to the position of the electrodes being changed or provided adequate evidence to justify the use of an intracranial electrode.
• The results of the MEG studies would have let surgeons do direct surgery with no need for intracranial electrodes in 2 of 11 patients.
• 6 patients fared poorly after surgery, but MEG would have changed their outcomes in 3 of these patients by modifying the resection margin.

Mohamed IS, Bout hillier A, Bérubé A, et al. The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy. Epilepsy Behav. 2018;79:34-41.

Magnetoencephalography (MEG) may play an important role in the presurgical workup of patients with nonlesional refractory focal epilepsy suggests a recent observational study.

• Investigators observed 31 patients at an academic epilepsy center to determine if MEG would have had an impact on patient care; (they were unable to analyze the MEG early enough to influence the decision-making process).
• Had the test been integrated into the presurgical workup, 68% of patients would have received different management initially.
• MEG would have reduced the number of patients who received intracranial electrodes.
• MEG would also have led to the position of the electrodes being changed or provided adequate evidence to justify the use of an intracranial electrode.
• The results of the MEG studies would have let surgeons do direct surgery with no need for intracranial electrodes in 2 of 11 patients.
• 6 patients fared poorly after surgery, but MEG would have changed their outcomes in 3 of these patients by modifying the resection margin.

Mohamed IS, Bout hillier A, Bérubé A, et al. The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy. Epilepsy Behav. 2018;79:34-41.

Electrocorticographic (ECoG) high-γ modulation (HGM) can serve as a specific way to localize language preoperatively, when compared with electrical stimulation mapping (ESM), which is considered the gold standard, according to a recent meta-analysis. But the same analysis concluded that it was not sensitive enough when compared with ESM.

• The meta-analysis reviewed several metrics for diagnostic validity, including area under the summary receiver operating characteristic (SROC) curve, diagnostic odds ratio, and pooled estimates of sensitivity and specificity.
• To determine language mapping, the most common task used was overt picture naming.
• ECoG was analyzed at 50 to 400 Hz, with different studies using different bandwidths.
• Among the studies that looked at ESM, there were wide variations in pulse duration, train duration, and maximum current.
• The pooled diagnostic odds ratio was 6.44 and the AUC was 0.77, making HGM a fairly reliable way to ascertain electrodes overlying ESM cortical language sites.

Aryaa R, Horn PS, Crone NE, et al. ECoG high-gamma modulation versus electrical stimulation for presurgical language mapping. Epilepsy Behav. 2018;79:26-33.

Electrocorticographic (ECoG) high-γ modulation (HGM) can serve as a specific way to localize language preoperatively, when compared with electrical stimulation mapping (ESM), which is considered the gold standard, according to a recent meta-analysis. But the same analysis concluded that it was not sensitive enough when compared with ESM.

• The meta-analysis reviewed several metrics for diagnostic validity, including area under the summary receiver operating characteristic (SROC) curve, diagnostic odds ratio, and pooled estimates of sensitivity and specificity.
• To determine language mapping, the most common task used was overt picture naming.
• ECoG was analyzed at 50 to 400 Hz, with different studies using different bandwidths.
• Among the studies that looked at ESM, there were wide variations in pulse duration, train duration, and maximum current.
• The pooled diagnostic odds ratio was 6.44 and the AUC was 0.77, making HGM a fairly reliable way to ascertain electrodes overlying ESM cortical language sites.

Aryaa R, Horn PS, Crone NE, et al. ECoG high-gamma modulation versus electrical stimulation for presurgical language mapping. Epilepsy Behav. 2018;79:26-33.

Electrocorticographic (ECoG) high-γ modulation (HGM) can serve as a specific way to localize language preoperatively, when compared with electrical stimulation mapping (ESM), which is considered the gold standard, according to a recent meta-analysis. But the same analysis concluded that it was not sensitive enough when compared with ESM.

• The meta-analysis reviewed several metrics for diagnostic validity, including area under the summary receiver operating characteristic (SROC) curve, diagnostic odds ratio, and pooled estimates of sensitivity and specificity.
• To determine language mapping, the most common task used was overt picture naming.
• ECoG was analyzed at 50 to 400 Hz, with different studies using different bandwidths.
• Among the studies that looked at ESM, there were wide variations in pulse duration, train duration, and maximum current.
• The pooled diagnostic odds ratio was 6.44 and the AUC was 0.77, making HGM a fairly reliable way to ascertain electrodes overlying ESM cortical language sites.

Aryaa R, Horn PS, Crone NE, et al. ECoG high-gamma modulation versus electrical stimulation for presurgical language mapping. Epilepsy Behav. 2018;79:26-33.

Transcranial Magnetic Stimulation Improves Memory in Older Adults

A painless and noninvasive brain stimulation technique may help improve some types of memory in older adults, investigators reported.

One possible explanation for age-related memory loss is degradation of the neural connections between the hippocampus and the cortex. Weakening of these connections may lead to difficulties in creating new memories of specific events and the locations of objects. Scientists hypothesized that strengthening the connections between the hippocampus and cortex through repetitive transcranial magnetic stimulation (TMS) may help the storage of new memories. TMS delivers painless magnetic pulses to a particular region of the brain, changing the activity of the neurons within the targeted area.

To determine whether TMS could improve memory, 15 healthy adults over the age of 64 received TMS to a part of the cortex that communicates with the hippocampus. Treatment lasted for five days. During a separate week, each participant received five days of sham treatment, in which the setup was the same, but the stimulation was too low to influence the neural connections. Before and after each five-day session, participants were asked to remember pictures of everyday objects and pictures of outdoor scenes associated with each one. The adults’ ability to recall the scenes associated with the objects improved after receiving TMS, but not after the sham treatment.

“Our study demonstrates that TMS could potentially be used as a way to improve memory for older adults experiencing age-related memory impairments,” said John A. Walker, PhD, postdoctorate fellow at Northwestern University in Evanston, Illinois. “TMS can be used to probe the relationship between brain networks and memory experimentally, opening new doors to understanding the network basis of cognitive decline in aging.”

Heading the Ball Hurts Women More Than Men

Intentionally hitting a soccer ball with the head, or “heading,” may have more adverse brain consequences for women than men, said researchers.

Heading does not typically result in a concussion, yet growing evidence links the move to CNS damage. Previous studies using diffusion tensor imaging (DTI) have revealed that heading damages the integrity of the axons. Women appear to be more vulnerable than men to problems associated with heading, as they report more symptoms that last longer, but the reason for these gender differences remains unknown.

To assess possible gender differences in the effects of heading, researchers used DTI to examine 49 male and 49 female amateur soccer players who were matched on age and frequency of heading. Higher levels of heading were associated with decreased axonal integrity in three brain regions for men and eight brain regions for women. In seven of the areas identified in women, the association between axonal integrity and heading was significantly stronger than it was in men.

“Given similar amounts of exposure to heading, women show a greater volume of abnormality that is significantly different from what is seen in men,” said lead author Todd G. Rubin, MD, a doctoral student at Albert Einstein College of Medicine in Bronx, New York. “Identifying and understanding the basis for differences in susceptibility to injury represent key steps in determining better treatments and guidelines for safer play.”

DBS Can Individualize Treatment for Parkinson’s Disease

A new approach to deep brain stimulation (DBS) adjusts itself to deliver the appropriate amount of stimulation in patients with Parkinson’s disease, according to new research. The approach could improve symptom management and reduce side effects.

DBS has been a valuable treatment for Parkinson’s disease by helping to quell the abnormal movements that are characteristic of the disease. Traditional DBS delivers a constant level of stimulation and cannot adapt if a patient’s symptoms vary over the course of a day. As a result, a patient may sometimes receive too little stimulation, which fails to control symptoms, or too much, which causes side effects such as dyskinesia.

To match stimulation to variations in patient symptoms throughout the day, researchers and engineers developed a novel implantable device that provides DBS and records activity from the surface of the brain. Similar to a cardiac pacemaker, this adaptive device can autoadjust its level of stimulation based on a physiologic signal—in this case, brain activity related to dyskinesia. A high dyskinesia signal indicated greater likelihood of unwanted side effects and caused the device to reduce the stimulation level. A low signal indicated a higher chance of symptoms returning and triggered an increase in stimulation.

The device was tested in two patients inside and outside of the laboratory. Neither patient reported discomfort, adverse events, or worsening symptoms. In addition, the battery used as much as 45% less energy than traditional DBS, which is an important advantage, since battery replacement requires surgery.

“Our study showed that totally implanted, adaptive DBS is feasible and can be used at home in patients,” said lead author Nicole C. Swann, PhD, Assistant Professor of Human Physiology at the University of Oregon in Eugene. “Adaptive stimulation represents one of the first major advances in DBS technology since this technique was first introduced for the treatment of Parkinson’s disease 25 years ago.”

Contact Sports May Impair Memory Temporarily

Sports-related head injuries may prevent the generation of new neurons in a brain region important for memory, said investigators.

Concussion can lead to cognitive impairments, and recent evidence indicates that subconcussive hits can cause damage. The hippocampus is particularly vulnerable. One way to test the effects of head impacts on the hippocampus is a memory assessment called the mnemonic similarity test (MST), which evaluates a person’s ability to distinguish between images that are novel, previously presented, or similar to images previously presented. Accumulating evidence suggests that MST scores are related to the hippocampus’s ability to generate new neurons.

To investigate changes in memory following sports-related head injuries, researchers assessed different types of athletes in two studies. In the first study, they compared athletes with concussion, uninjured athletes who played the same sport, same-sport athletes with musculoskeletal injuries, and healthy controls. Compared with the other three groups, concussed athletes performed worse on the MST when tested two to four weeks after their injury. The scores did not remain low, however. By the time the athletes were cleared to play, their scores had improved to normal levels.

In the second study, rugby players were given the MST before the season started, halfway through the season, and one month after their last game. Scores dropped midseason, compared with preseason scores, but recovered by the postseason assessment.

“Using a cognitive test believed to be sensitive to hippocampal neurogenesis, we found that athletes with concussion show impairments that resolve following recovery,” said lead author Melissa Danielle McCradden, PhD, a postdoctoral fellow at McMaster University in Toronto. “These findings represent, to the best of our knowledge, the first reported evidence in humans suggesting a brain change that might explain the cognitive and emotional symptoms associated with mild traumatic brain injury.”

Disrupted Brain Networks May Cause Gulf War Illness

The brains of veterans with Gulf War illness (GWI) show widespread communication abnormalities in networks that support various brain functions, researchers reported. The observed patterns of impairment provide objective neurophysiologic evidence to support the self-reported symptoms of veterans with GWI.

As many as 250,000 veterans who served in Iraq, Kuwait, and Saudi Arabia during the 1991 Gulf War may currently experience GWI. Symptoms include difficulty remembering things, trouble finding words while speaking, motor coordination, mood swings, fatigue, and chronic pain. GWI is thought to result from exposure to a mix of chemical and biological warfare agents and hazardous chemicals.

To better understand brain changes in GWI, researchers compared the brains of 22 veterans with GWI to the brains of 30 healthy veterans of similar age. Using resting state functional MRI, researchers analyzed patterns of communication among regions of the brain known to control different functions and behavior. They identified changes in functional networks related to many commonly reported GWI symptoms. Individuals with GWI showed clear deficits in neural communication in the sectors of the brain responsible for visual processing, mood regulation, motor coordination, sensory processing, and language command, but increased communication in networks related to pain perception during rest.

“The results from this study provide strong evidence of neuropathology in GWI patients from exposures to neurotoxic agents,” said lead author Kaundinya Gopinath, PhD, Assistant Professor of Radiology and Imaging Sciences at Emory University in Atlanta. Next, “the aim is to establish brain mechanisms underlying GWI, which in turn can lead to development of treatments.”

Prolonged Sedation May Cause Brain Abnormalities in Infants

Full-term infants who undergo repeated anesthesia and prolonged sedation are at risk for changes in brain development, according to investigators.

Developmental impacts of prenatal exposure to sedatives have been studied widely, but less is known about the immediate and long-term neurologic and developmental effects of prolonged sedation when administered to critically ill infants after birth. Prolonged administration of opioids and benzodiazepines, which commonly are used for infants undergoing surgery, is associated with a high incidence of drug tolerance and dependence. Although negative long-term outcomes have been associated with such drug exposures in infants, these studies could not exclude other possible causes, such as prematurity or heart problems.

To study neurologic effects of prolonged sedation, researchers conducted MRI scans on full-term infants who underwent life-saving surgery that required prolonged exposure to morphine and midazolam before one year of age. Brain imaging showed several brain MRI anomalies that were not present in healthy infants, including abnormalities in gray and white matter structures and the ventricles. The number of brain MRI abnormalities significantly correlated with the average daily dose of these sedative drugs. The higher the daily dose, the more MRI irregularities were seen. The patients also had more brain fluid and a smaller total brain volume, compared with healthy infants. This pattern has been associated with long-term neurodevelopmental outcomes such as autism spectrum disorder. Taken together, these preliminary findings indicate a potential negative impact of prolonged sedation on brain growth during the first year of life, the researchers said.

“We were surprised to find higher incidence of brain abnormalities in full-term infants who underwent life-saving surgery that required prolonged sedation,” said senior author Dusica Bajic, MD, PhD, Principal Investigator at Boston Children’s Hospital. “The constellation of MRI irregularities suggests prolonged sedation may potentially contribute to delayed brain growth.” Future investigations will explore the neural mechanisms of the observed developmental effects and whether early sedation exposure may lead to long-term neurobehavioral impacts.

The Brain Preferentially Reactivates Negative Memories During Sleep

The brain selectively reactivates negative memories during sleep, prioritizing the retention of these emotional memories, which may be of greater future relevance than neutral memories and thus more worth remembering, according to investigators.

Over the past two decades, neuroscientists have gained increased understanding of how sleep boosts and stabilizes memories in the human brain. In the current study, researchers presented 57 healthy volunteers with a series of neutral and negative images. While staring straight ahead, the volunteers saw all of the negative images on one side of their field of vision (left) and all of the neutral images on the other side (right). Because the brain processes visual information in the opposite hemisphere from where it is viewed, this method allowed researchers to “tag” one hemisphere with negative content and the other with neutral content, thus enabling them to track localized memories. Participants were then shown the previously seen images for memory tests, with some of the images shown immediately after the learning phase and the rest shown after a period of wakefulness or sleep. During all memory tests, volunteers viewed the images directly in front of them, rather than to either side, and researchers asked participants to state whether an image had originally appeared to the left or right.

Participants who stayed awake in between memory tests forgot some of the original image locations, but forgetting was similar for neutral and negative images. Participants who slept between tests, on the other hand, had a much better rate of recall for the negative images than for the neutral ones. EEG recordings made during the learning phase show that the brain has encoded the distinct types of memories in its two hemispheres, with the negative images strongly encoded in the hemisphere opposite to the side of presentation. Researchers are now analyzing data that they hypothesize will show that the waking EEG pattern corresponding to emotional memories is the same pattern that is reactivated most strongly during sleep.

“This [finding] would provide a long sought-after brain-based explanation of how sleep selectively stabilizes emotional memories,” said lead author Roy Cox, PhD, research fellow in psychiatry at Beth Israel Deaconess Medical Center in Boston. “Our research substantially advances the notion that sleep plays a fundamental and complex role in the offline reorganization of waking experiences.”

Transcranial Magnetic Stimulation Improves Memory in Older Adults

A painless and noninvasive brain stimulation technique may help improve some types of memory in older adults, investigators reported.

One possible explanation for age-related memory loss is degradation of the neural connections between the hippocampus and the cortex. Weakening of these connections may lead to difficulties in creating new memories of specific events and the locations of objects. Scientists hypothesized that strengthening the connections between the hippocampus and cortex through repetitive transcranial magnetic stimulation (TMS) may help the storage of new memories. TMS delivers painless magnetic pulses to a particular region of the brain, changing the activity of the neurons within the targeted area.

To determine whether TMS could improve memory, 15 healthy adults over the age of 64 received TMS to a part of the cortex that communicates with the hippocampus. Treatment lasted for five days. During a separate week, each participant received five days of sham treatment, in which the setup was the same, but the stimulation was too low to influence the neural connections. Before and after each five-day session, participants were asked to remember pictures of everyday objects and pictures of outdoor scenes associated with each one. The adults’ ability to recall the scenes associated with the objects improved after receiving TMS, but not after the sham treatment.

“Our study demonstrates that TMS could potentially be used as a way to improve memory for older adults experiencing age-related memory impairments,” said John A. Walker, PhD, postdoctorate fellow at Northwestern University in Evanston, Illinois. “TMS can be used to probe the relationship between brain networks and memory experimentally, opening new doors to understanding the network basis of cognitive decline in aging.”

Heading the Ball Hurts Women More Than Men

Intentionally hitting a soccer ball with the head, or “heading,” may have more adverse brain consequences for women than men, said researchers.

Heading does not typically result in a concussion, yet growing evidence links the move to CNS damage. Previous studies using diffusion tensor imaging (DTI) have revealed that heading damages the integrity of the axons. Women appear to be more vulnerable than men to problems associated with heading, as they report more symptoms that last longer, but the reason for these gender differences remains unknown.

To assess possible gender differences in the effects of heading, researchers used DTI to examine 49 male and 49 female amateur soccer players who were matched on age and frequency of heading. Higher levels of heading were associated with decreased axonal integrity in three brain regions for men and eight brain regions for women. In seven of the areas identified in women, the association between axonal integrity and heading was significantly stronger than it was in men.

“Given similar amounts of exposure to heading, women show a greater volume of abnormality that is significantly different from what is seen in men,” said lead author Todd G. Rubin, MD, a doctoral student at Albert Einstein College of Medicine in Bronx, New York. “Identifying and understanding the basis for differences in susceptibility to injury represent key steps in determining better treatments and guidelines for safer play.”

DBS Can Individualize Treatment for Parkinson’s Disease

A new approach to deep brain stimulation (DBS) adjusts itself to deliver the appropriate amount of stimulation in patients with Parkinson’s disease, according to new research. The approach could improve symptom management and reduce side effects.

DBS has been a valuable treatment for Parkinson’s disease by helping to quell the abnormal movements that are characteristic of the disease. Traditional DBS delivers a constant level of stimulation and cannot adapt if a patient’s symptoms vary over the course of a day. As a result, a patient may sometimes receive too little stimulation, which fails to control symptoms, or too much, which causes side effects such as dyskinesia.

To match stimulation to variations in patient symptoms throughout the day, researchers and engineers developed a novel implantable device that provides DBS and records activity from the surface of the brain. Similar to a cardiac pacemaker, this adaptive device can autoadjust its level of stimulation based on a physiologic signal—in this case, brain activity related to dyskinesia. A high dyskinesia signal indicated greater likelihood of unwanted side effects and caused the device to reduce the stimulation level. A low signal indicated a higher chance of symptoms returning and triggered an increase in stimulation.

The device was tested in two patients inside and outside of the laboratory. Neither patient reported discomfort, adverse events, or worsening symptoms. In addition, the battery used as much as 45% less energy than traditional DBS, which is an important advantage, since battery replacement requires surgery.

“Our study showed that totally implanted, adaptive DBS is feasible and can be used at home in patients,” said lead author Nicole C. Swann, PhD, Assistant Professor of Human Physiology at the University of Oregon in Eugene. “Adaptive stimulation represents one of the first major advances in DBS technology since this technique was first introduced for the treatment of Parkinson’s disease 25 years ago.”

Contact Sports May Impair Memory Temporarily

Sports-related head injuries may prevent the generation of new neurons in a brain region important for memory, said investigators.

Concussion can lead to cognitive impairments, and recent evidence indicates that subconcussive hits can cause damage. The hippocampus is particularly vulnerable. One way to test the effects of head impacts on the hippocampus is a memory assessment called the mnemonic similarity test (MST), which evaluates a person’s ability to distinguish between images that are novel, previously presented, or similar to images previously presented. Accumulating evidence suggests that MST scores are related to the hippocampus’s ability to generate new neurons.

To investigate changes in memory following sports-related head injuries, researchers assessed different types of athletes in two studies. In the first study, they compared athletes with concussion, uninjured athletes who played the same sport, same-sport athletes with musculoskeletal injuries, and healthy controls. Compared with the other three groups, concussed athletes performed worse on the MST when tested two to four weeks after their injury. The scores did not remain low, however. By the time the athletes were cleared to play, their scores had improved to normal levels.

In the second study, rugby players were given the MST before the season started, halfway through the season, and one month after their last game. Scores dropped midseason, compared with preseason scores, but recovered by the postseason assessment.

“Using a cognitive test believed to be sensitive to hippocampal neurogenesis, we found that athletes with concussion show impairments that resolve following recovery,” said lead author Melissa Danielle McCradden, PhD, a postdoctoral fellow at McMaster University in Toronto. “These findings represent, to the best of our knowledge, the first reported evidence in humans suggesting a brain change that might explain the cognitive and emotional symptoms associated with mild traumatic brain injury.”

Disrupted Brain Networks May Cause Gulf War Illness

The brains of veterans with Gulf War illness (GWI) show widespread communication abnormalities in networks that support various brain functions, researchers reported. The observed patterns of impairment provide objective neurophysiologic evidence to support the self-reported symptoms of veterans with GWI.

As many as 250,000 veterans who served in Iraq, Kuwait, and Saudi Arabia during the 1991 Gulf War may currently experience GWI. Symptoms include difficulty remembering things, trouble finding words while speaking, motor coordination, mood swings, fatigue, and chronic pain. GWI is thought to result from exposure to a mix of chemical and biological warfare agents and hazardous chemicals.

To better understand brain changes in GWI, researchers compared the brains of 22 veterans with GWI to the brains of 30 healthy veterans of similar age. Using resting state functional MRI, researchers analyzed patterns of communication among regions of the brain known to control different functions and behavior. They identified changes in functional networks related to many commonly reported GWI symptoms. Individuals with GWI showed clear deficits in neural communication in the sectors of the brain responsible for visual processing, mood regulation, motor coordination, sensory processing, and language command, but increased communication in networks related to pain perception during rest.

“The results from this study provide strong evidence of neuropathology in GWI patients from exposures to neurotoxic agents,” said lead author Kaundinya Gopinath, PhD, Assistant Professor of Radiology and Imaging Sciences at Emory University in Atlanta. Next, “the aim is to establish brain mechanisms underlying GWI, which in turn can lead to development of treatments.”

Prolonged Sedation May Cause Brain Abnormalities in Infants

Full-term infants who undergo repeated anesthesia and prolonged sedation are at risk for changes in brain development, according to investigators.

Developmental impacts of prenatal exposure to sedatives have been studied widely, but less is known about the immediate and long-term neurologic and developmental effects of prolonged sedation when administered to critically ill infants after birth. Prolonged administration of opioids and benzodiazepines, which commonly are used for infants undergoing surgery, is associated with a high incidence of drug tolerance and dependence. Although negative long-term outcomes have been associated with such drug exposures in infants, these studies could not exclude other possible causes, such as prematurity or heart problems.

To study neurologic effects of prolonged sedation, researchers conducted MRI scans on full-term infants who underwent life-saving surgery that required prolonged exposure to morphine and midazolam before one year of age. Brain imaging showed several brain MRI anomalies that were not present in healthy infants, including abnormalities in gray and white matter structures and the ventricles. The number of brain MRI abnormalities significantly correlated with the average daily dose of these sedative drugs. The higher the daily dose, the more MRI irregularities were seen. The patients also had more brain fluid and a smaller total brain volume, compared with healthy infants. This pattern has been associated with long-term neurodevelopmental outcomes such as autism spectrum disorder. Taken together, these preliminary findings indicate a potential negative impact of prolonged sedation on brain growth during the first year of life, the researchers said.

“We were surprised to find higher incidence of brain abnormalities in full-term infants who underwent life-saving surgery that required prolonged sedation,” said senior author Dusica Bajic, MD, PhD, Principal Investigator at Boston Children’s Hospital. “The constellation of MRI irregularities suggests prolonged sedation may potentially contribute to delayed brain growth.” Future investigations will explore the neural mechanisms of the observed developmental effects and whether early sedation exposure may lead to long-term neurobehavioral impacts.

The Brain Preferentially Reactivates Negative Memories During Sleep

The brain selectively reactivates negative memories during sleep, prioritizing the retention of these emotional memories, which may be of greater future relevance than neutral memories and thus more worth remembering, according to investigators.

Over the past two decades, neuroscientists have gained increased understanding of how sleep boosts and stabilizes memories in the human brain. In the current study, researchers presented 57 healthy volunteers with a series of neutral and negative images. While staring straight ahead, the volunteers saw all of the negative images on one side of their field of vision (left) and all of the neutral images on the other side (right). Because the brain processes visual information in the opposite hemisphere from where it is viewed, this method allowed researchers to “tag” one hemisphere with negative content and the other with neutral content, thus enabling them to track localized memories. Participants were then shown the previously seen images for memory tests, with some of the images shown immediately after the learning phase and the rest shown after a period of wakefulness or sleep. During all memory tests, volunteers viewed the images directly in front of them, rather than to either side, and researchers asked participants to state whether an image had originally appeared to the left or right.

Participants who stayed awake in between memory tests forgot some of the original image locations, but forgetting was similar for neutral and negative images. Participants who slept between tests, on the other hand, had a much better rate of recall for the negative images than for the neutral ones. EEG recordings made during the learning phase show that the brain has encoded the distinct types of memories in its two hemispheres, with the negative images strongly encoded in the hemisphere opposite to the side of presentation. Researchers are now analyzing data that they hypothesize will show that the waking EEG pattern corresponding to emotional memories is the same pattern that is reactivated most strongly during sleep.

“This [finding] would provide a long sought-after brain-based explanation of how sleep selectively stabilizes emotional memories,” said lead author Roy Cox, PhD, research fellow in psychiatry at Beth Israel Deaconess Medical Center in Boston. “Our research substantially advances the notion that sleep plays a fundamental and complex role in the offline reorganization of waking experiences.”

Transcranial Magnetic Stimulation Improves Memory in Older Adults

A painless and noninvasive brain stimulation technique may help improve some types of memory in older adults, investigators reported.

One possible explanation for age-related memory loss is degradation of the neural connections between the hippocampus and the cortex. Weakening of these connections may lead to difficulties in creating new memories of specific events and the locations of objects. Scientists hypothesized that strengthening the connections between the hippocampus and cortex through repetitive transcranial magnetic stimulation (TMS) may help the storage of new memories. TMS delivers painless magnetic pulses to a particular region of the brain, changing the activity of the neurons within the targeted area.

To determine whether TMS could improve memory, 15 healthy adults over the age of 64 received TMS to a part of the cortex that communicates with the hippocampus. Treatment lasted for five days. During a separate week, each participant received five days of sham treatment, in which the setup was the same, but the stimulation was too low to influence the neural connections. Before and after each five-day session, participants were asked to remember pictures of everyday objects and pictures of outdoor scenes associated with each one. The adults’ ability to recall the scenes associated with the objects improved after receiving TMS, but not after the sham treatment.

“Our study demonstrates that TMS could potentially be used as a way to improve memory for older adults experiencing age-related memory impairments,” said John A. Walker, PhD, postdoctorate fellow at Northwestern University in Evanston, Illinois. “TMS can be used to probe the relationship between brain networks and memory experimentally, opening new doors to understanding the network basis of cognitive decline in aging.”

Heading the Ball Hurts Women More Than Men

Intentionally hitting a soccer ball with the head, or “heading,” may have more adverse brain consequences for women than men, said researchers.

Heading does not typically result in a concussion, yet growing evidence links the move to CNS damage. Previous studies using diffusion tensor imaging (DTI) have revealed that heading damages the integrity of the axons. Women appear to be more vulnerable than men to problems associated with heading, as they report more symptoms that last longer, but the reason for these gender differences remains unknown.

To assess possible gender differences in the effects of heading, researchers used DTI to examine 49 male and 49 female amateur soccer players who were matched on age and frequency of heading. Higher levels of heading were associated with decreased axonal integrity in three brain regions for men and eight brain regions for women. In seven of the areas identified in women, the association between axonal integrity and heading was significantly stronger than it was in men.

“Given similar amounts of exposure to heading, women show a greater volume of abnormality that is significantly different from what is seen in men,” said lead author Todd G. Rubin, MD, a doctoral student at Albert Einstein College of Medicine in Bronx, New York. “Identifying and understanding the basis for differences in susceptibility to injury represent key steps in determining better treatments and guidelines for safer play.”

DBS Can Individualize Treatment for Parkinson’s Disease

A new approach to deep brain stimulation (DBS) adjusts itself to deliver the appropriate amount of stimulation in patients with Parkinson’s disease, according to new research. The approach could improve symptom management and reduce side effects.

DBS has been a valuable treatment for Parkinson’s disease by helping to quell the abnormal movements that are characteristic of the disease. Traditional DBS delivers a constant level of stimulation and cannot adapt if a patient’s symptoms vary over the course of a day. As a result, a patient may sometimes receive too little stimulation, which fails to control symptoms, or too much, which causes side effects such as dyskinesia.

To match stimulation to variations in patient symptoms throughout the day, researchers and engineers developed a novel implantable device that provides DBS and records activity from the surface of the brain. Similar to a cardiac pacemaker, this adaptive device can autoadjust its level of stimulation based on a physiologic signal—in this case, brain activity related to dyskinesia. A high dyskinesia signal indicated greater likelihood of unwanted side effects and caused the device to reduce the stimulation level. A low signal indicated a higher chance of symptoms returning and triggered an increase in stimulation.

The device was tested in two patients inside and outside of the laboratory. Neither patient reported discomfort, adverse events, or worsening symptoms. In addition, the battery used as much as 45% less energy than traditional DBS, which is an important advantage, since battery replacement requires surgery.

“Our study showed that totally implanted, adaptive DBS is feasible and can be used at home in patients,” said lead author Nicole C. Swann, PhD, Assistant Professor of Human Physiology at the University of Oregon in Eugene. “Adaptive stimulation represents one of the first major advances in DBS technology since this technique was first introduced for the treatment of Parkinson’s disease 25 years ago.”

Contact Sports May Impair Memory Temporarily

Sports-related head injuries may prevent the generation of new neurons in a brain region important for memory, said investigators.

Concussion can lead to cognitive impairments, and recent evidence indicates that subconcussive hits can cause damage. The hippocampus is particularly vulnerable. One way to test the effects of head impacts on the hippocampus is a memory assessment called the mnemonic similarity test (MST), which evaluates a person’s ability to distinguish between images that are novel, previously presented, or similar to images previously presented. Accumulating evidence suggests that MST scores are related to the hippocampus’s ability to generate new neurons.

To investigate changes in memory following sports-related head injuries, researchers assessed different types of athletes in two studies. In the first study, they compared athletes with concussion, uninjured athletes who played the same sport, same-sport athletes with musculoskeletal injuries, and healthy controls. Compared with the other three groups, concussed athletes performed worse on the MST when tested two to four weeks after their injury. The scores did not remain low, however. By the time the athletes were cleared to play, their scores had improved to normal levels.

In the second study, rugby players were given the MST before the season started, halfway through the season, and one month after their last game. Scores dropped midseason, compared with preseason scores, but recovered by the postseason assessment.

“Using a cognitive test believed to be sensitive to hippocampal neurogenesis, we found that athletes with concussion show impairments that resolve following recovery,” said lead author Melissa Danielle McCradden, PhD, a postdoctoral fellow at McMaster University in Toronto. “These findings represent, to the best of our knowledge, the first reported evidence in humans suggesting a brain change that might explain the cognitive and emotional symptoms associated with mild traumatic brain injury.”

Disrupted Brain Networks May Cause Gulf War Illness

The brains of veterans with Gulf War illness (GWI) show widespread communication abnormalities in networks that support various brain functions, researchers reported. The observed patterns of impairment provide objective neurophysiologic evidence to support the self-reported symptoms of veterans with GWI.

As many as 250,000 veterans who served in Iraq, Kuwait, and Saudi Arabia during the 1991 Gulf War may currently experience GWI. Symptoms include difficulty remembering things, trouble finding words while speaking, motor coordination, mood swings, fatigue, and chronic pain. GWI is thought to result from exposure to a mix of chemical and biological warfare agents and hazardous chemicals.

To better understand brain changes in GWI, researchers compared the brains of 22 veterans with GWI to the brains of 30 healthy veterans of similar age. Using resting state functional MRI, researchers analyzed patterns of communication among regions of the brain known to control different functions and behavior. They identified changes in functional networks related to many commonly reported GWI symptoms. Individuals with GWI showed clear deficits in neural communication in the sectors of the brain responsible for visual processing, mood regulation, motor coordination, sensory processing, and language command, but increased communication in networks related to pain perception during rest.

“The results from this study provide strong evidence of neuropathology in GWI patients from exposures to neurotoxic agents,” said lead author Kaundinya Gopinath, PhD, Assistant Professor of Radiology and Imaging Sciences at Emory University in Atlanta. Next, “the aim is to establish brain mechanisms underlying GWI, which in turn can lead to development of treatments.”

Prolonged Sedation May Cause Brain Abnormalities in Infants

Full-term infants who undergo repeated anesthesia and prolonged sedation are at risk for changes in brain development, according to investigators.

Developmental impacts of prenatal exposure to sedatives have been studied widely, but less is known about the immediate and long-term neurologic and developmental effects of prolonged sedation when administered to critically ill infants after birth. Prolonged administration of opioids and benzodiazepines, which commonly are used for infants undergoing surgery, is associated with a high incidence of drug tolerance and dependence. Although negative long-term outcomes have been associated with such drug exposures in infants, these studies could not exclude other possible causes, such as prematurity or heart problems.

To study neurologic effects of prolonged sedation, researchers conducted MRI scans on full-term infants who underwent life-saving surgery that required prolonged exposure to morphine and midazolam before one year of age. Brain imaging showed several brain MRI anomalies that were not present in healthy infants, including abnormalities in gray and white matter structures and the ventricles. The number of brain MRI abnormalities significantly correlated with the average daily dose of these sedative drugs. The higher the daily dose, the more MRI irregularities were seen. The patients also had more brain fluid and a smaller total brain volume, compared with healthy infants. This pattern has been associated with long-term neurodevelopmental outcomes such as autism spectrum disorder. Taken together, these preliminary findings indicate a potential negative impact of prolonged sedation on brain growth during the first year of life, the researchers said.

“We were surprised to find higher incidence of brain abnormalities in full-term infants who underwent life-saving surgery that required prolonged sedation,” said senior author Dusica Bajic, MD, PhD, Principal Investigator at Boston Children’s Hospital. “The constellation of MRI irregularities suggests prolonged sedation may potentially contribute to delayed brain growth.” Future investigations will explore the neural mechanisms of the observed developmental effects and whether early sedation exposure may lead to long-term neurobehavioral impacts.

The Brain Preferentially Reactivates Negative Memories During Sleep

The brain selectively reactivates negative memories during sleep, prioritizing the retention of these emotional memories, which may be of greater future relevance than neutral memories and thus more worth remembering, according to investigators.

Over the past two decades, neuroscientists have gained increased understanding of how sleep boosts and stabilizes memories in the human brain. In the current study, researchers presented 57 healthy volunteers with a series of neutral and negative images. While staring straight ahead, the volunteers saw all of the negative images on one side of their field of vision (left) and all of the neutral images on the other side (right). Because the brain processes visual information in the opposite hemisphere from where it is viewed, this method allowed researchers to “tag” one hemisphere with negative content and the other with neutral content, thus enabling them to track localized memories. Participants were then shown the previously seen images for memory tests, with some of the images shown immediately after the learning phase and the rest shown after a period of wakefulness or sleep. During all memory tests, volunteers viewed the images directly in front of them, rather than to either side, and researchers asked participants to state whether an image had originally appeared to the left or right.

Participants who stayed awake in between memory tests forgot some of the original image locations, but forgetting was similar for neutral and negative images. Participants who slept between tests, on the other hand, had a much better rate of recall for the negative images than for the neutral ones. EEG recordings made during the learning phase show that the brain has encoded the distinct types of memories in its two hemispheres, with the negative images strongly encoded in the hemisphere opposite to the side of presentation. Researchers are now analyzing data that they hypothesize will show that the waking EEG pattern corresponding to emotional memories is the same pattern that is reactivated most strongly during sleep.

“This [finding] would provide a long sought-after brain-based explanation of how sleep selectively stabilizes emotional memories,” said lead author Roy Cox, PhD, research fellow in psychiatry at Beth Israel Deaconess Medical Center in Boston. “Our research substantially advances the notion that sleep plays a fundamental and complex role in the offline reorganization of waking experiences.”

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

[email protected]

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

[email protected]

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

[email protected]