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Inpatient dermatologist offers three rules to diagnose by
SAN FRANCISCO – Three rules can guide inpatient dermatology for the most effective practice, according to Dr. Lindy P. Fox, director of the dermatology consultation service at the University of California, San Francisco.
First, more than one infection or etiology may account for the clinical picture, especially in immunocompromised patients. If there’s more than one morphology present, work up each one separately, she said.
Second, most cases require some degree of clinicopathologic correlation.
Third, for inpatient dermatology it helps to think of "zebras," because that’s how you’ll make the rare diagnosis, she said at the annual meeting of the Pacific Dermatologic Association.
She provided tips on some of the more common morphologies encountered in hospital dermatology:
• Morbilliform. Most commonly, morbilliform brings to mind a drug eruption, viral exanthema, graft vs. host disease (GVHD), and other entities that can present in this pattern. Rarely in immunocompromised patients, disseminated histoplasmosis, cryptococcosis, or coccidiomycosis can mimic a drug eruption, so it’s important in those situations to biopsy what you think might be a drug eruption.
Acute graft vs. host disease on average occurs 25 days after a transplant, but hyperacute GVHD occurs 14 days post transplant, so think of this before your oncologist tells you the patient’s graft hasn’t taken, she said. Two features of GVHD morbilliform eruption distinguish it from other differential diagnoses: a perifollicular accentuation, and an acral distribution around the ears, hand, and periungual areas. A patient’s nausea, vomiting, diarrhea, and hyperbilirubinemia support the diagnosis.
• Papules/papulonodules. The differential diagnosis is long – fungal diseases, septic emboli, Sweet’s syndrome, leukemia or lymphoma cutis, Kaposi sarcoma, cutaneous metastasis, and sarcoidosis, among others. But if you see purple plumb-colored papules, the list shrinks to lymphoma, Kaposi sarcoma, bacillary angiomatosis, melanoma, or cutaneous metastasis.
• Cellulitic plaques. These bring to mind cellulitis or its mimic, stasis dermatitis, as well as some deep fungal infections, carcinoma erysipeloides, neutrophilic diseases, and acute inflammatory edema of the ICU. Keep in mind that cryptococcal cellulitis is the most common presentation of Cryptococcus in an organ transplant recipient. Unlike bacterial cellulitis, it tends to be bilateral. It is almost never purely a cutaneous disease. "If you ever see Cryptococcus on the skin, you are obligated to look for the systemic source of infection," she said.
• Palpable purpura. This typically points to small or mixed-vessel vasculitis. But you can also have secondary hemorrhage into a papular process; it can be due to leukemia, lymphoma cutis, or Sweet’s syndrome; or it can be a cutaneous reaction to cytarabine. What Dr. Fox said she commonly sees are purpuric papules on the lower extremities. If looked at closely, there’s a morbilliform eruption that can spread to the trunk in a few days. Biopsy typically demonstrates spongiosis, which is a "very reassuring" sign that this is a benign and self-limiting reaction to cytarabine. The reaction may or may not recur if the patient takes the drug again. "Steroids do help, and patients do very well," she said.
• Retiform purpura. Another very long differential diagnosis can be organized by thinking about potential causes as vascular (in the vessel wall) or intravascular (in the lumen of the wall). Lumen involvement is a sign of embolization or thrombosis. "If you see concomitant thrombosis and vasculitis truly on the same day early on in lesion development, that differential diagnosis shrinks considerably. There are very few things that can do that: cryoglobulinemia, septic vasculitis, and exposure to levamisole," Dr. Fox said.
• Sclerodermoid. The long differential diagnosis includes carcinoma en cuirasse, radiation dermatitis, GVHD, scleroderma, paraffinoma, lipodermatosclerosis, scleredema, and scleromyxedema, among others. Dr. Fox said she saw an unusual presentation in a woman with "antibiotic refractory cellulitis" who had developed a migrating paraffinoma after mineral oil injections to her calves for cosmetic purposes.
• Necrotic papules/plaques. One of the many potential causes – calciphylaxis – can be thought of as analogous to a myocardial infarction that occurs in the skin, she said. Patients more often than not have a long history of vascular stenosis and medial arterial calcification. An acute thrombotic event occurs, and the patient presents with calciphylaxis with tissue ischemia, pain, and stellate purpuric plaques. "This implies that we need to think about our therapeutics differently," she said. Address the calcium, phosphorous, and parathyroid hormone, as usual, but also consider treating the thrombus with tissue plasminogen activator. Don’t use warfarin; many cases of calciphylaxis are triggered by warfarin, and the drug promotes calcification, Dr. Fox said at the annual meeting of the Pacific Dermatologic Association.
• Ulcers. The most common causes in the hospital are venous insufficiency, pyoderma gangrenosum, deep fungal infection, and chronic viral infections. Chronic herpes simplex virus frequently is the culprit in bedridden, immunosuppressed patients. "Any buttock ulcer or any decubitis ulcer that I see gets ruled out for concomitant herpes simplex virus because I find it probably more than 50% of the time," she said.
• Pustules. One cause – disseminated candidiasis – can mimic acne in the immunosuppressed patient. The lesions tend to have a pale center that sometimes is pustular. "You can KOH that center to prove that you’ve got candidiasis," she said. If there’s no pustule, diagnosing disseminated candidiasis can be difficult because the collection of organisms is so small that it’s easily missed on serial sectioning by dermatopathology. Ask for serial sectioning and staining to identify the organism.
• Erythema. Dr. Fox said she divides erythemas into macular, subacute, and erosive. Macular erythema can be a toxin-mediated erythema or due to drug eruption, GVHD, viral exanthema, or Kawasaki disease. Eosinophilia is a common finding in toxin-mediated erythema. "I use it to help rule [erythema] in, rather than to help rule it out," she said.
When a subacute or chronic erythroderma is due to drug hypersensitivity reaction, be aware of two long-term sequellae: thyroid disruption and late-onset cardiac involvement presenting as life-threatening heart failure in people you wouldn’t expect to have heart problems. Dr. Fox said she checks thyroid-stimulating hormone levels monthly for 6 months and warns patients to go to the emergency department if they develop heart symptoms and tell the staff there to call the dermatologist.
One of the lesser-known causes of erosive erythroderma is toxic erythema of chemotherapy. It can take a lot of charts and talking with the primary medical team to make sure this is not toxic erythema necrolysislike GVHD, she said.
Dr. Fox reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Three rules can guide inpatient dermatology for the most effective practice, according to Dr. Lindy P. Fox, director of the dermatology consultation service at the University of California, San Francisco.
First, more than one infection or etiology may account for the clinical picture, especially in immunocompromised patients. If there’s more than one morphology present, work up each one separately, she said.
Second, most cases require some degree of clinicopathologic correlation.
Third, for inpatient dermatology it helps to think of "zebras," because that’s how you’ll make the rare diagnosis, she said at the annual meeting of the Pacific Dermatologic Association.
She provided tips on some of the more common morphologies encountered in hospital dermatology:
• Morbilliform. Most commonly, morbilliform brings to mind a drug eruption, viral exanthema, graft vs. host disease (GVHD), and other entities that can present in this pattern. Rarely in immunocompromised patients, disseminated histoplasmosis, cryptococcosis, or coccidiomycosis can mimic a drug eruption, so it’s important in those situations to biopsy what you think might be a drug eruption.
Acute graft vs. host disease on average occurs 25 days after a transplant, but hyperacute GVHD occurs 14 days post transplant, so think of this before your oncologist tells you the patient’s graft hasn’t taken, she said. Two features of GVHD morbilliform eruption distinguish it from other differential diagnoses: a perifollicular accentuation, and an acral distribution around the ears, hand, and periungual areas. A patient’s nausea, vomiting, diarrhea, and hyperbilirubinemia support the diagnosis.
• Papules/papulonodules. The differential diagnosis is long – fungal diseases, septic emboli, Sweet’s syndrome, leukemia or lymphoma cutis, Kaposi sarcoma, cutaneous metastasis, and sarcoidosis, among others. But if you see purple plumb-colored papules, the list shrinks to lymphoma, Kaposi sarcoma, bacillary angiomatosis, melanoma, or cutaneous metastasis.
• Cellulitic plaques. These bring to mind cellulitis or its mimic, stasis dermatitis, as well as some deep fungal infections, carcinoma erysipeloides, neutrophilic diseases, and acute inflammatory edema of the ICU. Keep in mind that cryptococcal cellulitis is the most common presentation of Cryptococcus in an organ transplant recipient. Unlike bacterial cellulitis, it tends to be bilateral. It is almost never purely a cutaneous disease. "If you ever see Cryptococcus on the skin, you are obligated to look for the systemic source of infection," she said.
• Palpable purpura. This typically points to small or mixed-vessel vasculitis. But you can also have secondary hemorrhage into a papular process; it can be due to leukemia, lymphoma cutis, or Sweet’s syndrome; or it can be a cutaneous reaction to cytarabine. What Dr. Fox said she commonly sees are purpuric papules on the lower extremities. If looked at closely, there’s a morbilliform eruption that can spread to the trunk in a few days. Biopsy typically demonstrates spongiosis, which is a "very reassuring" sign that this is a benign and self-limiting reaction to cytarabine. The reaction may or may not recur if the patient takes the drug again. "Steroids do help, and patients do very well," she said.
• Retiform purpura. Another very long differential diagnosis can be organized by thinking about potential causes as vascular (in the vessel wall) or intravascular (in the lumen of the wall). Lumen involvement is a sign of embolization or thrombosis. "If you see concomitant thrombosis and vasculitis truly on the same day early on in lesion development, that differential diagnosis shrinks considerably. There are very few things that can do that: cryoglobulinemia, septic vasculitis, and exposure to levamisole," Dr. Fox said.
• Sclerodermoid. The long differential diagnosis includes carcinoma en cuirasse, radiation dermatitis, GVHD, scleroderma, paraffinoma, lipodermatosclerosis, scleredema, and scleromyxedema, among others. Dr. Fox said she saw an unusual presentation in a woman with "antibiotic refractory cellulitis" who had developed a migrating paraffinoma after mineral oil injections to her calves for cosmetic purposes.
• Necrotic papules/plaques. One of the many potential causes – calciphylaxis – can be thought of as analogous to a myocardial infarction that occurs in the skin, she said. Patients more often than not have a long history of vascular stenosis and medial arterial calcification. An acute thrombotic event occurs, and the patient presents with calciphylaxis with tissue ischemia, pain, and stellate purpuric plaques. "This implies that we need to think about our therapeutics differently," she said. Address the calcium, phosphorous, and parathyroid hormone, as usual, but also consider treating the thrombus with tissue plasminogen activator. Don’t use warfarin; many cases of calciphylaxis are triggered by warfarin, and the drug promotes calcification, Dr. Fox said at the annual meeting of the Pacific Dermatologic Association.
• Ulcers. The most common causes in the hospital are venous insufficiency, pyoderma gangrenosum, deep fungal infection, and chronic viral infections. Chronic herpes simplex virus frequently is the culprit in bedridden, immunosuppressed patients. "Any buttock ulcer or any decubitis ulcer that I see gets ruled out for concomitant herpes simplex virus because I find it probably more than 50% of the time," she said.
• Pustules. One cause – disseminated candidiasis – can mimic acne in the immunosuppressed patient. The lesions tend to have a pale center that sometimes is pustular. "You can KOH that center to prove that you’ve got candidiasis," she said. If there’s no pustule, diagnosing disseminated candidiasis can be difficult because the collection of organisms is so small that it’s easily missed on serial sectioning by dermatopathology. Ask for serial sectioning and staining to identify the organism.
• Erythema. Dr. Fox said she divides erythemas into macular, subacute, and erosive. Macular erythema can be a toxin-mediated erythema or due to drug eruption, GVHD, viral exanthema, or Kawasaki disease. Eosinophilia is a common finding in toxin-mediated erythema. "I use it to help rule [erythema] in, rather than to help rule it out," she said.
When a subacute or chronic erythroderma is due to drug hypersensitivity reaction, be aware of two long-term sequellae: thyroid disruption and late-onset cardiac involvement presenting as life-threatening heart failure in people you wouldn’t expect to have heart problems. Dr. Fox said she checks thyroid-stimulating hormone levels monthly for 6 months and warns patients to go to the emergency department if they develop heart symptoms and tell the staff there to call the dermatologist.
One of the lesser-known causes of erosive erythroderma is toxic erythema of chemotherapy. It can take a lot of charts and talking with the primary medical team to make sure this is not toxic erythema necrolysislike GVHD, she said.
Dr. Fox reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Three rules can guide inpatient dermatology for the most effective practice, according to Dr. Lindy P. Fox, director of the dermatology consultation service at the University of California, San Francisco.
First, more than one infection or etiology may account for the clinical picture, especially in immunocompromised patients. If there’s more than one morphology present, work up each one separately, she said.
Second, most cases require some degree of clinicopathologic correlation.
Third, for inpatient dermatology it helps to think of "zebras," because that’s how you’ll make the rare diagnosis, she said at the annual meeting of the Pacific Dermatologic Association.
She provided tips on some of the more common morphologies encountered in hospital dermatology:
• Morbilliform. Most commonly, morbilliform brings to mind a drug eruption, viral exanthema, graft vs. host disease (GVHD), and other entities that can present in this pattern. Rarely in immunocompromised patients, disseminated histoplasmosis, cryptococcosis, or coccidiomycosis can mimic a drug eruption, so it’s important in those situations to biopsy what you think might be a drug eruption.
Acute graft vs. host disease on average occurs 25 days after a transplant, but hyperacute GVHD occurs 14 days post transplant, so think of this before your oncologist tells you the patient’s graft hasn’t taken, she said. Two features of GVHD morbilliform eruption distinguish it from other differential diagnoses: a perifollicular accentuation, and an acral distribution around the ears, hand, and periungual areas. A patient’s nausea, vomiting, diarrhea, and hyperbilirubinemia support the diagnosis.
• Papules/papulonodules. The differential diagnosis is long – fungal diseases, septic emboli, Sweet’s syndrome, leukemia or lymphoma cutis, Kaposi sarcoma, cutaneous metastasis, and sarcoidosis, among others. But if you see purple plumb-colored papules, the list shrinks to lymphoma, Kaposi sarcoma, bacillary angiomatosis, melanoma, or cutaneous metastasis.
• Cellulitic plaques. These bring to mind cellulitis or its mimic, stasis dermatitis, as well as some deep fungal infections, carcinoma erysipeloides, neutrophilic diseases, and acute inflammatory edema of the ICU. Keep in mind that cryptococcal cellulitis is the most common presentation of Cryptococcus in an organ transplant recipient. Unlike bacterial cellulitis, it tends to be bilateral. It is almost never purely a cutaneous disease. "If you ever see Cryptococcus on the skin, you are obligated to look for the systemic source of infection," she said.
• Palpable purpura. This typically points to small or mixed-vessel vasculitis. But you can also have secondary hemorrhage into a papular process; it can be due to leukemia, lymphoma cutis, or Sweet’s syndrome; or it can be a cutaneous reaction to cytarabine. What Dr. Fox said she commonly sees are purpuric papules on the lower extremities. If looked at closely, there’s a morbilliform eruption that can spread to the trunk in a few days. Biopsy typically demonstrates spongiosis, which is a "very reassuring" sign that this is a benign and self-limiting reaction to cytarabine. The reaction may or may not recur if the patient takes the drug again. "Steroids do help, and patients do very well," she said.
• Retiform purpura. Another very long differential diagnosis can be organized by thinking about potential causes as vascular (in the vessel wall) or intravascular (in the lumen of the wall). Lumen involvement is a sign of embolization or thrombosis. "If you see concomitant thrombosis and vasculitis truly on the same day early on in lesion development, that differential diagnosis shrinks considerably. There are very few things that can do that: cryoglobulinemia, septic vasculitis, and exposure to levamisole," Dr. Fox said.
• Sclerodermoid. The long differential diagnosis includes carcinoma en cuirasse, radiation dermatitis, GVHD, scleroderma, paraffinoma, lipodermatosclerosis, scleredema, and scleromyxedema, among others. Dr. Fox said she saw an unusual presentation in a woman with "antibiotic refractory cellulitis" who had developed a migrating paraffinoma after mineral oil injections to her calves for cosmetic purposes.
• Necrotic papules/plaques. One of the many potential causes – calciphylaxis – can be thought of as analogous to a myocardial infarction that occurs in the skin, she said. Patients more often than not have a long history of vascular stenosis and medial arterial calcification. An acute thrombotic event occurs, and the patient presents with calciphylaxis with tissue ischemia, pain, and stellate purpuric plaques. "This implies that we need to think about our therapeutics differently," she said. Address the calcium, phosphorous, and parathyroid hormone, as usual, but also consider treating the thrombus with tissue plasminogen activator. Don’t use warfarin; many cases of calciphylaxis are triggered by warfarin, and the drug promotes calcification, Dr. Fox said at the annual meeting of the Pacific Dermatologic Association.
• Ulcers. The most common causes in the hospital are venous insufficiency, pyoderma gangrenosum, deep fungal infection, and chronic viral infections. Chronic herpes simplex virus frequently is the culprit in bedridden, immunosuppressed patients. "Any buttock ulcer or any decubitis ulcer that I see gets ruled out for concomitant herpes simplex virus because I find it probably more than 50% of the time," she said.
• Pustules. One cause – disseminated candidiasis – can mimic acne in the immunosuppressed patient. The lesions tend to have a pale center that sometimes is pustular. "You can KOH that center to prove that you’ve got candidiasis," she said. If there’s no pustule, diagnosing disseminated candidiasis can be difficult because the collection of organisms is so small that it’s easily missed on serial sectioning by dermatopathology. Ask for serial sectioning and staining to identify the organism.
• Erythema. Dr. Fox said she divides erythemas into macular, subacute, and erosive. Macular erythema can be a toxin-mediated erythema or due to drug eruption, GVHD, viral exanthema, or Kawasaki disease. Eosinophilia is a common finding in toxin-mediated erythema. "I use it to help rule [erythema] in, rather than to help rule it out," she said.
When a subacute or chronic erythroderma is due to drug hypersensitivity reaction, be aware of two long-term sequellae: thyroid disruption and late-onset cardiac involvement presenting as life-threatening heart failure in people you wouldn’t expect to have heart problems. Dr. Fox said she checks thyroid-stimulating hormone levels monthly for 6 months and warns patients to go to the emergency department if they develop heart symptoms and tell the staff there to call the dermatologist.
One of the lesser-known causes of erosive erythroderma is toxic erythema of chemotherapy. It can take a lot of charts and talking with the primary medical team to make sure this is not toxic erythema necrolysislike GVHD, she said.
Dr. Fox reported having no relevant financial disclosures.
On Twitter @sherryboschert
EXPERT ANALYSIS FROM THE PDA ANNUAL MEETING
FDA recommends schedule II for hydrocodone combinations
The Food and Drug Administration will recommend that products containing the narcotic hydrocodone be reclassified from Schedule III drugs to the more restrictive Schedule II, the agency announced.
This major policy shift would affect access to widely used drugs that combine hydrocodone with other medications such as acetaminophen in brand names like Vicodin, Norco, or Lortab.
The FDA’s decision comes out of years of controversy over epidemic-scale abuse and misuse of opioid products in some parts of the country and the need to balance safety with continued access to the drugs for patients who rely on them for continuous pain relief, said Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research, in a statement released online.
The move also follows a 19-10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January 2013 calling for hydrocodone combination products to be reclassified as Schedule II, as well as requests from the U.S. Drug Enforcement Administration for this action.
Under the Controlled Substances Act, Schedule II drugs usually require handwritten prescriptions with no refills, among other restrictions, while Schedule III allows written or oral prescribing and five refills within 6 months.
The FDA plans to submit formal recommendations by early December to the U.S. Department of Health and Human Services to reclassify hydrocodone combination products into Schedule II, and the agency expects that the National Institute on Drug Abuse will agree with the recommendations, which will start a process leading to a final decision by the Drug Enforcement Administration.
This is an "extremely complex" issue and a "major change" that has at least the potential to benefit patients, Dr. Adrian G. Bartoli said in a phone interview.
Hydrocodone is probably twice as potent as morphine and as potent and addictive as any Schedule II drugs, said Dr. Bartoli, a pain management specialist practicing in San Francisco. Hydrocodone has remained in Schedule III largely for historical reasons, but if it was a new drug being classified today, "it would unquestionably be a Schedule II medication," he said.
Many clinicians such as internists or surgeons will prescribe hydrocodone combination products less often if it becomes a Schedule II drug because they’ll lose the convenience of oral prescribing and refills, he predicted. The change won’t affect Dr. Bartoli’s practice because "I already see patients on a regular basis and write out a prescription for them," he said. Approximately 40% of hydrocodone combination analgesics are prescribed by primary care practitioners, according to the FDA.
Some patients who lose access to hydrocodone combination products may turn to emergency departments and urgent care centers more often for help with their pain, Dr. Bartoli predicted.
On the other hand, while there is nothing really equivalent to hydrocodone in Schedule III or IV drugs, clinicians who turn away from prescribing hydrocodone combination products may fill that vacuum with medications like tramadol, which is not a scheduled substance in most states, or buprenorphine, which falls under Schedule III, he said. Right now, those medications are on the fringe of pain management. "They’re actually excellent medications, but they’re not prescribed that often," he said.*
Whether this change would be good or bad is hard to say, he added. "Generally in my experience those medications may have less addictive potential. I think that’s a good thing for patients and overall may be an improvement in the way that pain management is being delivered right now."
Hydrocodone alone already is a Schedule II drug, but there is no single-ingredient hydrocodone product available. There are 81 products that combine hydrocodone with acetaminophen or ibuprofen and 12 cough suppressants that combine hydrocodone with chlorpheniramine, homatropine, or pseudoephedrine, according to the FDA. In 2011, there were about 131 million prescriptions for combination hydrocodone analgesic products, compared with 35 million for combinations containing oxycodone (a Schedule II drug), according to national prescription data cited by the FDA.
Dr. Bartoli has been a consultant to Purdue Pharma and to Vertical Pharmaceuticals, both of which market pain management medications.**
*This paragraph contains a correction. Dr. Bartoli was speaking of tramadol rather than trazodone.
**This story was updated 10/28/13.
On Twitter @sherryboschert
The Food and Drug Administration will recommend that products containing the narcotic hydrocodone be reclassified from Schedule III drugs to the more restrictive Schedule II, the agency announced.
This major policy shift would affect access to widely used drugs that combine hydrocodone with other medications such as acetaminophen in brand names like Vicodin, Norco, or Lortab.
The FDA’s decision comes out of years of controversy over epidemic-scale abuse and misuse of opioid products in some parts of the country and the need to balance safety with continued access to the drugs for patients who rely on them for continuous pain relief, said Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research, in a statement released online.
The move also follows a 19-10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January 2013 calling for hydrocodone combination products to be reclassified as Schedule II, as well as requests from the U.S. Drug Enforcement Administration for this action.
Under the Controlled Substances Act, Schedule II drugs usually require handwritten prescriptions with no refills, among other restrictions, while Schedule III allows written or oral prescribing and five refills within 6 months.
The FDA plans to submit formal recommendations by early December to the U.S. Department of Health and Human Services to reclassify hydrocodone combination products into Schedule II, and the agency expects that the National Institute on Drug Abuse will agree with the recommendations, which will start a process leading to a final decision by the Drug Enforcement Administration.
This is an "extremely complex" issue and a "major change" that has at least the potential to benefit patients, Dr. Adrian G. Bartoli said in a phone interview.
Hydrocodone is probably twice as potent as morphine and as potent and addictive as any Schedule II drugs, said Dr. Bartoli, a pain management specialist practicing in San Francisco. Hydrocodone has remained in Schedule III largely for historical reasons, but if it was a new drug being classified today, "it would unquestionably be a Schedule II medication," he said.
Many clinicians such as internists or surgeons will prescribe hydrocodone combination products less often if it becomes a Schedule II drug because they’ll lose the convenience of oral prescribing and refills, he predicted. The change won’t affect Dr. Bartoli’s practice because "I already see patients on a regular basis and write out a prescription for them," he said. Approximately 40% of hydrocodone combination analgesics are prescribed by primary care practitioners, according to the FDA.
Some patients who lose access to hydrocodone combination products may turn to emergency departments and urgent care centers more often for help with their pain, Dr. Bartoli predicted.
On the other hand, while there is nothing really equivalent to hydrocodone in Schedule III or IV drugs, clinicians who turn away from prescribing hydrocodone combination products may fill that vacuum with medications like tramadol, which is not a scheduled substance in most states, or buprenorphine, which falls under Schedule III, he said. Right now, those medications are on the fringe of pain management. "They’re actually excellent medications, but they’re not prescribed that often," he said.*
Whether this change would be good or bad is hard to say, he added. "Generally in my experience those medications may have less addictive potential. I think that’s a good thing for patients and overall may be an improvement in the way that pain management is being delivered right now."
Hydrocodone alone already is a Schedule II drug, but there is no single-ingredient hydrocodone product available. There are 81 products that combine hydrocodone with acetaminophen or ibuprofen and 12 cough suppressants that combine hydrocodone with chlorpheniramine, homatropine, or pseudoephedrine, according to the FDA. In 2011, there were about 131 million prescriptions for combination hydrocodone analgesic products, compared with 35 million for combinations containing oxycodone (a Schedule II drug), according to national prescription data cited by the FDA.
Dr. Bartoli has been a consultant to Purdue Pharma and to Vertical Pharmaceuticals, both of which market pain management medications.**
*This paragraph contains a correction. Dr. Bartoli was speaking of tramadol rather than trazodone.
**This story was updated 10/28/13.
On Twitter @sherryboschert
The Food and Drug Administration will recommend that products containing the narcotic hydrocodone be reclassified from Schedule III drugs to the more restrictive Schedule II, the agency announced.
This major policy shift would affect access to widely used drugs that combine hydrocodone with other medications such as acetaminophen in brand names like Vicodin, Norco, or Lortab.
The FDA’s decision comes out of years of controversy over epidemic-scale abuse and misuse of opioid products in some parts of the country and the need to balance safety with continued access to the drugs for patients who rely on them for continuous pain relief, said Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research, in a statement released online.
The move also follows a 19-10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January 2013 calling for hydrocodone combination products to be reclassified as Schedule II, as well as requests from the U.S. Drug Enforcement Administration for this action.
Under the Controlled Substances Act, Schedule II drugs usually require handwritten prescriptions with no refills, among other restrictions, while Schedule III allows written or oral prescribing and five refills within 6 months.
The FDA plans to submit formal recommendations by early December to the U.S. Department of Health and Human Services to reclassify hydrocodone combination products into Schedule II, and the agency expects that the National Institute on Drug Abuse will agree with the recommendations, which will start a process leading to a final decision by the Drug Enforcement Administration.
This is an "extremely complex" issue and a "major change" that has at least the potential to benefit patients, Dr. Adrian G. Bartoli said in a phone interview.
Hydrocodone is probably twice as potent as morphine and as potent and addictive as any Schedule II drugs, said Dr. Bartoli, a pain management specialist practicing in San Francisco. Hydrocodone has remained in Schedule III largely for historical reasons, but if it was a new drug being classified today, "it would unquestionably be a Schedule II medication," he said.
Many clinicians such as internists or surgeons will prescribe hydrocodone combination products less often if it becomes a Schedule II drug because they’ll lose the convenience of oral prescribing and refills, he predicted. The change won’t affect Dr. Bartoli’s practice because "I already see patients on a regular basis and write out a prescription for them," he said. Approximately 40% of hydrocodone combination analgesics are prescribed by primary care practitioners, according to the FDA.
Some patients who lose access to hydrocodone combination products may turn to emergency departments and urgent care centers more often for help with their pain, Dr. Bartoli predicted.
On the other hand, while there is nothing really equivalent to hydrocodone in Schedule III or IV drugs, clinicians who turn away from prescribing hydrocodone combination products may fill that vacuum with medications like tramadol, which is not a scheduled substance in most states, or buprenorphine, which falls under Schedule III, he said. Right now, those medications are on the fringe of pain management. "They’re actually excellent medications, but they’re not prescribed that often," he said.*
Whether this change would be good or bad is hard to say, he added. "Generally in my experience those medications may have less addictive potential. I think that’s a good thing for patients and overall may be an improvement in the way that pain management is being delivered right now."
Hydrocodone alone already is a Schedule II drug, but there is no single-ingredient hydrocodone product available. There are 81 products that combine hydrocodone with acetaminophen or ibuprofen and 12 cough suppressants that combine hydrocodone with chlorpheniramine, homatropine, or pseudoephedrine, according to the FDA. In 2011, there were about 131 million prescriptions for combination hydrocodone analgesic products, compared with 35 million for combinations containing oxycodone (a Schedule II drug), according to national prescription data cited by the FDA.
Dr. Bartoli has been a consultant to Purdue Pharma and to Vertical Pharmaceuticals, both of which market pain management medications.**
*This paragraph contains a correction. Dr. Bartoli was speaking of tramadol rather than trazodone.
**This story was updated 10/28/13.
On Twitter @sherryboschert
Repeat CT selectively in children with traumatic brain injuries
SAN FRANCISCO – Repeat CT scans in children with mild traumatic brain injury were not justified when done routinely but may be warranted for epidural hematomas, according to a retrospective study of 120 patients.
A comparison of the 106 patients who underwent repeat CT scans and the 14 who did not found that the two groups did not differ significantly based on their Injury Severity Score (ISS), the mechanism of injury, or the type of brain injury. Neurologic symptoms did not worsen in patients who did not get a repeat CT scan, none of whom needed surgery, Dr. Jarett K. Howe and his associates reported.
Repeat CT scans showed injury progression in 7 patients (7%), including 2 with subarachnoid hemorrhage and 5 with epidural hematoma –a third of the 15 epidural hematomas in the study. Two patients with epidural hematoma required craniotomy, one of whom showed worsening of clinical symptoms. All 106 patients who had repeat CT scans were discharged without sequelae, said Dr. Howe of Cardinal Glennon Children’s Medical Center, St. Louis University.
The investigators analyzed records for 435 children admitted with traumatic brain injury (TBI) between July 2004 and July 2012 who had CT evidence of an intracranial hemorrhage and a Glasgow Coma Scale score of 14-15, 120 of whom had complete data and met no exclusion criteria.
Children who got a repeat CT scan were significantly older (8 years of age) than those who didn’t (3 years), Dr. Howe reported at the annual meeting of the American Association for the Surgery of Trauma. "This is particularly interesting since CT scan usage is often justified by the difficulty in examining a young child," he said.
The mean Injury Severity Score was similar between groups: 15 in those scanned and 13 in those not scanned.
Although the type of injury did not influence the likelihood of repeat CT, all 15 patients with epidural hematoma got a repeat CT scan (100%), he noted. Repeat CT scans also were ordered in 94% of patients with subdural hematoma, 71% with contusion, 88% with intraparenchymal hemorrhage, 77% with subarachnoid hemorrhage, and 67% with intraventricular hemorrhage.
The TBIs were caused primarily by falls or motor vehicle accidents but also by assaults, sports, or being hit by a car as a pedestrian.
Every year in the United States approximately 642,000 children are evaluated in emergency departments for TBI, 65,000 are admitted, and 7,400 die of TBI. As many as 70% of these children get imaged, with head CT, the diagnostic modality of choice, Dr. Howe said. A total of 4%-8% of children undergoing a CT will have a skull or intracranial abnormality, and less than 1% will have an injury requiring neurosurgical intervention.
Radiation from the CT scan, however, may cause a fatal cancer later on in 1 of every 1,200 children scanned, an extrapolation of historical data from Hiroshima, Japan suggests, he said.
"A majority of our children with minor physiologic insults can be managed without repeat imaging," he said. The investigators now are organizing a multi-institutional study to validate the findings.
A previous prospective study that evaluated 42,412 children with head injuries found that 90% had isolated head trauma and 97% had a Glasgow Coma Scale score of 15 upon arrival in emergency rooms. Still, 35% underwent head CT scans, which identified TBI in 5%, and 0.4% underwent surgery. No patients died (Lancet 2009;374:1160-70).
Previous studies in adults also suggest that repeat CT is not necessary for mild TBI because patients requiring intervention will show deterioration on physical exam, Dr. Howe added. Repeat CT showed injury progression in 21% of 179 adults in one study, only 7 of whom needed surgical intervention (J. Trauma 2006;60:494-9).
Dr. Howe reported having no financial disclosures.
On Twitter @sherryboschert
Intuitively, this makes sense, and it’s something we want to believe.
No patient in the selective CT group developed progression of neurologic symptoms or required delayed intervention. In contrast, 7% of children undergoing scheduled or routine CT demonstrated progression, and a majority had epidural hematoma. Two required operative intervention, both as a result of expanding epidural hematoma. From this, the authors conclude that routine or scheduled CT is not indicated in absence of progression or epidural hematoma.
As I understand it, the purpose for repeat CT is to detect progression and the need for intervention. A consistent observation in a review of the literature demonstrates a wide discrepancy in the reported rates of CT progression with or without neurologic progression. Can we safely observe all lesions other than subdural hematoma and obtain CT only if neurologic symptoms progress? If so, for how long do we observe these patients?
The study has a limited number of patients. An appropriately powered noninferiority study to show a new treatment, selective CT, is not worse than existing CT would require nearly 6,000 patients in each arm.
The study provides a description of the lesions noted on CT in the two groups by type, yet it is difficult to determine if the two groups were truly comparable, since there’s a great deal of variability between lesions. Further complicating the analysis is not only the type of lesion but the location of the lesion. Outcomes between supratentorial and posterior fossa lesions can be significantly different regardless of the volume of blood. The findings also could have been influenced by the volume of blood and the time from initial injury to evaluation and imaging.
Dr. Denis D. Bensard is chief of pediatric surgery and trauma at Denver Health Medical Center. These are excerpts of his remarks as discussant of the study at the meeting. He reported having no financial disclosures.
Intuitively, this makes sense, and it’s something we want to believe.
No patient in the selective CT group developed progression of neurologic symptoms or required delayed intervention. In contrast, 7% of children undergoing scheduled or routine CT demonstrated progression, and a majority had epidural hematoma. Two required operative intervention, both as a result of expanding epidural hematoma. From this, the authors conclude that routine or scheduled CT is not indicated in absence of progression or epidural hematoma.
As I understand it, the purpose for repeat CT is to detect progression and the need for intervention. A consistent observation in a review of the literature demonstrates a wide discrepancy in the reported rates of CT progression with or without neurologic progression. Can we safely observe all lesions other than subdural hematoma and obtain CT only if neurologic symptoms progress? If so, for how long do we observe these patients?
The study has a limited number of patients. An appropriately powered noninferiority study to show a new treatment, selective CT, is not worse than existing CT would require nearly 6,000 patients in each arm.
The study provides a description of the lesions noted on CT in the two groups by type, yet it is difficult to determine if the two groups were truly comparable, since there’s a great deal of variability between lesions. Further complicating the analysis is not only the type of lesion but the location of the lesion. Outcomes between supratentorial and posterior fossa lesions can be significantly different regardless of the volume of blood. The findings also could have been influenced by the volume of blood and the time from initial injury to evaluation and imaging.
Dr. Denis D. Bensard is chief of pediatric surgery and trauma at Denver Health Medical Center. These are excerpts of his remarks as discussant of the study at the meeting. He reported having no financial disclosures.
Intuitively, this makes sense, and it’s something we want to believe.
No patient in the selective CT group developed progression of neurologic symptoms or required delayed intervention. In contrast, 7% of children undergoing scheduled or routine CT demonstrated progression, and a majority had epidural hematoma. Two required operative intervention, both as a result of expanding epidural hematoma. From this, the authors conclude that routine or scheduled CT is not indicated in absence of progression or epidural hematoma.
As I understand it, the purpose for repeat CT is to detect progression and the need for intervention. A consistent observation in a review of the literature demonstrates a wide discrepancy in the reported rates of CT progression with or without neurologic progression. Can we safely observe all lesions other than subdural hematoma and obtain CT only if neurologic symptoms progress? If so, for how long do we observe these patients?
The study has a limited number of patients. An appropriately powered noninferiority study to show a new treatment, selective CT, is not worse than existing CT would require nearly 6,000 patients in each arm.
The study provides a description of the lesions noted on CT in the two groups by type, yet it is difficult to determine if the two groups were truly comparable, since there’s a great deal of variability between lesions. Further complicating the analysis is not only the type of lesion but the location of the lesion. Outcomes between supratentorial and posterior fossa lesions can be significantly different regardless of the volume of blood. The findings also could have been influenced by the volume of blood and the time from initial injury to evaluation and imaging.
Dr. Denis D. Bensard is chief of pediatric surgery and trauma at Denver Health Medical Center. These are excerpts of his remarks as discussant of the study at the meeting. He reported having no financial disclosures.
SAN FRANCISCO – Repeat CT scans in children with mild traumatic brain injury were not justified when done routinely but may be warranted for epidural hematomas, according to a retrospective study of 120 patients.
A comparison of the 106 patients who underwent repeat CT scans and the 14 who did not found that the two groups did not differ significantly based on their Injury Severity Score (ISS), the mechanism of injury, or the type of brain injury. Neurologic symptoms did not worsen in patients who did not get a repeat CT scan, none of whom needed surgery, Dr. Jarett K. Howe and his associates reported.
Repeat CT scans showed injury progression in 7 patients (7%), including 2 with subarachnoid hemorrhage and 5 with epidural hematoma –a third of the 15 epidural hematomas in the study. Two patients with epidural hematoma required craniotomy, one of whom showed worsening of clinical symptoms. All 106 patients who had repeat CT scans were discharged without sequelae, said Dr. Howe of Cardinal Glennon Children’s Medical Center, St. Louis University.
The investigators analyzed records for 435 children admitted with traumatic brain injury (TBI) between July 2004 and July 2012 who had CT evidence of an intracranial hemorrhage and a Glasgow Coma Scale score of 14-15, 120 of whom had complete data and met no exclusion criteria.
Children who got a repeat CT scan were significantly older (8 years of age) than those who didn’t (3 years), Dr. Howe reported at the annual meeting of the American Association for the Surgery of Trauma. "This is particularly interesting since CT scan usage is often justified by the difficulty in examining a young child," he said.
The mean Injury Severity Score was similar between groups: 15 in those scanned and 13 in those not scanned.
Although the type of injury did not influence the likelihood of repeat CT, all 15 patients with epidural hematoma got a repeat CT scan (100%), he noted. Repeat CT scans also were ordered in 94% of patients with subdural hematoma, 71% with contusion, 88% with intraparenchymal hemorrhage, 77% with subarachnoid hemorrhage, and 67% with intraventricular hemorrhage.
The TBIs were caused primarily by falls or motor vehicle accidents but also by assaults, sports, or being hit by a car as a pedestrian.
Every year in the United States approximately 642,000 children are evaluated in emergency departments for TBI, 65,000 are admitted, and 7,400 die of TBI. As many as 70% of these children get imaged, with head CT, the diagnostic modality of choice, Dr. Howe said. A total of 4%-8% of children undergoing a CT will have a skull or intracranial abnormality, and less than 1% will have an injury requiring neurosurgical intervention.
Radiation from the CT scan, however, may cause a fatal cancer later on in 1 of every 1,200 children scanned, an extrapolation of historical data from Hiroshima, Japan suggests, he said.
"A majority of our children with minor physiologic insults can be managed without repeat imaging," he said. The investigators now are organizing a multi-institutional study to validate the findings.
A previous prospective study that evaluated 42,412 children with head injuries found that 90% had isolated head trauma and 97% had a Glasgow Coma Scale score of 15 upon arrival in emergency rooms. Still, 35% underwent head CT scans, which identified TBI in 5%, and 0.4% underwent surgery. No patients died (Lancet 2009;374:1160-70).
Previous studies in adults also suggest that repeat CT is not necessary for mild TBI because patients requiring intervention will show deterioration on physical exam, Dr. Howe added. Repeat CT showed injury progression in 21% of 179 adults in one study, only 7 of whom needed surgical intervention (J. Trauma 2006;60:494-9).
Dr. Howe reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Repeat CT scans in children with mild traumatic brain injury were not justified when done routinely but may be warranted for epidural hematomas, according to a retrospective study of 120 patients.
A comparison of the 106 patients who underwent repeat CT scans and the 14 who did not found that the two groups did not differ significantly based on their Injury Severity Score (ISS), the mechanism of injury, or the type of brain injury. Neurologic symptoms did not worsen in patients who did not get a repeat CT scan, none of whom needed surgery, Dr. Jarett K. Howe and his associates reported.
Repeat CT scans showed injury progression in 7 patients (7%), including 2 with subarachnoid hemorrhage and 5 with epidural hematoma –a third of the 15 epidural hematomas in the study. Two patients with epidural hematoma required craniotomy, one of whom showed worsening of clinical symptoms. All 106 patients who had repeat CT scans were discharged without sequelae, said Dr. Howe of Cardinal Glennon Children’s Medical Center, St. Louis University.
The investigators analyzed records for 435 children admitted with traumatic brain injury (TBI) between July 2004 and July 2012 who had CT evidence of an intracranial hemorrhage and a Glasgow Coma Scale score of 14-15, 120 of whom had complete data and met no exclusion criteria.
Children who got a repeat CT scan were significantly older (8 years of age) than those who didn’t (3 years), Dr. Howe reported at the annual meeting of the American Association for the Surgery of Trauma. "This is particularly interesting since CT scan usage is often justified by the difficulty in examining a young child," he said.
The mean Injury Severity Score was similar between groups: 15 in those scanned and 13 in those not scanned.
Although the type of injury did not influence the likelihood of repeat CT, all 15 patients with epidural hematoma got a repeat CT scan (100%), he noted. Repeat CT scans also were ordered in 94% of patients with subdural hematoma, 71% with contusion, 88% with intraparenchymal hemorrhage, 77% with subarachnoid hemorrhage, and 67% with intraventricular hemorrhage.
The TBIs were caused primarily by falls or motor vehicle accidents but also by assaults, sports, or being hit by a car as a pedestrian.
Every year in the United States approximately 642,000 children are evaluated in emergency departments for TBI, 65,000 are admitted, and 7,400 die of TBI. As many as 70% of these children get imaged, with head CT, the diagnostic modality of choice, Dr. Howe said. A total of 4%-8% of children undergoing a CT will have a skull or intracranial abnormality, and less than 1% will have an injury requiring neurosurgical intervention.
Radiation from the CT scan, however, may cause a fatal cancer later on in 1 of every 1,200 children scanned, an extrapolation of historical data from Hiroshima, Japan suggests, he said.
"A majority of our children with minor physiologic insults can be managed without repeat imaging," he said. The investigators now are organizing a multi-institutional study to validate the findings.
A previous prospective study that evaluated 42,412 children with head injuries found that 90% had isolated head trauma and 97% had a Glasgow Coma Scale score of 15 upon arrival in emergency rooms. Still, 35% underwent head CT scans, which identified TBI in 5%, and 0.4% underwent surgery. No patients died (Lancet 2009;374:1160-70).
Previous studies in adults also suggest that repeat CT is not necessary for mild TBI because patients requiring intervention will show deterioration on physical exam, Dr. Howe added. Repeat CT showed injury progression in 21% of 179 adults in one study, only 7 of whom needed surgical intervention (J. Trauma 2006;60:494-9).
Dr. Howe reported having no financial disclosures.
On Twitter @sherryboschert
AT THE AAST ANNUAL MEETING
Major finding: Two of 106 children with mild TBI who had repeat CT scans underwent craniotomy (2%), 1 of whom had worsening clinical symptoms.
Data source: Retrospective review of 120 children evaluated for mild TBI at one institution.
Disclosures: Dr. Howe reported having no financial disclosures.
Mixed results with angiography for splenic injuries
SAN FRANCISCO – Trauma centers that nonselectively performed angiography on patients with high-grade blunt splenic injury did not significantly reduce the likelihood of delayed splenectomy in a retrospective analysis of data on 6,870 patients treated at 267 hospitals.
On an individual patient level, however, use of angiography was associated with a reduced risk of delayed splenectomy (more than 6 hours after admission) after researchers controlled for the influence of multiple other factors, Dr. Ben L. Zarzaur and his associates reported at the annual meeting of the American Association for the Surgery of Trauma.
These somewhat conflicting findings suggest that "nonselective protocol-driven use of angiography at the hospital in the setting of high-grade blunt splenic injury does not benefit in terms of splenic salvage. Angiography use should be tailored to the individual patient," said Dr. Zarzaur of the University of Tennessee, Memphis.
"Attention should be paid to overall injury severity and splenic injury severity" because more severe injuries were associated with delayed splenectomy in the study, he said, adding, "Particular attention should be considered for screening for splenic vascular abnormalities."
The investigators used data from the National Trauma Data Bank (NTDB) on adults treated for high-grade blunt splenic injury at Level I or II trauma centers that admitted at least 10 such patients in 2007-2010, with high-grade injury defined as Abbreviated Injury Scale grade 3 or higher. They stratified hospital angiography use as none, low (in less than 20% of patients with high-grade blunt splenic injury), or high (in 20% or more of these patients).
Approximately 30% of patients at high-angiography centers underwent urgent splenectomy, compared with 33%-36% at hospitals with no or low-angiography use, a difference that was statistically significant. While the likelihood of a delayed splenectomy was 33% higher at low-angiography hospitals and 49% higher at hospitals without angiography, compared with high-angiography hospitals, these differences were not significant, Dr. Zarzaur reported.
The investigators used the classification of hospitals – no-, low-, or high-angiography use – to represent the three schools of thought that have developed over the past few decades regarding angiography for patients with blunt splenic injury who do not undergo immediate urgent splenectomy. The minimalist school of thought recommends using observation, not angiography for blunt splenic injury. The maximalist school of thought favors protocol-driven use of angiography for patients with certain grades of spleen injury. In between, physicians who favor a selective strategy use CT or clinical criteria or both to try and identify patients at high risk for delayed splenectomy, and reserve the risks of angiography for those patients, he said.
They chose a cutoff of 20% angiography use in patients with high-grade blunt splenic injury to discriminate between low- and high-angiography use because that represented the 90th percentile for all trauma centers in the study.
Nine percent of patients were treated at hospitals that did not use angiography for blunt splenic injury, 66% at low-angiography hospitals, and 25% at high-angiography hospitals.
Patients with grade 5 blunt splenic injury were more than twice as likely to need delayed splenectomy, compared with patients with grade 3 or 4 injury. Higher overall Injury Severity Scores (10 or higher) also doubled the risk for delayed splenectomy.
Patients with grades 4 or 5 blunt splenic injury were significantly more likely to undergo angiography at high-angiography centers than at low-angiography centers. High-angiography centers were more likely than were low-angiography centers to remove spleens with grade 5 injury after angiography, though this difference did not reach statistical significance.
Continuing controversy around the use of angiography for blunt splenic injury is illustrated by a 2011 survey of members of the American Association for the Surgery of Trauma. Members favored observation, not angiography, for grades 1 and 2 spleen injuries but showed no consensus on higher-grade injuries (J. Trauma 2011;70:1026-31).
A recent study of 1,275 patients treated for blunt splenic injury at four trauma centers that showed a significantly better chance of saving the spleen at hospitals with higher use of splenic artery embolization, especially in patients with higher-grade splenic injury (J. Trauma Acute Care Surg. 2013;75:69-74).
The current study excluded patients who died on arrival at the hospital, patients who were admitted more than 24 hours after injury, and patients who underwent splenectomy within 6 hours of admission (early splenectomy).
Dr. Zarzaur reported having no financial disclosures.
On Twitter @sherryboschert
Almost 20 years after the initial description and 30 years after we began using splenic angiography in the management of blunt splenic injury, why is it that we simply can’t settle this question? When is splenic angiography and/or catheter therapy useful in high-grade injuries?
In this study, the authors have reviewed the National Trauma Data Bank (NTDB) and have demonstrated that, at hospitals that use angiography more frequently than other hospitals, the rate of delayed splenectomy in high-grade splenic injury (defined as grades 3-5) is not different. They suggest that angiography should be selective, with particular attention to screening for vascular abnormalities.
 |
|
The authors collected information on both angiography and angiography with embolization. However, in the manuscript and the talk, they only refer to high-angiography centers. This seems to me to be a fundamental problem. This is particularly true because recent data from Jacksonville suggest that embolization of truly high-grade injury such as grade 4 injuries (even in the absence of blush) improves the salvage rate of nonoperative management.
In addition, the authors selected 20% as their cutoff for high- and low-angiography centers because 20% represented the 90th percentile of centers with regard to angiography use. I think that’s French for "it made the data analyzable." However, 20% is relatively low. If the authors wish to look at nonselective angiography they should look at us. We’re maximalists. We do angiography on 100% of patients with grades 3, 4 and 5 injuries. That’s nonselective use of angiography.
The intelligent use of this technique requires interpretation of CT and then the details of the patient presentation. For instance, a grade 4 splenic injury with or without blush but no hemoperitoneum and a totally stable patient is, in my mind, amenable to catheter therapy. Another patient with a grade 4 injury and reactive extravasation outside of the spleen and a huge peritoneum is probably best served by operative exploration. Both are grade 4 injuries, but the patients are fundamentally different.
The authors’ conclusions suggest that there is a relationship between splenic vascular injury identified on CT and success or failure of nonoperative management. This is clearly the authors’ prejudice, as they have published these findings a number of times. We’ve known for years, thanks to work from the authors’ institution, that expectant management of a patient with blush on CT fails 70% of the time and a significant number of the blushes are seen on day 3 but not day 1. Since the authors have absolutely no information on the presence or absence of blush in this data set, I fail to see how that can be one of their conclusions.
How, then, can we make sense of this? I believe the answer is in the manuscript’s last paragraph, which begins, "Another limitation of this study stems from the limitations of the NTDB." There’s little doubt that the NTDB can record an accurate snapshot of practice in the United States, but in my mind, it lacks the specificity to really answer the question, when is splenic angiography useful in high-grade injuries?
The authors have no information on presence of absence of blush, hemodynamic status other than at admission, blood transfusion rate, or technique of embolization, and they recognize that some of the data may not be accurate. I just don’t believe that the NTDB can actually answer this question.
In the end, rules are rarely helpful in the care of patients. Intelligent application of innovative techniques cannot solely be governed by rules. Perhaps the take-home message here is that the use of angiography and embolization to treat higher-grade splenic injuries is perhaps not something that everybody should be using. It may be that this technique is best preserved for high-volume centers with a real interest and a real expertise in this subject.
Dr. Thomas M. Scalea is a professor of surgery at the University of Maryland, Baltimore. These are excerpts of his remarks as a discussant of the study at the meeting. He reported having no financial disclosures.
Almost 20 years after the initial description and 30 years after we began using splenic angiography in the management of blunt splenic injury, why is it that we simply can’t settle this question? When is splenic angiography and/or catheter therapy useful in high-grade injuries?
In this study, the authors have reviewed the National Trauma Data Bank (NTDB) and have demonstrated that, at hospitals that use angiography more frequently than other hospitals, the rate of delayed splenectomy in high-grade splenic injury (defined as grades 3-5) is not different. They suggest that angiography should be selective, with particular attention to screening for vascular abnormalities.
|
|
The authors collected information on both angiography and angiography with embolization. However, in the manuscript and the talk, they only refer to high-angiography centers. This seems to me to be a fundamental problem. This is particularly true because recent data from Jacksonville suggest that embolization of truly high-grade injury such as grade 4 injuries (even in the absence of blush) improves the salvage rate of nonoperative management.
In addition, the authors selected 20% as their cutoff for high- and low-angiography centers because 20% represented the 90th percentile of centers with regard to angiography use. I think that’s French for "it made the data analyzable." However, 20% is relatively low. If the authors wish to look at nonselective angiography they should look at us. We’re maximalists. We do angiography on 100% of patients with grades 3, 4 and 5 injuries. That’s nonselective use of angiography.
The intelligent use of this technique requires interpretation of CT and then the details of the patient presentation. For instance, a grade 4 splenic injury with or without blush but no hemoperitoneum and a totally stable patient is, in my mind, amenable to catheter therapy. Another patient with a grade 4 injury and reactive extravasation outside of the spleen and a huge peritoneum is probably best served by operative exploration. Both are grade 4 injuries, but the patients are fundamentally different.
The authors’ conclusions suggest that there is a relationship between splenic vascular injury identified on CT and success or failure of nonoperative management. This is clearly the authors’ prejudice, as they have published these findings a number of times. We’ve known for years, thanks to work from the authors’ institution, that expectant management of a patient with blush on CT fails 70% of the time and a significant number of the blushes are seen on day 3 but not day 1. Since the authors have absolutely no information on the presence or absence of blush in this data set, I fail to see how that can be one of their conclusions.
How, then, can we make sense of this? I believe the answer is in the manuscript’s last paragraph, which begins, "Another limitation of this study stems from the limitations of the NTDB." There’s little doubt that the NTDB can record an accurate snapshot of practice in the United States, but in my mind, it lacks the specificity to really answer the question, when is splenic angiography useful in high-grade injuries?
The authors have no information on presence of absence of blush, hemodynamic status other than at admission, blood transfusion rate, or technique of embolization, and they recognize that some of the data may not be accurate. I just don’t believe that the NTDB can actually answer this question.
In the end, rules are rarely helpful in the care of patients. Intelligent application of innovative techniques cannot solely be governed by rules. Perhaps the take-home message here is that the use of angiography and embolization to treat higher-grade splenic injuries is perhaps not something that everybody should be using. It may be that this technique is best preserved for high-volume centers with a real interest and a real expertise in this subject.
Dr. Thomas M. Scalea is a professor of surgery at the University of Maryland, Baltimore. These are excerpts of his remarks as a discussant of the study at the meeting. He reported having no financial disclosures.
Almost 20 years after the initial description and 30 years after we began using splenic angiography in the management of blunt splenic injury, why is it that we simply can’t settle this question? When is splenic angiography and/or catheter therapy useful in high-grade injuries?
In this study, the authors have reviewed the National Trauma Data Bank (NTDB) and have demonstrated that, at hospitals that use angiography more frequently than other hospitals, the rate of delayed splenectomy in high-grade splenic injury (defined as grades 3-5) is not different. They suggest that angiography should be selective, with particular attention to screening for vascular abnormalities.
|
|
The authors collected information on both angiography and angiography with embolization. However, in the manuscript and the talk, they only refer to high-angiography centers. This seems to me to be a fundamental problem. This is particularly true because recent data from Jacksonville suggest that embolization of truly high-grade injury such as grade 4 injuries (even in the absence of blush) improves the salvage rate of nonoperative management.
In addition, the authors selected 20% as their cutoff for high- and low-angiography centers because 20% represented the 90th percentile of centers with regard to angiography use. I think that’s French for "it made the data analyzable." However, 20% is relatively low. If the authors wish to look at nonselective angiography they should look at us. We’re maximalists. We do angiography on 100% of patients with grades 3, 4 and 5 injuries. That’s nonselective use of angiography.
The intelligent use of this technique requires interpretation of CT and then the details of the patient presentation. For instance, a grade 4 splenic injury with or without blush but no hemoperitoneum and a totally stable patient is, in my mind, amenable to catheter therapy. Another patient with a grade 4 injury and reactive extravasation outside of the spleen and a huge peritoneum is probably best served by operative exploration. Both are grade 4 injuries, but the patients are fundamentally different.
The authors’ conclusions suggest that there is a relationship between splenic vascular injury identified on CT and success or failure of nonoperative management. This is clearly the authors’ prejudice, as they have published these findings a number of times. We’ve known for years, thanks to work from the authors’ institution, that expectant management of a patient with blush on CT fails 70% of the time and a significant number of the blushes are seen on day 3 but not day 1. Since the authors have absolutely no information on the presence or absence of blush in this data set, I fail to see how that can be one of their conclusions.
How, then, can we make sense of this? I believe the answer is in the manuscript’s last paragraph, which begins, "Another limitation of this study stems from the limitations of the NTDB." There’s little doubt that the NTDB can record an accurate snapshot of practice in the United States, but in my mind, it lacks the specificity to really answer the question, when is splenic angiography useful in high-grade injuries?
The authors have no information on presence of absence of blush, hemodynamic status other than at admission, blood transfusion rate, or technique of embolization, and they recognize that some of the data may not be accurate. I just don’t believe that the NTDB can actually answer this question.
In the end, rules are rarely helpful in the care of patients. Intelligent application of innovative techniques cannot solely be governed by rules. Perhaps the take-home message here is that the use of angiography and embolization to treat higher-grade splenic injuries is perhaps not something that everybody should be using. It may be that this technique is best preserved for high-volume centers with a real interest and a real expertise in this subject.
Dr. Thomas M. Scalea is a professor of surgery at the University of Maryland, Baltimore. These are excerpts of his remarks as a discussant of the study at the meeting. He reported having no financial disclosures.
SAN FRANCISCO – Trauma centers that nonselectively performed angiography on patients with high-grade blunt splenic injury did not significantly reduce the likelihood of delayed splenectomy in a retrospective analysis of data on 6,870 patients treated at 267 hospitals.
On an individual patient level, however, use of angiography was associated with a reduced risk of delayed splenectomy (more than 6 hours after admission) after researchers controlled for the influence of multiple other factors, Dr. Ben L. Zarzaur and his associates reported at the annual meeting of the American Association for the Surgery of Trauma.
These somewhat conflicting findings suggest that "nonselective protocol-driven use of angiography at the hospital in the setting of high-grade blunt splenic injury does not benefit in terms of splenic salvage. Angiography use should be tailored to the individual patient," said Dr. Zarzaur of the University of Tennessee, Memphis.
"Attention should be paid to overall injury severity and splenic injury severity" because more severe injuries were associated with delayed splenectomy in the study, he said, adding, "Particular attention should be considered for screening for splenic vascular abnormalities."
The investigators used data from the National Trauma Data Bank (NTDB) on adults treated for high-grade blunt splenic injury at Level I or II trauma centers that admitted at least 10 such patients in 2007-2010, with high-grade injury defined as Abbreviated Injury Scale grade 3 or higher. They stratified hospital angiography use as none, low (in less than 20% of patients with high-grade blunt splenic injury), or high (in 20% or more of these patients).
Approximately 30% of patients at high-angiography centers underwent urgent splenectomy, compared with 33%-36% at hospitals with no or low-angiography use, a difference that was statistically significant. While the likelihood of a delayed splenectomy was 33% higher at low-angiography hospitals and 49% higher at hospitals without angiography, compared with high-angiography hospitals, these differences were not significant, Dr. Zarzaur reported.
The investigators used the classification of hospitals – no-, low-, or high-angiography use – to represent the three schools of thought that have developed over the past few decades regarding angiography for patients with blunt splenic injury who do not undergo immediate urgent splenectomy. The minimalist school of thought recommends using observation, not angiography for blunt splenic injury. The maximalist school of thought favors protocol-driven use of angiography for patients with certain grades of spleen injury. In between, physicians who favor a selective strategy use CT or clinical criteria or both to try and identify patients at high risk for delayed splenectomy, and reserve the risks of angiography for those patients, he said.
They chose a cutoff of 20% angiography use in patients with high-grade blunt splenic injury to discriminate between low- and high-angiography use because that represented the 90th percentile for all trauma centers in the study.
Nine percent of patients were treated at hospitals that did not use angiography for blunt splenic injury, 66% at low-angiography hospitals, and 25% at high-angiography hospitals.
Patients with grade 5 blunt splenic injury were more than twice as likely to need delayed splenectomy, compared with patients with grade 3 or 4 injury. Higher overall Injury Severity Scores (10 or higher) also doubled the risk for delayed splenectomy.
Patients with grades 4 or 5 blunt splenic injury were significantly more likely to undergo angiography at high-angiography centers than at low-angiography centers. High-angiography centers were more likely than were low-angiography centers to remove spleens with grade 5 injury after angiography, though this difference did not reach statistical significance.
Continuing controversy around the use of angiography for blunt splenic injury is illustrated by a 2011 survey of members of the American Association for the Surgery of Trauma. Members favored observation, not angiography, for grades 1 and 2 spleen injuries but showed no consensus on higher-grade injuries (J. Trauma 2011;70:1026-31).
A recent study of 1,275 patients treated for blunt splenic injury at four trauma centers that showed a significantly better chance of saving the spleen at hospitals with higher use of splenic artery embolization, especially in patients with higher-grade splenic injury (J. Trauma Acute Care Surg. 2013;75:69-74).
The current study excluded patients who died on arrival at the hospital, patients who were admitted more than 24 hours after injury, and patients who underwent splenectomy within 6 hours of admission (early splenectomy).
Dr. Zarzaur reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Trauma centers that nonselectively performed angiography on patients with high-grade blunt splenic injury did not significantly reduce the likelihood of delayed splenectomy in a retrospective analysis of data on 6,870 patients treated at 267 hospitals.
On an individual patient level, however, use of angiography was associated with a reduced risk of delayed splenectomy (more than 6 hours after admission) after researchers controlled for the influence of multiple other factors, Dr. Ben L. Zarzaur and his associates reported at the annual meeting of the American Association for the Surgery of Trauma.
These somewhat conflicting findings suggest that "nonselective protocol-driven use of angiography at the hospital in the setting of high-grade blunt splenic injury does not benefit in terms of splenic salvage. Angiography use should be tailored to the individual patient," said Dr. Zarzaur of the University of Tennessee, Memphis.
"Attention should be paid to overall injury severity and splenic injury severity" because more severe injuries were associated with delayed splenectomy in the study, he said, adding, "Particular attention should be considered for screening for splenic vascular abnormalities."
The investigators used data from the National Trauma Data Bank (NTDB) on adults treated for high-grade blunt splenic injury at Level I or II trauma centers that admitted at least 10 such patients in 2007-2010, with high-grade injury defined as Abbreviated Injury Scale grade 3 or higher. They stratified hospital angiography use as none, low (in less than 20% of patients with high-grade blunt splenic injury), or high (in 20% or more of these patients).
Approximately 30% of patients at high-angiography centers underwent urgent splenectomy, compared with 33%-36% at hospitals with no or low-angiography use, a difference that was statistically significant. While the likelihood of a delayed splenectomy was 33% higher at low-angiography hospitals and 49% higher at hospitals without angiography, compared with high-angiography hospitals, these differences were not significant, Dr. Zarzaur reported.
The investigators used the classification of hospitals – no-, low-, or high-angiography use – to represent the three schools of thought that have developed over the past few decades regarding angiography for patients with blunt splenic injury who do not undergo immediate urgent splenectomy. The minimalist school of thought recommends using observation, not angiography for blunt splenic injury. The maximalist school of thought favors protocol-driven use of angiography for patients with certain grades of spleen injury. In between, physicians who favor a selective strategy use CT or clinical criteria or both to try and identify patients at high risk for delayed splenectomy, and reserve the risks of angiography for those patients, he said.
They chose a cutoff of 20% angiography use in patients with high-grade blunt splenic injury to discriminate between low- and high-angiography use because that represented the 90th percentile for all trauma centers in the study.
Nine percent of patients were treated at hospitals that did not use angiography for blunt splenic injury, 66% at low-angiography hospitals, and 25% at high-angiography hospitals.
Patients with grade 5 blunt splenic injury were more than twice as likely to need delayed splenectomy, compared with patients with grade 3 or 4 injury. Higher overall Injury Severity Scores (10 or higher) also doubled the risk for delayed splenectomy.
Patients with grades 4 or 5 blunt splenic injury were significantly more likely to undergo angiography at high-angiography centers than at low-angiography centers. High-angiography centers were more likely than were low-angiography centers to remove spleens with grade 5 injury after angiography, though this difference did not reach statistical significance.
Continuing controversy around the use of angiography for blunt splenic injury is illustrated by a 2011 survey of members of the American Association for the Surgery of Trauma. Members favored observation, not angiography, for grades 1 and 2 spleen injuries but showed no consensus on higher-grade injuries (J. Trauma 2011;70:1026-31).
A recent study of 1,275 patients treated for blunt splenic injury at four trauma centers that showed a significantly better chance of saving the spleen at hospitals with higher use of splenic artery embolization, especially in patients with higher-grade splenic injury (J. Trauma Acute Care Surg. 2013;75:69-74).
The current study excluded patients who died on arrival at the hospital, patients who were admitted more than 24 hours after injury, and patients who underwent splenectomy within 6 hours of admission (early splenectomy).
Dr. Zarzaur reported having no financial disclosures.
On Twitter @sherryboschert
AT THE AAST ANNUAL MEETING
Major finding: The likelihood of delayed splenectomy was 33% higher at centers without angiography and 49% higher at low-angiography centers, compared with high-angiography centers, but the differences were not statistically significant.
Data source: Retrospective analysis of data from the National Trauma Data Bank on 6,870 patients treated for blunt splenic injury at 267 hospitals.
Disclosures: Dr. Zarzaur reported having no financial disclosures.
Breast cancer hormone therapy may affect cognitive function
SAN FRANCISCO – Patients with breast cancer who received hormone therapy were over seven times more likely to show cognitive decline as were untreated patients after controlling for other factors, based on a prospective study of 81 patients.
Further, objective results on neuropsychological testing tended to back up patients’ complaints of cognitive difficulties.
Hormone therapy may be a risk factor for cognitive deficits, and interventional studies should be designed to focus on this group of patients, Dr. Hope S. Rugo and her associates recommended in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
The study collected neuropsychological test results and patient reports before treatment and at several points after starting hormone therapy (22 patients), chemotherapy (14), or chemotherapy followed by hormone therapy (33), and in a control group of 12 untreated patients.
Compared with baseline results, nearly 25% of patients had cognitive decline on neuropsychological testing after 5 months. (Among treated patients, this occurred 1 month after ending chemotherapy or 5 months after starting hormone therapy.) Nearly 35% had cognitive declines at 9 months of follow-up, and 30% had cognitive declines after 18 months.
"Decline in cognitive function is common in patients receiving adjuvant therapy for early-stage breast cancer," concluded Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco. "Ongoing hormone therapy appears to be a risk factor for worse cognitive function."
Other factors that did not predict cognitive decline in the multivariate analysis included age, education level, average estradiol level over time, and estimated verbal IQ at baseline.
Separate univariate conditional logistic regression analyses found that hormone therapy predicted cognitive decline with an odds ratio of 5, but chemotherapy, radiation therapy, average fatigue over time, and average depression over time were not predictive of cognitive decline at any point.
The study enrolled women aged 35-80 years with early-stage breast cancer. Those who underwent adjuvant therapy received 3-4 months of chemotherapy alone, 5 years of hormone therapy alone, or both.
A separate analysis in the same study looked at how well subjective patient reports correlated with objective measures on neuropsychological tests. Dr. Lara Heflin and her associates found significant cross-section correlations between patient-reported cognitive problems and psychological distress and fatigue.
After researchers controlled for the influence of depression and fatigue, however, significant relationships remained between patients’ perceived cognitive functioning and measurable cognitive decline from baseline (pretreatment) to the first follow-up. Patients whose scores indicated memory decline were more likely to perceive memory problems, and patients whose scores on letter fluency declined were more likely to perceive problems with verbal fluency.
"Patients who self-report cognitive problems may indeed be experiencing cognitive decline, and their self-report should not simply be attributed to fatigue or to psychological factors such as anxiety and depression," concluded Dr. Heflin, a visiting professor of psychology at New Mexico Highlands University, Las Vegas.
Patients in the study had no prior chemotherapy or central nervous system radiation and no history of major psychiatric illness, serious head injury, neurologic disease, drug or alcohol abuse, or significant medical illness. The median age was 54 years, and 78% of patients were white. Patient characteristics were similar between groups.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
The National Institutes of Health funded the study. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.
On Twitter @sherryboschert
While the relationship between chemotherapy and neurocognitive changes is increasingly well described, cognitive changes associated with hormone therapy for breast cancer has proven to be somewhat complex. Chemotherapy can confound this. There are questions about different reports of outcomes for different drugs, for selective estrogen-receptor modulators and aromatase inhibitors, as well as how menopausal status, prior oophorectomy, and hormone therapy all affect cognitive changes in women.
 |
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The important points of this study are that there are measurements at baseline, 1 month, and 18 months for a longitudinal picture. In addition, both comprehensive neuropsychological testing and patient-reported outcomes are available at each of those time points.
Previous studies have assessed these relationships, including a small study of memory impairment with anastrozole vs. tamoxifen in 31 patients treated for a minimum of 3 months. There was no difference between groups in depression, anxiety and fatigue, but researchers found that those on anastrozole had significantly poorer performance on learning and memory measures than those taking tamoxifen (Menopause 2007;14:995-8).
Another small substudy compared 94 patients enrolled in the ATAC (Arimidex, Tamoxifen Alone or in Combination) study to 35 noncancer controls. There were no differences in working memory, attention and visual memory, but those on endocrine therapy had poorer performance on tests of verbal memory and processing speed compared with controls.
The IBIS II (International Breast Cancer Intervention II) prevention study comparing anastrozole vs. placebo showed no overall difference in cognitive function with the addition of anastrozole. At 6 months, those on anastrozole had poorer memory, but this finding resolved by 24 months.
In a subset of 179 patients in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) phase III adjuvant study, comparing exemestane with tamoxifen then exemestane, there was little change from baseline to 1 year in all domains of cognitive function with the addition of exemestane.
A substudy done from the BIG 1-98 (Breast International Group 1-98) trial indicated significant improvement in cognitive function from year 5 of therapy to year 6 after cessation of hormone therapies. Interestingly, perceived cognition did not change in the patients.
This finding corroborates similar results from a prospective, longitudinal study of cognitive complaints and neuropsychological testing for verbal memory, psychomotor speed, and executive functioning in 189 patients who were beginning hormone therapy at the University of California, Los Angeles. (J. Natl. Cancer Inst. 2013;105:791-801).
While the relationship between chemotherapy and neurocognitive changes is increasingly well described, cognitive changes associated with hormone therapy for breast cancer has proven to be somewhat complex. Chemotherapy can confound this. There are questions about different reports of outcomes for different drugs, for selective estrogen-receptor modulators and aromatase inhibitors, as well as how menopausal status, prior oophorectomy, and hormone therapy all affect cognitive changes in women.
|
|
The important points of this study are that there are measurements at baseline, 1 month, and 18 months for a longitudinal picture. In addition, both comprehensive neuropsychological testing and patient-reported outcomes are available at each of those time points.
Previous studies have assessed these relationships, including a small study of memory impairment with anastrozole vs. tamoxifen in 31 patients treated for a minimum of 3 months. There was no difference between groups in depression, anxiety and fatigue, but researchers found that those on anastrozole had significantly poorer performance on learning and memory measures than those taking tamoxifen (Menopause 2007;14:995-8).
Another small substudy compared 94 patients enrolled in the ATAC (Arimidex, Tamoxifen Alone or in Combination) study to 35 noncancer controls. There were no differences in working memory, attention and visual memory, but those on endocrine therapy had poorer performance on tests of verbal memory and processing speed compared with controls.
The IBIS II (International Breast Cancer Intervention II) prevention study comparing anastrozole vs. placebo showed no overall difference in cognitive function with the addition of anastrozole. At 6 months, those on anastrozole had poorer memory, but this finding resolved by 24 months.
In a subset of 179 patients in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) phase III adjuvant study, comparing exemestane with tamoxifen then exemestane, there was little change from baseline to 1 year in all domains of cognitive function with the addition of exemestane.
A substudy done from the BIG 1-98 (Breast International Group 1-98) trial indicated significant improvement in cognitive function from year 5 of therapy to year 6 after cessation of hormone therapies. Interestingly, perceived cognition did not change in the patients.
This finding corroborates similar results from a prospective, longitudinal study of cognitive complaints and neuropsychological testing for verbal memory, psychomotor speed, and executive functioning in 189 patients who were beginning hormone therapy at the University of California, Los Angeles. (J. Natl. Cancer Inst. 2013;105:791-801).
While the relationship between chemotherapy and neurocognitive changes is increasingly well described, cognitive changes associated with hormone therapy for breast cancer has proven to be somewhat complex. Chemotherapy can confound this. There are questions about different reports of outcomes for different drugs, for selective estrogen-receptor modulators and aromatase inhibitors, as well as how menopausal status, prior oophorectomy, and hormone therapy all affect cognitive changes in women.
|
|
The important points of this study are that there are measurements at baseline, 1 month, and 18 months for a longitudinal picture. In addition, both comprehensive neuropsychological testing and patient-reported outcomes are available at each of those time points.
Previous studies have assessed these relationships, including a small study of memory impairment with anastrozole vs. tamoxifen in 31 patients treated for a minimum of 3 months. There was no difference between groups in depression, anxiety and fatigue, but researchers found that those on anastrozole had significantly poorer performance on learning and memory measures than those taking tamoxifen (Menopause 2007;14:995-8).
Another small substudy compared 94 patients enrolled in the ATAC (Arimidex, Tamoxifen Alone or in Combination) study to 35 noncancer controls. There were no differences in working memory, attention and visual memory, but those on endocrine therapy had poorer performance on tests of verbal memory and processing speed compared with controls.
The IBIS II (International Breast Cancer Intervention II) prevention study comparing anastrozole vs. placebo showed no overall difference in cognitive function with the addition of anastrozole. At 6 months, those on anastrozole had poorer memory, but this finding resolved by 24 months.
In a subset of 179 patients in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) phase III adjuvant study, comparing exemestane with tamoxifen then exemestane, there was little change from baseline to 1 year in all domains of cognitive function with the addition of exemestane.
A substudy done from the BIG 1-98 (Breast International Group 1-98) trial indicated significant improvement in cognitive function from year 5 of therapy to year 6 after cessation of hormone therapies. Interestingly, perceived cognition did not change in the patients.
This finding corroborates similar results from a prospective, longitudinal study of cognitive complaints and neuropsychological testing for verbal memory, psychomotor speed, and executive functioning in 189 patients who were beginning hormone therapy at the University of California, Los Angeles. (J. Natl. Cancer Inst. 2013;105:791-801).
SAN FRANCISCO – Patients with breast cancer who received hormone therapy were over seven times more likely to show cognitive decline as were untreated patients after controlling for other factors, based on a prospective study of 81 patients.
Further, objective results on neuropsychological testing tended to back up patients’ complaints of cognitive difficulties.
Hormone therapy may be a risk factor for cognitive deficits, and interventional studies should be designed to focus on this group of patients, Dr. Hope S. Rugo and her associates recommended in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
The study collected neuropsychological test results and patient reports before treatment and at several points after starting hormone therapy (22 patients), chemotherapy (14), or chemotherapy followed by hormone therapy (33), and in a control group of 12 untreated patients.
Compared with baseline results, nearly 25% of patients had cognitive decline on neuropsychological testing after 5 months. (Among treated patients, this occurred 1 month after ending chemotherapy or 5 months after starting hormone therapy.) Nearly 35% had cognitive declines at 9 months of follow-up, and 30% had cognitive declines after 18 months.
"Decline in cognitive function is common in patients receiving adjuvant therapy for early-stage breast cancer," concluded Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco. "Ongoing hormone therapy appears to be a risk factor for worse cognitive function."
Other factors that did not predict cognitive decline in the multivariate analysis included age, education level, average estradiol level over time, and estimated verbal IQ at baseline.
Separate univariate conditional logistic regression analyses found that hormone therapy predicted cognitive decline with an odds ratio of 5, but chemotherapy, radiation therapy, average fatigue over time, and average depression over time were not predictive of cognitive decline at any point.
The study enrolled women aged 35-80 years with early-stage breast cancer. Those who underwent adjuvant therapy received 3-4 months of chemotherapy alone, 5 years of hormone therapy alone, or both.
A separate analysis in the same study looked at how well subjective patient reports correlated with objective measures on neuropsychological tests. Dr. Lara Heflin and her associates found significant cross-section correlations between patient-reported cognitive problems and psychological distress and fatigue.
After researchers controlled for the influence of depression and fatigue, however, significant relationships remained between patients’ perceived cognitive functioning and measurable cognitive decline from baseline (pretreatment) to the first follow-up. Patients whose scores indicated memory decline were more likely to perceive memory problems, and patients whose scores on letter fluency declined were more likely to perceive problems with verbal fluency.
"Patients who self-report cognitive problems may indeed be experiencing cognitive decline, and their self-report should not simply be attributed to fatigue or to psychological factors such as anxiety and depression," concluded Dr. Heflin, a visiting professor of psychology at New Mexico Highlands University, Las Vegas.
Patients in the study had no prior chemotherapy or central nervous system radiation and no history of major psychiatric illness, serious head injury, neurologic disease, drug or alcohol abuse, or significant medical illness. The median age was 54 years, and 78% of patients were white. Patient characteristics were similar between groups.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
The National Institutes of Health funded the study. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.
On Twitter @sherryboschert
SAN FRANCISCO – Patients with breast cancer who received hormone therapy were over seven times more likely to show cognitive decline as were untreated patients after controlling for other factors, based on a prospective study of 81 patients.
Further, objective results on neuropsychological testing tended to back up patients’ complaints of cognitive difficulties.
Hormone therapy may be a risk factor for cognitive deficits, and interventional studies should be designed to focus on this group of patients, Dr. Hope S. Rugo and her associates recommended in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
The study collected neuropsychological test results and patient reports before treatment and at several points after starting hormone therapy (22 patients), chemotherapy (14), or chemotherapy followed by hormone therapy (33), and in a control group of 12 untreated patients.
Compared with baseline results, nearly 25% of patients had cognitive decline on neuropsychological testing after 5 months. (Among treated patients, this occurred 1 month after ending chemotherapy or 5 months after starting hormone therapy.) Nearly 35% had cognitive declines at 9 months of follow-up, and 30% had cognitive declines after 18 months.
"Decline in cognitive function is common in patients receiving adjuvant therapy for early-stage breast cancer," concluded Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco. "Ongoing hormone therapy appears to be a risk factor for worse cognitive function."
Other factors that did not predict cognitive decline in the multivariate analysis included age, education level, average estradiol level over time, and estimated verbal IQ at baseline.
Separate univariate conditional logistic regression analyses found that hormone therapy predicted cognitive decline with an odds ratio of 5, but chemotherapy, radiation therapy, average fatigue over time, and average depression over time were not predictive of cognitive decline at any point.
The study enrolled women aged 35-80 years with early-stage breast cancer. Those who underwent adjuvant therapy received 3-4 months of chemotherapy alone, 5 years of hormone therapy alone, or both.
A separate analysis in the same study looked at how well subjective patient reports correlated with objective measures on neuropsychological tests. Dr. Lara Heflin and her associates found significant cross-section correlations between patient-reported cognitive problems and psychological distress and fatigue.
After researchers controlled for the influence of depression and fatigue, however, significant relationships remained between patients’ perceived cognitive functioning and measurable cognitive decline from baseline (pretreatment) to the first follow-up. Patients whose scores indicated memory decline were more likely to perceive memory problems, and patients whose scores on letter fluency declined were more likely to perceive problems with verbal fluency.
"Patients who self-report cognitive problems may indeed be experiencing cognitive decline, and their self-report should not simply be attributed to fatigue or to psychological factors such as anxiety and depression," concluded Dr. Heflin, a visiting professor of psychology at New Mexico Highlands University, Las Vegas.
Patients in the study had no prior chemotherapy or central nervous system radiation and no history of major psychiatric illness, serious head injury, neurologic disease, drug or alcohol abuse, or significant medical illness. The median age was 54 years, and 78% of patients were white. Patient characteristics were similar between groups.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
The National Institutes of Health funded the study. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.
On Twitter @sherryboschert
AT THE ASCO BREAST CANCER SYMPOSIUM
Major finding: The odds of any decline in cognitive function were significantly higher in patients on hormone therapy (OR, 7.7), compared with untreated patients in a multivariate conditional logistic regression analysis.
Data source: Prospective longitudinal study of 81 patients with breast cancer treated with hormone therapy (22 patients), chemotherapy (14), chemotherapy followed by hormone therapy (33), or no therapy (12).
Disclosures: NIH funded the study. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.
Inpatient intervention changed patients’ attitudes about violence
SAN FRANCISCO – An inpatient intervention that used gunshot or stab wounds as "teachable moments" significantly improved some attitudes about violence in a randomized study of 40 hospitalized trauma patients.
The prospective pilot study administered the Attitudes Toward Guns and Violence Questionnaire (AGVQ) before and after the intervention or usual care for patients treated at Temple University Hospital, Philadelphia, from January to June 2012. Their general proclivity toward violence (the overall AGVQ score) decreased by 20% in the intervention group (from a mean score of 15 to 12.1) and held steady in the control group (scores of 11.5 and 11.3).
Two subscales of the AGVQ also produced significant attitudinal changes after the intervention, a four-part program called Turning Point, Dr. Catherine E. Loveland-Jones and her associates reported at the annual meeting of the American Association for the Surgery of Trauma.
Patients’ comfort with aggression (or acceptance of violence as a part of everyday life) decreased from a mean score of 4.2 to 2.8 after the intervention (a 33% reduction) compared with scores of 2.9 and 2.8, respectively, in the control group.
The greatest change was seen in scores for aggressive response to shame. Patients in the intervention group showed a 44% reduction in their sensitivity to disrespect from others and the belief that violence is the best means for preserving one’s damaged self-esteem, said Dr. Loveland-Jones of Temple University. Their mean scores decreased from 3.6 to 2 after the intervention, compared with scores of 3.1 and 2.6 in the control group.
"We believe that attitude change is fundamental and really the first step to behavior change," she said. The ongoing study is nearing its goal of enrolling 80 patients.
A separate program at her institution to prevent violence in youth also had its greatest impact on attitudes about shame and violence. The findings are encouraging because reaction to shame is thought to be a driver of violence in the study’s population, she said.
All patients in the study received the usual social services care offered at the urban Level 1 trauma center to victims of gunshot and stab wounds, consisting of team care from a trauma outreach coordinator, a case manager, and a social worker. The 21 patients in the Turning Point group also watched a video of their resuscitation in the trauma bay and a reality-based movie about violence. They met with a gunshot wound survivor, were introduced to an outpatient case manager, and received a psychiatric evaluation if the patient or a clinician requested one.
"I think the most important part of our program is our referral to outpatient services," Dr. Loveland-Jones said. Previous data suggest that "meeting mental health needs and finding employment for patients are the most important," and that moderate- to high-intensity case management in the first 3 months after the trauma helps achieve that.
The study enrolled English-speaking adults with gunshot or stab wounds who had a Glasgow Coma Score of 15. The cohort "overwhelmingly" consisted of black males in their 20s, she said. In general, more than half of gunshot victims in Philadelphia are young, she added.
The Turning Point program costs $50,000 per year and subcontracts with an established community group for the outpatient case management.
Two subscales of the AGVQ did not change significantly in either group. Scores were lowest for reported levels of gun-related excitement, "suggesting that guns are viewed as necessary and commonplace rather than exciting," she said. The AGVQ scores before and after the intervention were 0.1 and 0.5 in the control group, respectively, and remained at 0.3 in the Turning Point group.
Scores were highest for feelings of gun-related power and safety, "suggesting that there is a very strong view in our community that guns are a necessary means for preserving personal safety," she said. The AGVQ scores before and after the intervention were 5 and 5.2 in the control group and 6 and 6.4 in the Turning Point group, respectively.
The study excluded 119 (75%) of 159 potential participants, primarily patients who stayed in the hospital less than 48 hours (69%). A total of 9% of patients refused to participate. Other reasons for exclusion were police custody (7%), devastating neurologic injury (4%), severe psychiatric disorder (2%), and unknown reasons (2%). Investigators also excluded 3% who were non-English speakers, 2% who left the hospital against medical advice, and 2% who planned to relocate after discharge.
Patients in the Turning Point group were significantly more likely to be alcohol abusers (26%), compared with the control group (14%), and were significantly younger – an average of 22 years vs. 31 years in the control group.
The investigators designed the Turning Point program components based on a prior survey that asked similar patients what would be useful. Unlike tactics in some programs such as Scared Straight that "don’t work," Turning Point’s videos are not meant to scare patients but to provide a platform for discussing the gravity of their injuries and how much they value their lives, she said.
"I applaud the compassion and insight of those individuals who conducted and participated in Turning Point, which is much needed and long overdue. It just goes to show that you can use almost any situation as a teachable moment; and when an individual is faced with his own mortality, he is likely to be all ears," remarked Dr. A. Maria Hester, a hospitalist with Baltimore-Washington Medical Center. Dr. Hester writes the "Teachable Moments" blog for Hospitalist News.
Dr. Loveland-Jones reported having no financial disclosures.
On Twitter @sherryboschert
It was 13 years ago now that Surgeon General C. Everett Koop recognized violent injury as a public health issue. His statement, and the concept of violence prevention implicit in his statement, has served as a foundation for the development of hospital-based violence prevention programs nationwide.
Fast-forward to 2013 and the violence prevention programs that have been recognized as an integral part of many of our trauma centers, championed by surgeons, emergency medicine physicians, trauma nurse coordinators, community leaders, and hospital foundations and even administrations. Today, the National Network of Hospital-Based Violence Intervention Programs boasts 22 full members and 12 emerging programs (with more on the horizon and other groups such as Turning Points) to be admired.
The mission of the National Network has been to establish best practices for violence prevention programs and to provide some technical support to fledgling programs so that groups wanting to establish programs don’t have to start from scratch or reinvent the wheel. Integral to the development of best practices is quantitative scientific studies demonstrating feasibility, utility, interim and long-term efficacy, and perhaps fidelity.
As the authors of this paper recognized, several quantitative studies have demonstrated positive results, with ultimate reduction in injury recidivism. Just as vital, however, to best understand the components of success or failure are programmatic analyses. The authors provide us with one such study, and I applaud them for their efforts. Dr. Loveland-Jones and her colleagues representing Temple’s violence prevention program Turning Point did a very nice job in providing us with appropriate context.
I also applaud them for conducting a randomized controlled trial in this field, as many of us know it’s quite difficult given the characteristic lack of equipoise, especially in our communities that are particularly affected by violence. I would just caution the authors but also encourage them to continue with the psychiatric evaluation. That is so important in our patient population.
It is only by these programmatic studies and the multi-institutional documentation that we’re engaged in now that the successes and failures can be identified so we can move to best practices for violence prevention as standard of care in many of our trauma centers.
Dr. Rochelle Dicker is director of the San Francisco Injury Center at San Francisco General Hospital. These are excerpts of her remarks as the discussant of the study at the meeting.
It was 13 years ago now that Surgeon General C. Everett Koop recognized violent injury as a public health issue. His statement, and the concept of violence prevention implicit in his statement, has served as a foundation for the development of hospital-based violence prevention programs nationwide.
Fast-forward to 2013 and the violence prevention programs that have been recognized as an integral part of many of our trauma centers, championed by surgeons, emergency medicine physicians, trauma nurse coordinators, community leaders, and hospital foundations and even administrations. Today, the National Network of Hospital-Based Violence Intervention Programs boasts 22 full members and 12 emerging programs (with more on the horizon and other groups such as Turning Points) to be admired.
The mission of the National Network has been to establish best practices for violence prevention programs and to provide some technical support to fledgling programs so that groups wanting to establish programs don’t have to start from scratch or reinvent the wheel. Integral to the development of best practices is quantitative scientific studies demonstrating feasibility, utility, interim and long-term efficacy, and perhaps fidelity.
As the authors of this paper recognized, several quantitative studies have demonstrated positive results, with ultimate reduction in injury recidivism. Just as vital, however, to best understand the components of success or failure are programmatic analyses. The authors provide us with one such study, and I applaud them for their efforts. Dr. Loveland-Jones and her colleagues representing Temple’s violence prevention program Turning Point did a very nice job in providing us with appropriate context.
I also applaud them for conducting a randomized controlled trial in this field, as many of us know it’s quite difficult given the characteristic lack of equipoise, especially in our communities that are particularly affected by violence. I would just caution the authors but also encourage them to continue with the psychiatric evaluation. That is so important in our patient population.
It is only by these programmatic studies and the multi-institutional documentation that we’re engaged in now that the successes and failures can be identified so we can move to best practices for violence prevention as standard of care in many of our trauma centers.
Dr. Rochelle Dicker is director of the San Francisco Injury Center at San Francisco General Hospital. These are excerpts of her remarks as the discussant of the study at the meeting.
It was 13 years ago now that Surgeon General C. Everett Koop recognized violent injury as a public health issue. His statement, and the concept of violence prevention implicit in his statement, has served as a foundation for the development of hospital-based violence prevention programs nationwide.
Fast-forward to 2013 and the violence prevention programs that have been recognized as an integral part of many of our trauma centers, championed by surgeons, emergency medicine physicians, trauma nurse coordinators, community leaders, and hospital foundations and even administrations. Today, the National Network of Hospital-Based Violence Intervention Programs boasts 22 full members and 12 emerging programs (with more on the horizon and other groups such as Turning Points) to be admired.
The mission of the National Network has been to establish best practices for violence prevention programs and to provide some technical support to fledgling programs so that groups wanting to establish programs don’t have to start from scratch or reinvent the wheel. Integral to the development of best practices is quantitative scientific studies demonstrating feasibility, utility, interim and long-term efficacy, and perhaps fidelity.
As the authors of this paper recognized, several quantitative studies have demonstrated positive results, with ultimate reduction in injury recidivism. Just as vital, however, to best understand the components of success or failure are programmatic analyses. The authors provide us with one such study, and I applaud them for their efforts. Dr. Loveland-Jones and her colleagues representing Temple’s violence prevention program Turning Point did a very nice job in providing us with appropriate context.
I also applaud them for conducting a randomized controlled trial in this field, as many of us know it’s quite difficult given the characteristic lack of equipoise, especially in our communities that are particularly affected by violence. I would just caution the authors but also encourage them to continue with the psychiatric evaluation. That is so important in our patient population.
It is only by these programmatic studies and the multi-institutional documentation that we’re engaged in now that the successes and failures can be identified so we can move to best practices for violence prevention as standard of care in many of our trauma centers.
Dr. Rochelle Dicker is director of the San Francisco Injury Center at San Francisco General Hospital. These are excerpts of her remarks as the discussant of the study at the meeting.
SAN FRANCISCO – An inpatient intervention that used gunshot or stab wounds as "teachable moments" significantly improved some attitudes about violence in a randomized study of 40 hospitalized trauma patients.
The prospective pilot study administered the Attitudes Toward Guns and Violence Questionnaire (AGVQ) before and after the intervention or usual care for patients treated at Temple University Hospital, Philadelphia, from January to June 2012. Their general proclivity toward violence (the overall AGVQ score) decreased by 20% in the intervention group (from a mean score of 15 to 12.1) and held steady in the control group (scores of 11.5 and 11.3).
Two subscales of the AGVQ also produced significant attitudinal changes after the intervention, a four-part program called Turning Point, Dr. Catherine E. Loveland-Jones and her associates reported at the annual meeting of the American Association for the Surgery of Trauma.
Patients’ comfort with aggression (or acceptance of violence as a part of everyday life) decreased from a mean score of 4.2 to 2.8 after the intervention (a 33% reduction) compared with scores of 2.9 and 2.8, respectively, in the control group.
The greatest change was seen in scores for aggressive response to shame. Patients in the intervention group showed a 44% reduction in their sensitivity to disrespect from others and the belief that violence is the best means for preserving one’s damaged self-esteem, said Dr. Loveland-Jones of Temple University. Their mean scores decreased from 3.6 to 2 after the intervention, compared with scores of 3.1 and 2.6 in the control group.
"We believe that attitude change is fundamental and really the first step to behavior change," she said. The ongoing study is nearing its goal of enrolling 80 patients.
A separate program at her institution to prevent violence in youth also had its greatest impact on attitudes about shame and violence. The findings are encouraging because reaction to shame is thought to be a driver of violence in the study’s population, she said.
All patients in the study received the usual social services care offered at the urban Level 1 trauma center to victims of gunshot and stab wounds, consisting of team care from a trauma outreach coordinator, a case manager, and a social worker. The 21 patients in the Turning Point group also watched a video of their resuscitation in the trauma bay and a reality-based movie about violence. They met with a gunshot wound survivor, were introduced to an outpatient case manager, and received a psychiatric evaluation if the patient or a clinician requested one.
"I think the most important part of our program is our referral to outpatient services," Dr. Loveland-Jones said. Previous data suggest that "meeting mental health needs and finding employment for patients are the most important," and that moderate- to high-intensity case management in the first 3 months after the trauma helps achieve that.
The study enrolled English-speaking adults with gunshot or stab wounds who had a Glasgow Coma Score of 15. The cohort "overwhelmingly" consisted of black males in their 20s, she said. In general, more than half of gunshot victims in Philadelphia are young, she added.
The Turning Point program costs $50,000 per year and subcontracts with an established community group for the outpatient case management.
Two subscales of the AGVQ did not change significantly in either group. Scores were lowest for reported levels of gun-related excitement, "suggesting that guns are viewed as necessary and commonplace rather than exciting," she said. The AGVQ scores before and after the intervention were 0.1 and 0.5 in the control group, respectively, and remained at 0.3 in the Turning Point group.
Scores were highest for feelings of gun-related power and safety, "suggesting that there is a very strong view in our community that guns are a necessary means for preserving personal safety," she said. The AGVQ scores before and after the intervention were 5 and 5.2 in the control group and 6 and 6.4 in the Turning Point group, respectively.
The study excluded 119 (75%) of 159 potential participants, primarily patients who stayed in the hospital less than 48 hours (69%). A total of 9% of patients refused to participate. Other reasons for exclusion were police custody (7%), devastating neurologic injury (4%), severe psychiatric disorder (2%), and unknown reasons (2%). Investigators also excluded 3% who were non-English speakers, 2% who left the hospital against medical advice, and 2% who planned to relocate after discharge.
Patients in the Turning Point group were significantly more likely to be alcohol abusers (26%), compared with the control group (14%), and were significantly younger – an average of 22 years vs. 31 years in the control group.
The investigators designed the Turning Point program components based on a prior survey that asked similar patients what would be useful. Unlike tactics in some programs such as Scared Straight that "don’t work," Turning Point’s videos are not meant to scare patients but to provide a platform for discussing the gravity of their injuries and how much they value their lives, she said.
"I applaud the compassion and insight of those individuals who conducted and participated in Turning Point, which is much needed and long overdue. It just goes to show that you can use almost any situation as a teachable moment; and when an individual is faced with his own mortality, he is likely to be all ears," remarked Dr. A. Maria Hester, a hospitalist with Baltimore-Washington Medical Center. Dr. Hester writes the "Teachable Moments" blog for Hospitalist News.
Dr. Loveland-Jones reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – An inpatient intervention that used gunshot or stab wounds as "teachable moments" significantly improved some attitudes about violence in a randomized study of 40 hospitalized trauma patients.
The prospective pilot study administered the Attitudes Toward Guns and Violence Questionnaire (AGVQ) before and after the intervention or usual care for patients treated at Temple University Hospital, Philadelphia, from January to June 2012. Their general proclivity toward violence (the overall AGVQ score) decreased by 20% in the intervention group (from a mean score of 15 to 12.1) and held steady in the control group (scores of 11.5 and 11.3).
Two subscales of the AGVQ also produced significant attitudinal changes after the intervention, a four-part program called Turning Point, Dr. Catherine E. Loveland-Jones and her associates reported at the annual meeting of the American Association for the Surgery of Trauma.
Patients’ comfort with aggression (or acceptance of violence as a part of everyday life) decreased from a mean score of 4.2 to 2.8 after the intervention (a 33% reduction) compared with scores of 2.9 and 2.8, respectively, in the control group.
The greatest change was seen in scores for aggressive response to shame. Patients in the intervention group showed a 44% reduction in their sensitivity to disrespect from others and the belief that violence is the best means for preserving one’s damaged self-esteem, said Dr. Loveland-Jones of Temple University. Their mean scores decreased from 3.6 to 2 after the intervention, compared with scores of 3.1 and 2.6 in the control group.
"We believe that attitude change is fundamental and really the first step to behavior change," she said. The ongoing study is nearing its goal of enrolling 80 patients.
A separate program at her institution to prevent violence in youth also had its greatest impact on attitudes about shame and violence. The findings are encouraging because reaction to shame is thought to be a driver of violence in the study’s population, she said.
All patients in the study received the usual social services care offered at the urban Level 1 trauma center to victims of gunshot and stab wounds, consisting of team care from a trauma outreach coordinator, a case manager, and a social worker. The 21 patients in the Turning Point group also watched a video of their resuscitation in the trauma bay and a reality-based movie about violence. They met with a gunshot wound survivor, were introduced to an outpatient case manager, and received a psychiatric evaluation if the patient or a clinician requested one.
"I think the most important part of our program is our referral to outpatient services," Dr. Loveland-Jones said. Previous data suggest that "meeting mental health needs and finding employment for patients are the most important," and that moderate- to high-intensity case management in the first 3 months after the trauma helps achieve that.
The study enrolled English-speaking adults with gunshot or stab wounds who had a Glasgow Coma Score of 15. The cohort "overwhelmingly" consisted of black males in their 20s, she said. In general, more than half of gunshot victims in Philadelphia are young, she added.
The Turning Point program costs $50,000 per year and subcontracts with an established community group for the outpatient case management.
Two subscales of the AGVQ did not change significantly in either group. Scores were lowest for reported levels of gun-related excitement, "suggesting that guns are viewed as necessary and commonplace rather than exciting," she said. The AGVQ scores before and after the intervention were 0.1 and 0.5 in the control group, respectively, and remained at 0.3 in the Turning Point group.
Scores were highest for feelings of gun-related power and safety, "suggesting that there is a very strong view in our community that guns are a necessary means for preserving personal safety," she said. The AGVQ scores before and after the intervention were 5 and 5.2 in the control group and 6 and 6.4 in the Turning Point group, respectively.
The study excluded 119 (75%) of 159 potential participants, primarily patients who stayed in the hospital less than 48 hours (69%). A total of 9% of patients refused to participate. Other reasons for exclusion were police custody (7%), devastating neurologic injury (4%), severe psychiatric disorder (2%), and unknown reasons (2%). Investigators also excluded 3% who were non-English speakers, 2% who left the hospital against medical advice, and 2% who planned to relocate after discharge.
Patients in the Turning Point group were significantly more likely to be alcohol abusers (26%), compared with the control group (14%), and were significantly younger – an average of 22 years vs. 31 years in the control group.
The investigators designed the Turning Point program components based on a prior survey that asked similar patients what would be useful. Unlike tactics in some programs such as Scared Straight that "don’t work," Turning Point’s videos are not meant to scare patients but to provide a platform for discussing the gravity of their injuries and how much they value their lives, she said.
"I applaud the compassion and insight of those individuals who conducted and participated in Turning Point, which is much needed and long overdue. It just goes to show that you can use almost any situation as a teachable moment; and when an individual is faced with his own mortality, he is likely to be all ears," remarked Dr. A. Maria Hester, a hospitalist with Baltimore-Washington Medical Center. Dr. Hester writes the "Teachable Moments" blog for Hospitalist News.
Dr. Loveland-Jones reported having no financial disclosures.
On Twitter @sherryboschert
AT THE AAST ANNUAL MEETING
Major finding: General proclivity toward violence decreased 20%, comfort with aggression decreased 33%, and the inclination to respond aggressively to shame decreased 44% in the intervention group, with no significant changes in the control group.
Data source: A pilot randomized, controlled trial of 40 hospitalized victims of gunshot or stab wounds at one trauma center.
Disclosures: Dr. Loveland-Jones reported having no financial disclosures.
Outpatient laparoscopic appendectomy found safe, cost saving
SAN FRANCISCO – Implementing an outpatient laparoscopic appendectomy protocol for uncomplicated appendicitis allowed 88% of 345 cases at one institution to be performed without hospitalizing the patient overnight.
The outpatients went home an average of 171 minutes after completion of the surgery.
Forty patients were admitted (12%) because of pre-existing comorbidities in 15 patients, postoperative morbidity in 6, and a lack of transportation or assistance for 19, Dr. Richard C. Frazee and his associates reported.
Only 4 of the 305 patients who underwent the procedure as outpatients were admitted after going home, for an overall outpatient success rate of 87%, he said at the annual meeting of the American Association for the Surgery of Trauma. Reasons for readmission included fever, nausea and vomiting, partial small bowel obstruction, or deep vein thrombosis.
Morbidity affected 7% of patients in the form of urinary retention, wound infection, operative enterotomy, cecal serosal injury, deep vein thrombosis, or exacerbation of chronic obstructive pulmonary disease. One laparoscopic appendectomy was converted to open surgery; none of the patients died.
This is not the first time Dr. Frazee has presented his institution’s experience with the outpatient laparoscopic appendectomy protocol; he shared similar findings from an earlier series at the same meeting a few years ago. In an interview, he expressed some frustration that more hospitals haven’t adopted similar protocols.
By his rough calculation, 20% of all laparoscopic uncomplicated appendectomies performed in the United States each year cause perforations requiring hospitalization and 80% of the rest are successful outpatient procedures. That means 242,760 patients each year would not be hospitalized overnight for this surgery. Separate data show that the average U.S. length of hospitalization for laparoscopic appendectomy is 2 days, at an average cost of $1,900 per day. Nationwide adoption of an outpatient protocol potentially could avoid over $921 million in annual costs.
"It is time for us to create a change in the standard of care for uncomplicated appendicitis," said Dr. Frazee, chief of acute care surgery at Scott & White Healthcare in Temple, Tex.
His interest in the subject started when his son, an otherwise healthy young adult, complained about having to stay in the hospital after a laparoscopic appendectomy. Dr. Frazee conducted a review of 119 laparoscopic appendectomies at his institution and found that 35% of patients went home the same day, 61% were admitted for a day, and the few others were hospitalized longer. Morbidity was seen in 8%.
He and his colleagues developed an outpatient protocol in July 2010, under which patients undergoing uncomplicated laparoscopic appendectomies would not be admitted unless they were pregnant or younger than 17 years, or if a perforated or gangrenous appendicitis was discovered during the surgery. To qualify for same-day discharge, outpatients had to be able to tolerate intake of liquids, ambulate, urinate, and have adequate respiratory effort. They also had to be hemodynamically stable, have pain controlled with oral analgesics, have nausea and vomiting controlled, show no alteration in mental status from baseline, have the approval of their physician, and have appropriate supervision and assistance at home.
An initial review compared 116 patients treated under the protocol in 2010-2011 with historical controls and found a significant reduction in length of stay without increased morbidity. Under the protocol, 85% of patients were outpatients, compared with 35% in the control group. Postoperative morbidity affected 5% in the protocol group and 8% in the control group, and no patients were readmitted (Am. Surg. 2012;215:101-5).
Since then, the outpatient protocol has been the standard of care at his institution. The current report covers 166 men and 179 women treated under the protocol from July 2010 through December 2012. They had a mean age of 35 years and a mean body mass index of 31 kg/m2. Thirty-two percent had a history of prior abdominal surgery. Comorbidities at baseline included hypertension in 29%, diabetes in 11%, coronary artery disease in 4%, and chronic obstructive pulmonary disease in 1%.
Outpatients were sent home from the day surgery unit or the post–anesthetic care unit. Thirty percent were dismissed between 6 a.m. and noon, 15% went home between noon and 6 p.m., 25% were dismissed between 6 p.m. and midnight, and 30% went home between midnight and 6 a.m.
The investigators now are conducting a follow-up study to assess patient satisfaction with the protocol. "Our impression is that they like going home the same day," but a study will confirm whether this is true or not, he said.
Dr. Frazee reported having no financial disclosures.
This is a well-written paper that continues a series of contributions from the authors addressing management of acute appendicitis. A 1994 paper from the authors prospectively compared laparoscopic with open appendectomy. In 2012, the authors reported and described their protocol for outpatient management of laparoscopic appendectomy, comparing 116 patients with a matched historical cohort group. This paper is an update of the 2012 paper and now includes 345 patients.
They assume that their patients are at home, happy, and doing well after discharge. They may not be. The conclusions would be more valid if patients had completed a questionnaire that stated that they were home and doing well, as other authors have done in studying this disease.
The report provides mean times from the emergency department to the operating room and from completion of surgery to discharge. Median times would be helpful to know.
I congratulate them on a well-presented and well-written paper.
Dr. Andrew Peitzman is professor of surgery and chief of general surgery and of trauma/surgical critical care at the University of Pittsburgh. He gave these comments as the discussant of Dr. Frazee’s study at the meeting.
This is a well-written paper that continues a series of contributions from the authors addressing management of acute appendicitis. A 1994 paper from the authors prospectively compared laparoscopic with open appendectomy. In 2012, the authors reported and described their protocol for outpatient management of laparoscopic appendectomy, comparing 116 patients with a matched historical cohort group. This paper is an update of the 2012 paper and now includes 345 patients.
They assume that their patients are at home, happy, and doing well after discharge. They may not be. The conclusions would be more valid if patients had completed a questionnaire that stated that they were home and doing well, as other authors have done in studying this disease.
The report provides mean times from the emergency department to the operating room and from completion of surgery to discharge. Median times would be helpful to know.
I congratulate them on a well-presented and well-written paper.
Dr. Andrew Peitzman is professor of surgery and chief of general surgery and of trauma/surgical critical care at the University of Pittsburgh. He gave these comments as the discussant of Dr. Frazee’s study at the meeting.
This is a well-written paper that continues a series of contributions from the authors addressing management of acute appendicitis. A 1994 paper from the authors prospectively compared laparoscopic with open appendectomy. In 2012, the authors reported and described their protocol for outpatient management of laparoscopic appendectomy, comparing 116 patients with a matched historical cohort group. This paper is an update of the 2012 paper and now includes 345 patients.
They assume that their patients are at home, happy, and doing well after discharge. They may not be. The conclusions would be more valid if patients had completed a questionnaire that stated that they were home and doing well, as other authors have done in studying this disease.
The report provides mean times from the emergency department to the operating room and from completion of surgery to discharge. Median times would be helpful to know.
I congratulate them on a well-presented and well-written paper.
Dr. Andrew Peitzman is professor of surgery and chief of general surgery and of trauma/surgical critical care at the University of Pittsburgh. He gave these comments as the discussant of Dr. Frazee’s study at the meeting.
SAN FRANCISCO – Implementing an outpatient laparoscopic appendectomy protocol for uncomplicated appendicitis allowed 88% of 345 cases at one institution to be performed without hospitalizing the patient overnight.
The outpatients went home an average of 171 minutes after completion of the surgery.
Forty patients were admitted (12%) because of pre-existing comorbidities in 15 patients, postoperative morbidity in 6, and a lack of transportation or assistance for 19, Dr. Richard C. Frazee and his associates reported.
Only 4 of the 305 patients who underwent the procedure as outpatients were admitted after going home, for an overall outpatient success rate of 87%, he said at the annual meeting of the American Association for the Surgery of Trauma. Reasons for readmission included fever, nausea and vomiting, partial small bowel obstruction, or deep vein thrombosis.
Morbidity affected 7% of patients in the form of urinary retention, wound infection, operative enterotomy, cecal serosal injury, deep vein thrombosis, or exacerbation of chronic obstructive pulmonary disease. One laparoscopic appendectomy was converted to open surgery; none of the patients died.
This is not the first time Dr. Frazee has presented his institution’s experience with the outpatient laparoscopic appendectomy protocol; he shared similar findings from an earlier series at the same meeting a few years ago. In an interview, he expressed some frustration that more hospitals haven’t adopted similar protocols.
By his rough calculation, 20% of all laparoscopic uncomplicated appendectomies performed in the United States each year cause perforations requiring hospitalization and 80% of the rest are successful outpatient procedures. That means 242,760 patients each year would not be hospitalized overnight for this surgery. Separate data show that the average U.S. length of hospitalization for laparoscopic appendectomy is 2 days, at an average cost of $1,900 per day. Nationwide adoption of an outpatient protocol potentially could avoid over $921 million in annual costs.
"It is time for us to create a change in the standard of care for uncomplicated appendicitis," said Dr. Frazee, chief of acute care surgery at Scott & White Healthcare in Temple, Tex.
His interest in the subject started when his son, an otherwise healthy young adult, complained about having to stay in the hospital after a laparoscopic appendectomy. Dr. Frazee conducted a review of 119 laparoscopic appendectomies at his institution and found that 35% of patients went home the same day, 61% were admitted for a day, and the few others were hospitalized longer. Morbidity was seen in 8%.
He and his colleagues developed an outpatient protocol in July 2010, under which patients undergoing uncomplicated laparoscopic appendectomies would not be admitted unless they were pregnant or younger than 17 years, or if a perforated or gangrenous appendicitis was discovered during the surgery. To qualify for same-day discharge, outpatients had to be able to tolerate intake of liquids, ambulate, urinate, and have adequate respiratory effort. They also had to be hemodynamically stable, have pain controlled with oral analgesics, have nausea and vomiting controlled, show no alteration in mental status from baseline, have the approval of their physician, and have appropriate supervision and assistance at home.
An initial review compared 116 patients treated under the protocol in 2010-2011 with historical controls and found a significant reduction in length of stay without increased morbidity. Under the protocol, 85% of patients were outpatients, compared with 35% in the control group. Postoperative morbidity affected 5% in the protocol group and 8% in the control group, and no patients were readmitted (Am. Surg. 2012;215:101-5).
Since then, the outpatient protocol has been the standard of care at his institution. The current report covers 166 men and 179 women treated under the protocol from July 2010 through December 2012. They had a mean age of 35 years and a mean body mass index of 31 kg/m2. Thirty-two percent had a history of prior abdominal surgery. Comorbidities at baseline included hypertension in 29%, diabetes in 11%, coronary artery disease in 4%, and chronic obstructive pulmonary disease in 1%.
Outpatients were sent home from the day surgery unit or the post–anesthetic care unit. Thirty percent were dismissed between 6 a.m. and noon, 15% went home between noon and 6 p.m., 25% were dismissed between 6 p.m. and midnight, and 30% went home between midnight and 6 a.m.
The investigators now are conducting a follow-up study to assess patient satisfaction with the protocol. "Our impression is that they like going home the same day," but a study will confirm whether this is true or not, he said.
Dr. Frazee reported having no financial disclosures.
SAN FRANCISCO – Implementing an outpatient laparoscopic appendectomy protocol for uncomplicated appendicitis allowed 88% of 345 cases at one institution to be performed without hospitalizing the patient overnight.
The outpatients went home an average of 171 minutes after completion of the surgery.
Forty patients were admitted (12%) because of pre-existing comorbidities in 15 patients, postoperative morbidity in 6, and a lack of transportation or assistance for 19, Dr. Richard C. Frazee and his associates reported.
Only 4 of the 305 patients who underwent the procedure as outpatients were admitted after going home, for an overall outpatient success rate of 87%, he said at the annual meeting of the American Association for the Surgery of Trauma. Reasons for readmission included fever, nausea and vomiting, partial small bowel obstruction, or deep vein thrombosis.
Morbidity affected 7% of patients in the form of urinary retention, wound infection, operative enterotomy, cecal serosal injury, deep vein thrombosis, or exacerbation of chronic obstructive pulmonary disease. One laparoscopic appendectomy was converted to open surgery; none of the patients died.
This is not the first time Dr. Frazee has presented his institution’s experience with the outpatient laparoscopic appendectomy protocol; he shared similar findings from an earlier series at the same meeting a few years ago. In an interview, he expressed some frustration that more hospitals haven’t adopted similar protocols.
By his rough calculation, 20% of all laparoscopic uncomplicated appendectomies performed in the United States each year cause perforations requiring hospitalization and 80% of the rest are successful outpatient procedures. That means 242,760 patients each year would not be hospitalized overnight for this surgery. Separate data show that the average U.S. length of hospitalization for laparoscopic appendectomy is 2 days, at an average cost of $1,900 per day. Nationwide adoption of an outpatient protocol potentially could avoid over $921 million in annual costs.
"It is time for us to create a change in the standard of care for uncomplicated appendicitis," said Dr. Frazee, chief of acute care surgery at Scott & White Healthcare in Temple, Tex.
His interest in the subject started when his son, an otherwise healthy young adult, complained about having to stay in the hospital after a laparoscopic appendectomy. Dr. Frazee conducted a review of 119 laparoscopic appendectomies at his institution and found that 35% of patients went home the same day, 61% were admitted for a day, and the few others were hospitalized longer. Morbidity was seen in 8%.
He and his colleagues developed an outpatient protocol in July 2010, under which patients undergoing uncomplicated laparoscopic appendectomies would not be admitted unless they were pregnant or younger than 17 years, or if a perforated or gangrenous appendicitis was discovered during the surgery. To qualify for same-day discharge, outpatients had to be able to tolerate intake of liquids, ambulate, urinate, and have adequate respiratory effort. They also had to be hemodynamically stable, have pain controlled with oral analgesics, have nausea and vomiting controlled, show no alteration in mental status from baseline, have the approval of their physician, and have appropriate supervision and assistance at home.
An initial review compared 116 patients treated under the protocol in 2010-2011 with historical controls and found a significant reduction in length of stay without increased morbidity. Under the protocol, 85% of patients were outpatients, compared with 35% in the control group. Postoperative morbidity affected 5% in the protocol group and 8% in the control group, and no patients were readmitted (Am. Surg. 2012;215:101-5).
Since then, the outpatient protocol has been the standard of care at his institution. The current report covers 166 men and 179 women treated under the protocol from July 2010 through December 2012. They had a mean age of 35 years and a mean body mass index of 31 kg/m2. Thirty-two percent had a history of prior abdominal surgery. Comorbidities at baseline included hypertension in 29%, diabetes in 11%, coronary artery disease in 4%, and chronic obstructive pulmonary disease in 1%.
Outpatients were sent home from the day surgery unit or the post–anesthetic care unit. Thirty percent were dismissed between 6 a.m. and noon, 15% went home between noon and 6 p.m., 25% were dismissed between 6 p.m. and midnight, and 30% went home between midnight and 6 a.m.
The investigators now are conducting a follow-up study to assess patient satisfaction with the protocol. "Our impression is that they like going home the same day," but a study will confirm whether this is true or not, he said.
Dr. Frazee reported having no financial disclosures.
AT THE AAST ANNUAL MEETING
Major finding: Outpatient laparoscopic uncomplicated appendectomies increased from 35% to 88% of the procedures under the outpatient protocol.
Data source: Review of 345 outpatient procedures at one institution from July 2010 through December 2012, compared with historical controls.
Disclosures: Dr. Frazee reported having no financial disclosures.
Don’t Rush to Lymph Node Biopsy
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
EXPERT ANALYSIS FROM THE PDA ANNUAL MEETING
Don’t rush to lymph node biopsy for thin melanomas, expert says
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.
Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.
"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.
The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.
Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).
Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.
A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.
There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.
"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.
In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."
One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.
Dr. Swetter reported having no relevant financial disclosures.
On Twitter @sherryboschert
EXPERT ANALYSIS FROM THE PDA ANNUAL MEETING
New GI, topical approaches target rosacea
SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.
"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.
Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.
The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.
That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).
Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.
A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).
"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."
Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.
The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.
"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.
Brimonidine is a highly selective alpha2-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.
Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).
The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.
"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.
Dr. Shinkai reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.
"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.
Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.
The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.
That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).
Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.
A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).
"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."
Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.
The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.
"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.
Brimonidine is a highly selective alpha2-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.
Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).
The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.
"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.
Dr. Shinkai reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.
"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.
Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.
The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.
That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).
Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.
A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).
"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."
Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.
The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.
"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.
Brimonidine is a highly selective alpha2-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.
Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).
The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.
"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.
Dr. Shinkai reported having no relevant financial disclosures.
On Twitter @sherryboschert
EXPERT ANALYSIS FROM THE PDA ANNUAL MEETING
