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Thyroid cancer rise mostly overdiagnosis
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
FROM JAMA OTOLARYNGOLOGY – HEAD & NECK SURGERY
Cladribine effective in early MS, but safety fears persist
The oral immunosuppressant drug cladribine delays conversion to clinically definite multiple sclerosis in patients with a demyelinating event, according to results from a randomized controlled trial.
Cladribine, also used as a chemotherapy agent, was shown in a previous trial to be effective in relapsing MS (N. Engl. J. Med. 2010;362:416-26). However, regulators’ concerns about cladribine’s long-term safety risks – particularly prolonged lymphopenia, infections, and malignancies – caused its manufacturer, Merck, to withdraw its U.S. and European bids for approval as a multiple sclerosis (MS) treatment in 2011. The current trial, called ORACLE MS, led by Dr. Thomas Leist of Thomas Jefferson University, Philadelphia, was stopped the same year with about 60% of patients completing the full 96 weeks, although follow-up continued for 24 weeks after the final dose.
With several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile, cautioned Dr. Cameron and Dr. Bourdette.Dr. Leist and his colleagues randomized 617 patients with MRI evidence of a demyelinating event to cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, or placebo. Cladribine was seen associated with a significant risk reduction for time to conversion to clinically definite MS, compared with placebo: The hazard ratios were 0.38 for the 5.25-mg/kg dose and 0.33 for the 3.5-mg/kg dose. Lymphopenia was reported in 5% of patients in the higher-dose group and 2% of patients in the lower-dose group. The investigators concluded that cladribine had potential benefit as an induction agent for people in the early stages of MS (Lancet Neurol. 2014;13:257-67) .
In an editorial accompanying the study, Dr. Michelle H. Cameron and Dr. Dennis Bourdette of Oregon Health and Science University in Portland, cautioned that with several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile. "When treating MS, a disease that is rarely fatal, has a highly variable course, and lasts decades after diagnosis, the wisdom of accepting serious risks such as opportunistic infections and malignancies is questionable," they wrote. First-generation MS treatments such as beta-interferons and glatiramer acetate, they noted, "are inconvenient since they require self-injections." However, these are efficacious "and have proven to be safe for more than 20 years. We have not been so fortunate with some subsequent therapies," Dr. Cameron and Dr. Bourdette added, citing mitoxantrone and natalizumab as two whose risks became clear after marketing approval (Lancet Neurol. 2014;13:235-7).
Dr. Leist and his colleagues’ study was funded by Merck; Dr. Leist and his coauthors disclosed financial relationships with Merck and/or other manufacturers. Two were employees of a Merck subsidiary, EMD Serono, at the time the study was submitted. Dr. Cameron disclosed prior support from Acorda Therapeutics, and Dr. Bourdette disclosed funding from Teva, Biogen Idec, Elan, and Genzyme.
The oral immunosuppressant drug cladribine delays conversion to clinically definite multiple sclerosis in patients with a demyelinating event, according to results from a randomized controlled trial.
Cladribine, also used as a chemotherapy agent, was shown in a previous trial to be effective in relapsing MS (N. Engl. J. Med. 2010;362:416-26). However, regulators’ concerns about cladribine’s long-term safety risks – particularly prolonged lymphopenia, infections, and malignancies – caused its manufacturer, Merck, to withdraw its U.S. and European bids for approval as a multiple sclerosis (MS) treatment in 2011. The current trial, called ORACLE MS, led by Dr. Thomas Leist of Thomas Jefferson University, Philadelphia, was stopped the same year with about 60% of patients completing the full 96 weeks, although follow-up continued for 24 weeks after the final dose.
With several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile, cautioned Dr. Cameron and Dr. Bourdette.Dr. Leist and his colleagues randomized 617 patients with MRI evidence of a demyelinating event to cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, or placebo. Cladribine was seen associated with a significant risk reduction for time to conversion to clinically definite MS, compared with placebo: The hazard ratios were 0.38 for the 5.25-mg/kg dose and 0.33 for the 3.5-mg/kg dose. Lymphopenia was reported in 5% of patients in the higher-dose group and 2% of patients in the lower-dose group. The investigators concluded that cladribine had potential benefit as an induction agent for people in the early stages of MS (Lancet Neurol. 2014;13:257-67) .
In an editorial accompanying the study, Dr. Michelle H. Cameron and Dr. Dennis Bourdette of Oregon Health and Science University in Portland, cautioned that with several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile. "When treating MS, a disease that is rarely fatal, has a highly variable course, and lasts decades after diagnosis, the wisdom of accepting serious risks such as opportunistic infections and malignancies is questionable," they wrote. First-generation MS treatments such as beta-interferons and glatiramer acetate, they noted, "are inconvenient since they require self-injections." However, these are efficacious "and have proven to be safe for more than 20 years. We have not been so fortunate with some subsequent therapies," Dr. Cameron and Dr. Bourdette added, citing mitoxantrone and natalizumab as two whose risks became clear after marketing approval (Lancet Neurol. 2014;13:235-7).
Dr. Leist and his colleagues’ study was funded by Merck; Dr. Leist and his coauthors disclosed financial relationships with Merck and/or other manufacturers. Two were employees of a Merck subsidiary, EMD Serono, at the time the study was submitted. Dr. Cameron disclosed prior support from Acorda Therapeutics, and Dr. Bourdette disclosed funding from Teva, Biogen Idec, Elan, and Genzyme.
The oral immunosuppressant drug cladribine delays conversion to clinically definite multiple sclerosis in patients with a demyelinating event, according to results from a randomized controlled trial.
Cladribine, also used as a chemotherapy agent, was shown in a previous trial to be effective in relapsing MS (N. Engl. J. Med. 2010;362:416-26). However, regulators’ concerns about cladribine’s long-term safety risks – particularly prolonged lymphopenia, infections, and malignancies – caused its manufacturer, Merck, to withdraw its U.S. and European bids for approval as a multiple sclerosis (MS) treatment in 2011. The current trial, called ORACLE MS, led by Dr. Thomas Leist of Thomas Jefferson University, Philadelphia, was stopped the same year with about 60% of patients completing the full 96 weeks, although follow-up continued for 24 weeks after the final dose.
With several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile, cautioned Dr. Cameron and Dr. Bourdette.Dr. Leist and his colleagues randomized 617 patients with MRI evidence of a demyelinating event to cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, or placebo. Cladribine was seen associated with a significant risk reduction for time to conversion to clinically definite MS, compared with placebo: The hazard ratios were 0.38 for the 5.25-mg/kg dose and 0.33 for the 3.5-mg/kg dose. Lymphopenia was reported in 5% of patients in the higher-dose group and 2% of patients in the lower-dose group. The investigators concluded that cladribine had potential benefit as an induction agent for people in the early stages of MS (Lancet Neurol. 2014;13:257-67) .
In an editorial accompanying the study, Dr. Michelle H. Cameron and Dr. Dennis Bourdette of Oregon Health and Science University in Portland, cautioned that with several better-studied agents to choose from, clinicians should not put the convenience of oral dosing above an uncertain safety profile. "When treating MS, a disease that is rarely fatal, has a highly variable course, and lasts decades after diagnosis, the wisdom of accepting serious risks such as opportunistic infections and malignancies is questionable," they wrote. First-generation MS treatments such as beta-interferons and glatiramer acetate, they noted, "are inconvenient since they require self-injections." However, these are efficacious "and have proven to be safe for more than 20 years. We have not been so fortunate with some subsequent therapies," Dr. Cameron and Dr. Bourdette added, citing mitoxantrone and natalizumab as two whose risks became clear after marketing approval (Lancet Neurol. 2014;13:235-7).
Dr. Leist and his colleagues’ study was funded by Merck; Dr. Leist and his coauthors disclosed financial relationships with Merck and/or other manufacturers. Two were employees of a Merck subsidiary, EMD Serono, at the time the study was submitted. Dr. Cameron disclosed prior support from Acorda Therapeutics, and Dr. Bourdette disclosed funding from Teva, Biogen Idec, Elan, and Genzyme.
FROM LANCET NEUROLOGY
Topical treatments for psoriasis: Molecules to watch
Though it’s been more than a decade since a new class of topical medication has been approved for psoriasis, there are several promising new anti-inflammatory compounds to keep an eye on, says Dr. Linda Stein Gold.
Dr. Stein Gold, director of dermatology clinical research and division head of dermatology in the Henry Ford Health System in Detroit and West Bloomfield, Mich., highlighted several molecules first developed as oral therapies that are now under clinical investigation as topical treatments for psoriasis. If successful in phase III trials, these could offer important alternatives to topical steroids and vitamin D analogues, she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
Steroids can cause skin atrophy, among other adverse effects, when used long term, and vitamin D analogues can cause irritation.
The topical treatments in development, if successful, could fill an important need for patients whose disease is not severe enough to require systemic treatments, or as add-on therapies for patients whose psoriasis is not adequately controlled with systemic treatments.
Dr. Stein Gold named Janus kinase (JAK) inhibitors as a key group of medicines that block cytokine signaling in receptors involved in psoriasis. One topical formulation containing JAK 1 and 2 inhibitor was shown in a 2012 phase II trial (n = 29) to be well tolerated and to improve lesion thickness, scaling, and total area, with few and mild adverse events (J. Am. Acad. Dermatol. 2012;67:658-64).
A different JAK inhibitor, tofacitinib, which has also been studied in oral formulations as a treatment for psoriasis, was also recently shown to be effective as a topical formulation, improving clinical signs of plaque psoriasis in a 2013 phase IIa trial (Br. J. Dermatol. 2013;169:137-45)
Finally, Dr. Stein Gold talked about AN2728, a boron-containing molecule that works by inhibiting phosphodiesterase 4. Topical treatment with AN2728 was seen in a 2011 manufacturer-sponsored phase II study (n = 140) to show significant reductions in thickness and clinical improvement in the psoriatic plaque without dermal irritation. (41st ESDR, Barcelona, poster 244)
Dr. Stein Gold stressed the validity of complementary treatment with both topical corticosteroids and vitamin D analogues in psoriasis – and even topical tazarotene and tar – but said there was an "active future" for the new molecules.
Dr. Stein Gold disclosed relationships with Leo, Medicis, Stiefel, Galderma, Novartis, and Taro. SDEF and this news organization are owned by the same parent company.
Though it’s been more than a decade since a new class of topical medication has been approved for psoriasis, there are several promising new anti-inflammatory compounds to keep an eye on, says Dr. Linda Stein Gold.
Dr. Stein Gold, director of dermatology clinical research and division head of dermatology in the Henry Ford Health System in Detroit and West Bloomfield, Mich., highlighted several molecules first developed as oral therapies that are now under clinical investigation as topical treatments for psoriasis. If successful in phase III trials, these could offer important alternatives to topical steroids and vitamin D analogues, she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
Steroids can cause skin atrophy, among other adverse effects, when used long term, and vitamin D analogues can cause irritation.
The topical treatments in development, if successful, could fill an important need for patients whose disease is not severe enough to require systemic treatments, or as add-on therapies for patients whose psoriasis is not adequately controlled with systemic treatments.
Dr. Stein Gold named Janus kinase (JAK) inhibitors as a key group of medicines that block cytokine signaling in receptors involved in psoriasis. One topical formulation containing JAK 1 and 2 inhibitor was shown in a 2012 phase II trial (n = 29) to be well tolerated and to improve lesion thickness, scaling, and total area, with few and mild adverse events (J. Am. Acad. Dermatol. 2012;67:658-64).
A different JAK inhibitor, tofacitinib, which has also been studied in oral formulations as a treatment for psoriasis, was also recently shown to be effective as a topical formulation, improving clinical signs of plaque psoriasis in a 2013 phase IIa trial (Br. J. Dermatol. 2013;169:137-45)
Finally, Dr. Stein Gold talked about AN2728, a boron-containing molecule that works by inhibiting phosphodiesterase 4. Topical treatment with AN2728 was seen in a 2011 manufacturer-sponsored phase II study (n = 140) to show significant reductions in thickness and clinical improvement in the psoriatic plaque without dermal irritation. (41st ESDR, Barcelona, poster 244)
Dr. Stein Gold stressed the validity of complementary treatment with both topical corticosteroids and vitamin D analogues in psoriasis – and even topical tazarotene and tar – but said there was an "active future" for the new molecules.
Dr. Stein Gold disclosed relationships with Leo, Medicis, Stiefel, Galderma, Novartis, and Taro. SDEF and this news organization are owned by the same parent company.
Though it’s been more than a decade since a new class of topical medication has been approved for psoriasis, there are several promising new anti-inflammatory compounds to keep an eye on, says Dr. Linda Stein Gold.
Dr. Stein Gold, director of dermatology clinical research and division head of dermatology in the Henry Ford Health System in Detroit and West Bloomfield, Mich., highlighted several molecules first developed as oral therapies that are now under clinical investigation as topical treatments for psoriasis. If successful in phase III trials, these could offer important alternatives to topical steroids and vitamin D analogues, she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
Steroids can cause skin atrophy, among other adverse effects, when used long term, and vitamin D analogues can cause irritation.
The topical treatments in development, if successful, could fill an important need for patients whose disease is not severe enough to require systemic treatments, or as add-on therapies for patients whose psoriasis is not adequately controlled with systemic treatments.
Dr. Stein Gold named Janus kinase (JAK) inhibitors as a key group of medicines that block cytokine signaling in receptors involved in psoriasis. One topical formulation containing JAK 1 and 2 inhibitor was shown in a 2012 phase II trial (n = 29) to be well tolerated and to improve lesion thickness, scaling, and total area, with few and mild adverse events (J. Am. Acad. Dermatol. 2012;67:658-64).
A different JAK inhibitor, tofacitinib, which has also been studied in oral formulations as a treatment for psoriasis, was also recently shown to be effective as a topical formulation, improving clinical signs of plaque psoriasis in a 2013 phase IIa trial (Br. J. Dermatol. 2013;169:137-45)
Finally, Dr. Stein Gold talked about AN2728, a boron-containing molecule that works by inhibiting phosphodiesterase 4. Topical treatment with AN2728 was seen in a 2011 manufacturer-sponsored phase II study (n = 140) to show significant reductions in thickness and clinical improvement in the psoriatic plaque without dermal irritation. (41st ESDR, Barcelona, poster 244)
Dr. Stein Gold stressed the validity of complementary treatment with both topical corticosteroids and vitamin D analogues in psoriasis – and even topical tazarotene and tar – but said there was an "active future" for the new molecules.
Dr. Stein Gold disclosed relationships with Leo, Medicis, Stiefel, Galderma, Novartis, and Taro. SDEF and this news organization are owned by the same parent company.
FROM SDEF HAWAII DERMATOLOGY SEMINAR
Ingenol mebutate improves outcomes in actinic keratosis
Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.
Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.
At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).
In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.
The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.
The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.
Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.
Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.
Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.
Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.
Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.
At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).
In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.
The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.
The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.
Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.
Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.
Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.
Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.
Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.
At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).
In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.
The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.
The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.
Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.
Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.
Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.
FROM SDEF HAWAII DERMATOLOGY SEMINAR
Major finding: Ingenol mebutate gel following cryosurgery significantly improved complete clearance rates, compared with vehicle gel at 12 months (30.5% vs. 18.5%; P =.01). Mean percentage reduction of AK lesions at 12 months was significantly higher with ingenol mebutate for all lesions than with vehicle (59.5% vs. 44.4%; P = .004)
Data source: Phase III multicenter, randomized, double-blind study of 329 patients with actinic keratosis on the face or scalp.
Disclosures: Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott.
Sleep apnea may be underdiagnosed in multiple sclerosis
Sleep disturbances, including obstructive sleep apnea, may be contributing to daytime fatigue in a large proportion of people with multiple sclerosis, based on the results of an observational study of 195 MS patients without additional neurologic disorders, such as Parkinson’s disease or stroke, which could independently increase OSA risk.
Obstructive sleep apnea – a common and treatable disorder – is likely underrecognized in this patient group as aggravating or causing fatigue, according to the investigators, led by Dr. Tiffany J. Braley of the multiple sclerosis center at the University of Michigan, Ann Arbor.
More than half of all subjects, they found, had evidence of an elevated risk for OSA, and a fifth had a prior diagnosis of OSA. OSA risk emerged as a significant predictor of fatigue severity after adjusting for confounding factors.
In the study, Dr. Braley and her colleagues administered a validated OSA scoring tool called STOP-Bang to all participants to collect information related to snoring, observed apnea, fatigue, blood pressure, body mass index, age, neck circumference, and gender. They also conducted an extensive sleep questionnaire and administrated validated fatigue, insomnia, and sleepiness scoring tools. The researchers consulted patient medical records to assess information on disease severity, depression, and disability (J. Clin. Sleep Med. 2014;10:155-62).
The patients had a mean age of 47 years, and 66% were female. Overall, 41 (21%) had a prior OSA diagnosis, and 110 (56%) had a STOP-Bang score of 3 or greater, which is indicative of elevated OSA risk. A STOP-Bang score of 3 or more functioned as a significant predictor of higher fatigue scores (P = .01). More nocturnal symptoms and higher disability levels also predicted fatigue.
The proportion of subjects at risk of OSA in the study was at the high end of previous estimates in MS patients, Dr. Braley and her colleagues wrote, but they were surprised to find relatively few OSA diagnoses while more than half the cohort had elevated risk, suggesting that the findings may reflect "suboptimal OSA diagnosis patterns."
"Underrecognition of other symptoms that may signal OSA – such as fatigue – may also explain the discrepancy we found, particularly in patients who suffer disproportionately from fatigue because of a comorbid condition (MS)," they wrote.
The investigators noted that the cross-sectional, observational design of their study meant that they could not establish OSA as causing fatigue in the cohort, and acknowledged that sleep disturbance related to other causes could be contributing. In addition, they cautioned, this was a single-site study, and the findings could reflect characteristics of patients referred to the investigators’ clinic.
Nonetheless, they wrote, clinicians caring for patients with MS "should maintain a low threshold" to screen for OSA, and make efforts to identify any nocturnal symptoms that could affect patients’ sleep quality and contribute to daytime fatigue.
The investigators estimated that as much as 40% of fatigue in MS could be eliminated through better diagnosis and successful treatment of patients with OSA.
The study had no outside funding. Dr. Braley and her two coauthors have received research support from companies marketing multiple sclerosis drugs or OSA therapies and in some instances received compensation for activities with such companies. Dr. Braley and coauthors have been named in patents or provisional patents for sleep apnea treatments held by the University of Michigan.
Sleep disturbances, including obstructive sleep apnea, may be contributing to daytime fatigue in a large proportion of people with multiple sclerosis, based on the results of an observational study of 195 MS patients without additional neurologic disorders, such as Parkinson’s disease or stroke, which could independently increase OSA risk.
Obstructive sleep apnea – a common and treatable disorder – is likely underrecognized in this patient group as aggravating or causing fatigue, according to the investigators, led by Dr. Tiffany J. Braley of the multiple sclerosis center at the University of Michigan, Ann Arbor.
More than half of all subjects, they found, had evidence of an elevated risk for OSA, and a fifth had a prior diagnosis of OSA. OSA risk emerged as a significant predictor of fatigue severity after adjusting for confounding factors.
In the study, Dr. Braley and her colleagues administered a validated OSA scoring tool called STOP-Bang to all participants to collect information related to snoring, observed apnea, fatigue, blood pressure, body mass index, age, neck circumference, and gender. They also conducted an extensive sleep questionnaire and administrated validated fatigue, insomnia, and sleepiness scoring tools. The researchers consulted patient medical records to assess information on disease severity, depression, and disability (J. Clin. Sleep Med. 2014;10:155-62).
The patients had a mean age of 47 years, and 66% were female. Overall, 41 (21%) had a prior OSA diagnosis, and 110 (56%) had a STOP-Bang score of 3 or greater, which is indicative of elevated OSA risk. A STOP-Bang score of 3 or more functioned as a significant predictor of higher fatigue scores (P = .01). More nocturnal symptoms and higher disability levels also predicted fatigue.
The proportion of subjects at risk of OSA in the study was at the high end of previous estimates in MS patients, Dr. Braley and her colleagues wrote, but they were surprised to find relatively few OSA diagnoses while more than half the cohort had elevated risk, suggesting that the findings may reflect "suboptimal OSA diagnosis patterns."
"Underrecognition of other symptoms that may signal OSA – such as fatigue – may also explain the discrepancy we found, particularly in patients who suffer disproportionately from fatigue because of a comorbid condition (MS)," they wrote.
The investigators noted that the cross-sectional, observational design of their study meant that they could not establish OSA as causing fatigue in the cohort, and acknowledged that sleep disturbance related to other causes could be contributing. In addition, they cautioned, this was a single-site study, and the findings could reflect characteristics of patients referred to the investigators’ clinic.
Nonetheless, they wrote, clinicians caring for patients with MS "should maintain a low threshold" to screen for OSA, and make efforts to identify any nocturnal symptoms that could affect patients’ sleep quality and contribute to daytime fatigue.
The investigators estimated that as much as 40% of fatigue in MS could be eliminated through better diagnosis and successful treatment of patients with OSA.
The study had no outside funding. Dr. Braley and her two coauthors have received research support from companies marketing multiple sclerosis drugs or OSA therapies and in some instances received compensation for activities with such companies. Dr. Braley and coauthors have been named in patents or provisional patents for sleep apnea treatments held by the University of Michigan.
Sleep disturbances, including obstructive sleep apnea, may be contributing to daytime fatigue in a large proportion of people with multiple sclerosis, based on the results of an observational study of 195 MS patients without additional neurologic disorders, such as Parkinson’s disease or stroke, which could independently increase OSA risk.
Obstructive sleep apnea – a common and treatable disorder – is likely underrecognized in this patient group as aggravating or causing fatigue, according to the investigators, led by Dr. Tiffany J. Braley of the multiple sclerosis center at the University of Michigan, Ann Arbor.
More than half of all subjects, they found, had evidence of an elevated risk for OSA, and a fifth had a prior diagnosis of OSA. OSA risk emerged as a significant predictor of fatigue severity after adjusting for confounding factors.
In the study, Dr. Braley and her colleagues administered a validated OSA scoring tool called STOP-Bang to all participants to collect information related to snoring, observed apnea, fatigue, blood pressure, body mass index, age, neck circumference, and gender. They also conducted an extensive sleep questionnaire and administrated validated fatigue, insomnia, and sleepiness scoring tools. The researchers consulted patient medical records to assess information on disease severity, depression, and disability (J. Clin. Sleep Med. 2014;10:155-62).
The patients had a mean age of 47 years, and 66% were female. Overall, 41 (21%) had a prior OSA diagnosis, and 110 (56%) had a STOP-Bang score of 3 or greater, which is indicative of elevated OSA risk. A STOP-Bang score of 3 or more functioned as a significant predictor of higher fatigue scores (P = .01). More nocturnal symptoms and higher disability levels also predicted fatigue.
The proportion of subjects at risk of OSA in the study was at the high end of previous estimates in MS patients, Dr. Braley and her colleagues wrote, but they were surprised to find relatively few OSA diagnoses while more than half the cohort had elevated risk, suggesting that the findings may reflect "suboptimal OSA diagnosis patterns."
"Underrecognition of other symptoms that may signal OSA – such as fatigue – may also explain the discrepancy we found, particularly in patients who suffer disproportionately from fatigue because of a comorbid condition (MS)," they wrote.
The investigators noted that the cross-sectional, observational design of their study meant that they could not establish OSA as causing fatigue in the cohort, and acknowledged that sleep disturbance related to other causes could be contributing. In addition, they cautioned, this was a single-site study, and the findings could reflect characteristics of patients referred to the investigators’ clinic.
Nonetheless, they wrote, clinicians caring for patients with MS "should maintain a low threshold" to screen for OSA, and make efforts to identify any nocturnal symptoms that could affect patients’ sleep quality and contribute to daytime fatigue.
The investigators estimated that as much as 40% of fatigue in MS could be eliminated through better diagnosis and successful treatment of patients with OSA.
The study had no outside funding. Dr. Braley and her two coauthors have received research support from companies marketing multiple sclerosis drugs or OSA therapies and in some instances received compensation for activities with such companies. Dr. Braley and coauthors have been named in patents or provisional patents for sleep apnea treatments held by the University of Michigan.
FROM THE JOURNAL OF CLINICAL SLEEP MEDICINE
Major finding: Overall, 41 (21%) had a prior OSA diagnosis, and 110 (56%) had a STOP-Bang score of 3 or greater, which is indicative of elevated OSA risk.
Data source: A cross-sectional observational study using validated questionnaires measuring sleep quality, fatigue, and apnea risk along with patient medical records from cohort of 195 MS patients treated at a university MS clinic over 9 months.
Disclosures: The study had no outside funding. Dr. Braley and her two coauthors have received research support from companies marketing multiple sclerosis drugs or OSA therapies and in some instances received compensation for activities with such companies. Dr. Braley and her coauthors have been named in patents or provisional patents for sleep apnea treatments held by the University of Michigan.
Acute kidney injury elevates death risk long after RRT
Acute kidney injury survivors treated with renal replacement therapy in the ICU have high long-term mortality risk, regardless of the type of RRT they received, according to a recent study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published in PLoS Medicine (2014 Feb. 11 [doi:10.1371/journal.pmed.1001601]), come from POST-RENAL, an extended follow-up in a trial of 1,464 adult AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study. Patients were treated in 35 centers in Australia or New Zealand between December 2005 and August 2008.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% confidence interval, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw significantly high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
"Only one-third of randomized patients were alive 3.5 years later, a lower survival than that seen in recognized high mortality conditions such as the acute respiratory distress syndrome. Although, in our patients the risk of subsequent maintenance dialysis dependence is low, almost half have evidence of significant proteinuria, portending further risk in the years to come," Dr. Gallagher and his colleagues said in their analysis.
The findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention," they wrote.
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
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This data showing a relatively low rate of chronic renal replacement therapy will be helpful in counseling critically ill patients with acute kidney injury. The high rate of mortality highlights the importance of further studies into appropriate risk-reduction strategies and interventions for these individuals.
Dr. Seema Chandra is a hospitalist at West Kendall Baptist Hospital and is on the advisory board of Hospitalist News.
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This data showing a relatively low rate of chronic renal replacement therapy will be helpful in counseling critically ill patients with acute kidney injury. The high rate of mortality highlights the importance of further studies into appropriate risk-reduction strategies and interventions for these individuals.
Dr. Seema Chandra is a hospitalist at West Kendall Baptist Hospital and is on the advisory board of Hospitalist News.
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This data showing a relatively low rate of chronic renal replacement therapy will be helpful in counseling critically ill patients with acute kidney injury. The high rate of mortality highlights the importance of further studies into appropriate risk-reduction strategies and interventions for these individuals.
Dr. Seema Chandra is a hospitalist at West Kendall Baptist Hospital and is on the advisory board of Hospitalist News.
Acute kidney injury survivors treated with renal replacement therapy in the ICU have high long-term mortality risk, regardless of the type of RRT they received, according to a recent study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published in PLoS Medicine (2014 Feb. 11 [doi:10.1371/journal.pmed.1001601]), come from POST-RENAL, an extended follow-up in a trial of 1,464 adult AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study. Patients were treated in 35 centers in Australia or New Zealand between December 2005 and August 2008.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% confidence interval, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw significantly high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
"Only one-third of randomized patients were alive 3.5 years later, a lower survival than that seen in recognized high mortality conditions such as the acute respiratory distress syndrome. Although, in our patients the risk of subsequent maintenance dialysis dependence is low, almost half have evidence of significant proteinuria, portending further risk in the years to come," Dr. Gallagher and his colleagues said in their analysis.
The findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention," they wrote.
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
Acute kidney injury survivors treated with renal replacement therapy in the ICU have high long-term mortality risk, regardless of the type of RRT they received, according to a recent study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published in PLoS Medicine (2014 Feb. 11 [doi:10.1371/journal.pmed.1001601]), come from POST-RENAL, an extended follow-up in a trial of 1,464 adult AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study. Patients were treated in 35 centers in Australia or New Zealand between December 2005 and August 2008.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% confidence interval, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw significantly high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
"Only one-third of randomized patients were alive 3.5 years later, a lower survival than that seen in recognized high mortality conditions such as the acute respiratory distress syndrome. Although, in our patients the risk of subsequent maintenance dialysis dependence is low, almost half have evidence of significant proteinuria, portending further risk in the years to come," Dr. Gallagher and his colleagues said in their analysis.
The findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention," they wrote.
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
FROM PLOS MEDICINE
Acute kidney injury elevates death risk long after RRT
People with acute kidney injury receiving renal replacement therapy have an increased long-term risk of dying regardless of the type of RRT they receive, according to a new study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published Feb. 11 in PLoS Medicine (2014 Feb. 11 [doi: 10.1371/journal.pmed.1001601]), come from extended follow-up in a trial of 1,464 AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% CI, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
Dr. Gallagher and his colleagues wrote in their analysis that the findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention."
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
People with acute kidney injury receiving renal replacement therapy have an increased long-term risk of dying regardless of the type of RRT they receive, according to a new study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published Feb. 11 in PLoS Medicine (2014 Feb. 11 [doi: 10.1371/journal.pmed.1001601]), come from extended follow-up in a trial of 1,464 AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% CI, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
Dr. Gallagher and his colleagues wrote in their analysis that the findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention."
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
People with acute kidney injury receiving renal replacement therapy have an increased long-term risk of dying regardless of the type of RRT they receive, according to a new study.
Intensity of RRT performed in intensive care units, researchers also found, made no difference in the likelihood of a patient needing maintenance dialysis or having protein in the urine within 4 years after the intervention.
The results, published Feb. 11 in PLoS Medicine (2014 Feb. 11 [doi: 10.1371/journal.pmed.1001601]), come from extended follow-up in a trial of 1,464 AKI patients in ICUs who were randomized to receive RRT of higher or lower intensity. Dr. Martin Gallagher of the George Institute for Global Health in Sydney, Australia, led the study.
The researchers did not see high-intensity RRT associated with any improvements in long-term survival: At a median of 43.9 months after randomization, 63% of patients in the lower-intensity group and 62% of patients in the higher-intensity group had died (risk ratio, 1.04; 95% CI, 0.96-1.12; P = .49).
Of the 810 patients who survived more than 90 days past randomization, rates of maintenance dialysis were similarly low: 5.1% for the lower-intensity RRT group and 5.8% for the higher-intensity group (RR, 1.12; 95% CI, 0.63-2.00; P = .69). Both groups, however, saw high rates of albuminuria: 40% and 44%, respectively (P = .48). Chronic proteinuria is an established risk factor for death, cardiovascular disease, and additional dialysis.
Dr. Gallagher and his colleagues wrote in their analysis that the findings "support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention."
The study was supported by the Australian government. One coauthor, Dr. Rinaldo Bellomo, disclosed receiving financial support from Eli Lilly, Cardinal Health, and CSL Bioplasma. The George Institute for Global Health, Dr. Gallagher’s institution, has received research funding from Servier, Novartis, and other companies.
FROM PLOS MEDICINE
Two doses of HPV vaccine effective against condyloma
Two doses of a human papillomavirus vaccine significantly reduced the risk of developing genital warts in a large cohort of girls and women in Sweden; subjects who had received the full scheduled three doses saw an even lower risk.
The research, published online Feb. 11 in JAMA, did not look at risk reduction for cervical cancer – the main goal of human papillomavirus (HPV) vaccination programs – but instead looked at the earliest HPV-related disease outcome that can be measured (JAMA 2014 Feb. 11 [doi:10.1001/jama.2014.95]).
In the study, Eva Herweijer of Karolinska Institutet, Stockholm, and her colleagues examined Swedish population-based health registries for data on HPV vaccination and first appearance of condyloma, (warts), in a cohort of 1,045,165 girls and women between the ages of 10 and 24 years who were followed up between 2006 and 2010. The treatment used in Sweden’s program was a quadrivalent vaccine that covered HPV 16 and 18, the types linked with cervical cancer, and also HPV 6 and 11, which are associated with condyloma.
Girls aged 10-16 at the time of vaccination who received the full three doses saw the lowest incidence rate ratio of 0.18 (95% CI, 0.15-0.22), while girls in the same age group receiving two doses saw an IRR of 0.29 (95% CI, 0.21-0.40). The number of cases prevented by three doses compared with two doses was 59 cases per 100,000 person-years, "which is a small difference," Ms. Herweijer and her colleagues wrote in their analysis. They noted that the three-dose schedule is associated with cost and feasibility concerns. Of the subjects in the cohort who were vaccinated, less than a third received the full three doses.
"Previous national studies," the investigators wrote, "have examined the effect of HPV vaccination; however, none to date have examined associations by vaccine dose level, which is important because actual vaccination programs include substantial numbers of women who do not complete the full vaccination schedule." They stressed that studies with longer follow-up would be needed to assess whether a dose-related reduction could be seen for other disease outcomes, importantly neoplasia and cancer.
Ms. Herweijer and her colleagues’ study was funded by the Swedish Foundation for Strategic Research. Four of her coauthors, Dr. Joakim Dillner, Eva Netterlid, Ph.D., Pa¨r Sparén, and Lisen Arnheim-Dahlstro¨m, Ph.D., reported having received previous financial support from Merck, Sanofi Pasteur, and GlaxoSmithKline.
Two doses of a human papillomavirus vaccine significantly reduced the risk of developing genital warts in a large cohort of girls and women in Sweden; subjects who had received the full scheduled three doses saw an even lower risk.
The research, published online Feb. 11 in JAMA, did not look at risk reduction for cervical cancer – the main goal of human papillomavirus (HPV) vaccination programs – but instead looked at the earliest HPV-related disease outcome that can be measured (JAMA 2014 Feb. 11 [doi:10.1001/jama.2014.95]).
In the study, Eva Herweijer of Karolinska Institutet, Stockholm, and her colleagues examined Swedish population-based health registries for data on HPV vaccination and first appearance of condyloma, (warts), in a cohort of 1,045,165 girls and women between the ages of 10 and 24 years who were followed up between 2006 and 2010. The treatment used in Sweden’s program was a quadrivalent vaccine that covered HPV 16 and 18, the types linked with cervical cancer, and also HPV 6 and 11, which are associated with condyloma.
Girls aged 10-16 at the time of vaccination who received the full three doses saw the lowest incidence rate ratio of 0.18 (95% CI, 0.15-0.22), while girls in the same age group receiving two doses saw an IRR of 0.29 (95% CI, 0.21-0.40). The number of cases prevented by three doses compared with two doses was 59 cases per 100,000 person-years, "which is a small difference," Ms. Herweijer and her colleagues wrote in their analysis. They noted that the three-dose schedule is associated with cost and feasibility concerns. Of the subjects in the cohort who were vaccinated, less than a third received the full three doses.
"Previous national studies," the investigators wrote, "have examined the effect of HPV vaccination; however, none to date have examined associations by vaccine dose level, which is important because actual vaccination programs include substantial numbers of women who do not complete the full vaccination schedule." They stressed that studies with longer follow-up would be needed to assess whether a dose-related reduction could be seen for other disease outcomes, importantly neoplasia and cancer.
Ms. Herweijer and her colleagues’ study was funded by the Swedish Foundation for Strategic Research. Four of her coauthors, Dr. Joakim Dillner, Eva Netterlid, Ph.D., Pa¨r Sparén, and Lisen Arnheim-Dahlstro¨m, Ph.D., reported having received previous financial support from Merck, Sanofi Pasteur, and GlaxoSmithKline.
Two doses of a human papillomavirus vaccine significantly reduced the risk of developing genital warts in a large cohort of girls and women in Sweden; subjects who had received the full scheduled three doses saw an even lower risk.
The research, published online Feb. 11 in JAMA, did not look at risk reduction for cervical cancer – the main goal of human papillomavirus (HPV) vaccination programs – but instead looked at the earliest HPV-related disease outcome that can be measured (JAMA 2014 Feb. 11 [doi:10.1001/jama.2014.95]).
In the study, Eva Herweijer of Karolinska Institutet, Stockholm, and her colleagues examined Swedish population-based health registries for data on HPV vaccination and first appearance of condyloma, (warts), in a cohort of 1,045,165 girls and women between the ages of 10 and 24 years who were followed up between 2006 and 2010. The treatment used in Sweden’s program was a quadrivalent vaccine that covered HPV 16 and 18, the types linked with cervical cancer, and also HPV 6 and 11, which are associated with condyloma.
Girls aged 10-16 at the time of vaccination who received the full three doses saw the lowest incidence rate ratio of 0.18 (95% CI, 0.15-0.22), while girls in the same age group receiving two doses saw an IRR of 0.29 (95% CI, 0.21-0.40). The number of cases prevented by three doses compared with two doses was 59 cases per 100,000 person-years, "which is a small difference," Ms. Herweijer and her colleagues wrote in their analysis. They noted that the three-dose schedule is associated with cost and feasibility concerns. Of the subjects in the cohort who were vaccinated, less than a third received the full three doses.
"Previous national studies," the investigators wrote, "have examined the effect of HPV vaccination; however, none to date have examined associations by vaccine dose level, which is important because actual vaccination programs include substantial numbers of women who do not complete the full vaccination schedule." They stressed that studies with longer follow-up would be needed to assess whether a dose-related reduction could be seen for other disease outcomes, importantly neoplasia and cancer.
Ms. Herweijer and her colleagues’ study was funded by the Swedish Foundation for Strategic Research. Four of her coauthors, Dr. Joakim Dillner, Eva Netterlid, Ph.D., Pa¨r Sparén, and Lisen Arnheim-Dahlstro¨m, Ph.D., reported having received previous financial support from Merck, Sanofi Pasteur, and GlaxoSmithKline.
FROM JAMA
EMS protocols may be delaying treatment for febrile status epilepticus
A study of infants and children with febrile status epilepticus found that convulsing children received antiepileptic drugs a full half-hour into their seizures, a lag to treatment that researchers described as "unacceptable."
Dr. Syndi A. Seinfeld of the department of neurology at Virginia Commonwealth University in Richmond and her colleagues identified a lack of standardized protocol among emergency medical services – not a failure to recognize seizure activity – as the main obstacle to prompt treatment in a review of data from the FEBSTAT (Consequences of Prolonged Febrile Seizures in Childhood) study. Delays to treatment with antiepileptic drugs (AEDs) in the 8-year, multicenter, prospective cohort study correlated with longer seizure duration. The study involved 199 children aged 1 month to 6 years with febrile status epilepticus (FSE) seen at five urban medical centers in the United States during 2003-2010 (Epilepsia 2014 Feb. 6 [doi:10.1111/epi.12526]).
FSE seldom resolves spontaneously, and for the majority of these children, multiple AEDs were needed to stop the seizures.
Emergency medical services (EMS) personnel, involved in more than three-quarters of the cases, recognized all but 12% as involving seizure activity. However, because not all EMS teams are authorized to administer antiepileptic drugs such as diazepam and lorazepam, more than half of subjects were not treated with these until arriving in the emergency department. Median time from seizure onset to first AED was 30 minutes for all subjects.
Of the 179 children who received AEDs, the first drug was given by the family in 1% of cases and by EMS in 41%. The remaining 58% of children were treated only when they reached the emergency department.
The mean seizure duration was 81 minutes among children given medication before arriving in the ED and 95 minutes for those who received their first drug after arrival, which was not a statistically significant difference (P = 0.1). The median time from the first dose of AED to the end of seizure was 38 minutes for all subjects.
Dr. Seinfeld and her colleagues also found that about 20% of the children who were treated with AEDs in any setting received a suboptimal first dose, which may have been because of "fear of respiratory concerns," Dr. Seinfeld said in response to e-mailed questions. Of those treated with AEDs, 78% required treatment with more than one AED; about half received respiratory support from EMS or in the hospital. The study showed that respiratory support was more likely to be needed in kids who had been seizing longer, which is notable because fear of causing respiratory problems "plays a big role" in why treatment is delayed, she said.
"The medicine may require the child to need respiratory support. ... and there have been studies that show that people who get multiple doses of AEDs vs. adequate initial doses are more likely to require respiratory support."
The researchers noted that prolonged seizures of any type are associated with an increased risk of complications. Longer seizure duration has been shown to increase potential risk of short-term morbidity, including intubation related injuries, and long-term morbidity, including consequences of hippocampal injury.
In FSE, the researchers argued in their analysis, "prompt and aggressive treatment" with adequate doses of medication is key. "When initial treatment is significantly delayed, the entire treatment paradigm shifts, which prolongs total seizure duration."
"I think people are aware they need to treat seizures sooner. Recognition of seizures as we reported is not the main problem, though it plays a role. And there are some squads that do try and treat seizures more aggressively. There are squads trying to change their protocols. It’s difficult because there are so many types of EMS – volunteer squads; paid [personnel]; and in remote areas, the fire department and police may be first responders. It’s difficult to coordinate care when you have that many people involved," Dr. Seinfeld said.
She and her colleagues noted as a limitation of their study the fact that recruitment took place after the FSE episode was over. They also noted that the FEBSTAT study used data collected only through 2010. However, EMS protocols have not been standardized in the interim.
"EMS still cannot administer AEDs in many jurisdictions," they wrote. And despite mounting evidence that management of FSE should begin prior to hospital arrival, "most published guidelines are limited to hospital settings."
The FEBSTAT study was funded by the National Institutes of Health. Dr. Seinfeld and her coauthors declared that they had no conflicts of interest.
A study of infants and children with febrile status epilepticus found that convulsing children received antiepileptic drugs a full half-hour into their seizures, a lag to treatment that researchers described as "unacceptable."
Dr. Syndi A. Seinfeld of the department of neurology at Virginia Commonwealth University in Richmond and her colleagues identified a lack of standardized protocol among emergency medical services – not a failure to recognize seizure activity – as the main obstacle to prompt treatment in a review of data from the FEBSTAT (Consequences of Prolonged Febrile Seizures in Childhood) study. Delays to treatment with antiepileptic drugs (AEDs) in the 8-year, multicenter, prospective cohort study correlated with longer seizure duration. The study involved 199 children aged 1 month to 6 years with febrile status epilepticus (FSE) seen at five urban medical centers in the United States during 2003-2010 (Epilepsia 2014 Feb. 6 [doi:10.1111/epi.12526]).
FSE seldom resolves spontaneously, and for the majority of these children, multiple AEDs were needed to stop the seizures.
Emergency medical services (EMS) personnel, involved in more than three-quarters of the cases, recognized all but 12% as involving seizure activity. However, because not all EMS teams are authorized to administer antiepileptic drugs such as diazepam and lorazepam, more than half of subjects were not treated with these until arriving in the emergency department. Median time from seizure onset to first AED was 30 minutes for all subjects.
Of the 179 children who received AEDs, the first drug was given by the family in 1% of cases and by EMS in 41%. The remaining 58% of children were treated only when they reached the emergency department.
The mean seizure duration was 81 minutes among children given medication before arriving in the ED and 95 minutes for those who received their first drug after arrival, which was not a statistically significant difference (P = 0.1). The median time from the first dose of AED to the end of seizure was 38 minutes for all subjects.
Dr. Seinfeld and her colleagues also found that about 20% of the children who were treated with AEDs in any setting received a suboptimal first dose, which may have been because of "fear of respiratory concerns," Dr. Seinfeld said in response to e-mailed questions. Of those treated with AEDs, 78% required treatment with more than one AED; about half received respiratory support from EMS or in the hospital. The study showed that respiratory support was more likely to be needed in kids who had been seizing longer, which is notable because fear of causing respiratory problems "plays a big role" in why treatment is delayed, she said.
"The medicine may require the child to need respiratory support. ... and there have been studies that show that people who get multiple doses of AEDs vs. adequate initial doses are more likely to require respiratory support."
The researchers noted that prolonged seizures of any type are associated with an increased risk of complications. Longer seizure duration has been shown to increase potential risk of short-term morbidity, including intubation related injuries, and long-term morbidity, including consequences of hippocampal injury.
In FSE, the researchers argued in their analysis, "prompt and aggressive treatment" with adequate doses of medication is key. "When initial treatment is significantly delayed, the entire treatment paradigm shifts, which prolongs total seizure duration."
"I think people are aware they need to treat seizures sooner. Recognition of seizures as we reported is not the main problem, though it plays a role. And there are some squads that do try and treat seizures more aggressively. There are squads trying to change their protocols. It’s difficult because there are so many types of EMS – volunteer squads; paid [personnel]; and in remote areas, the fire department and police may be first responders. It’s difficult to coordinate care when you have that many people involved," Dr. Seinfeld said.
She and her colleagues noted as a limitation of their study the fact that recruitment took place after the FSE episode was over. They also noted that the FEBSTAT study used data collected only through 2010. However, EMS protocols have not been standardized in the interim.
"EMS still cannot administer AEDs in many jurisdictions," they wrote. And despite mounting evidence that management of FSE should begin prior to hospital arrival, "most published guidelines are limited to hospital settings."
The FEBSTAT study was funded by the National Institutes of Health. Dr. Seinfeld and her coauthors declared that they had no conflicts of interest.
A study of infants and children with febrile status epilepticus found that convulsing children received antiepileptic drugs a full half-hour into their seizures, a lag to treatment that researchers described as "unacceptable."
Dr. Syndi A. Seinfeld of the department of neurology at Virginia Commonwealth University in Richmond and her colleagues identified a lack of standardized protocol among emergency medical services – not a failure to recognize seizure activity – as the main obstacle to prompt treatment in a review of data from the FEBSTAT (Consequences of Prolonged Febrile Seizures in Childhood) study. Delays to treatment with antiepileptic drugs (AEDs) in the 8-year, multicenter, prospective cohort study correlated with longer seizure duration. The study involved 199 children aged 1 month to 6 years with febrile status epilepticus (FSE) seen at five urban medical centers in the United States during 2003-2010 (Epilepsia 2014 Feb. 6 [doi:10.1111/epi.12526]).
FSE seldom resolves spontaneously, and for the majority of these children, multiple AEDs were needed to stop the seizures.
Emergency medical services (EMS) personnel, involved in more than three-quarters of the cases, recognized all but 12% as involving seizure activity. However, because not all EMS teams are authorized to administer antiepileptic drugs such as diazepam and lorazepam, more than half of subjects were not treated with these until arriving in the emergency department. Median time from seizure onset to first AED was 30 minutes for all subjects.
Of the 179 children who received AEDs, the first drug was given by the family in 1% of cases and by EMS in 41%. The remaining 58% of children were treated only when they reached the emergency department.
The mean seizure duration was 81 minutes among children given medication before arriving in the ED and 95 minutes for those who received their first drug after arrival, which was not a statistically significant difference (P = 0.1). The median time from the first dose of AED to the end of seizure was 38 minutes for all subjects.
Dr. Seinfeld and her colleagues also found that about 20% of the children who were treated with AEDs in any setting received a suboptimal first dose, which may have been because of "fear of respiratory concerns," Dr. Seinfeld said in response to e-mailed questions. Of those treated with AEDs, 78% required treatment with more than one AED; about half received respiratory support from EMS or in the hospital. The study showed that respiratory support was more likely to be needed in kids who had been seizing longer, which is notable because fear of causing respiratory problems "plays a big role" in why treatment is delayed, she said.
"The medicine may require the child to need respiratory support. ... and there have been studies that show that people who get multiple doses of AEDs vs. adequate initial doses are more likely to require respiratory support."
The researchers noted that prolonged seizures of any type are associated with an increased risk of complications. Longer seizure duration has been shown to increase potential risk of short-term morbidity, including intubation related injuries, and long-term morbidity, including consequences of hippocampal injury.
In FSE, the researchers argued in their analysis, "prompt and aggressive treatment" with adequate doses of medication is key. "When initial treatment is significantly delayed, the entire treatment paradigm shifts, which prolongs total seizure duration."
"I think people are aware they need to treat seizures sooner. Recognition of seizures as we reported is not the main problem, though it plays a role. And there are some squads that do try and treat seizures more aggressively. There are squads trying to change their protocols. It’s difficult because there are so many types of EMS – volunteer squads; paid [personnel]; and in remote areas, the fire department and police may be first responders. It’s difficult to coordinate care when you have that many people involved," Dr. Seinfeld said.
She and her colleagues noted as a limitation of their study the fact that recruitment took place after the FSE episode was over. They also noted that the FEBSTAT study used data collected only through 2010. However, EMS protocols have not been standardized in the interim.
"EMS still cannot administer AEDs in many jurisdictions," they wrote. And despite mounting evidence that management of FSE should begin prior to hospital arrival, "most published guidelines are limited to hospital settings."
The FEBSTAT study was funded by the National Institutes of Health. Dr. Seinfeld and her coauthors declared that they had no conflicts of interest.
FROM EPILEPSIA
Major finding: More than half of subjects were not treated with antiepileptic drugs until arriving in the emergency department. Median time from seizure onset to first AED was 30 minutes for all subjects.
Data source: An analysis of data collected from 199 children with febrile status epilepticus in the 8-year, multicenter, prospective FEBSTAT cohort.
Disclosures: The FEBSTAT study was funded by the National Institutes of Health. Dr. Seinfeld and her coauthors declared that they had no conflicts of interest.
TBI survivors see threefold risk of early death
People who survive a traumatic brain injury are three times more likely to die prematurely than are those who have not, according to results from a large population-based study.
The study, which drew from more than 4 decades of data from Swedish national patient registries and death records, also found that nearly half of the TBI patients who died prematurely died from suicide, violence, or injuries.
For their research, published online Jan. 15 (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2013.3935]), investigators, led by Dr. Seena Fazel of Oxford (England) University, evaluated data from 218,300 men and women who had survived for 6 months or more after TBI with age and sex-matched controls (n = 2,163,190).
Of all the TBI patients, 69.3% were men, 80.5% were not married, and 9.3% had preexisting psychiatric disorders, including 4.4% with substance abuse diagnoses.
Dr. Fazel and his colleagues found that the TBI patients saw a threefold higher mortality before age 56 years, compared with controls, even after researchers adjusted for socioeconomic confounders (adjusted odds ratio, 3.2; 95% confidence interval, 3.0-3.4). Of those who died early, the median age was 18.6 years at the time of the TBI and 40.6 years at death.
The study also looked at unaffected siblings of the TBI patients (n = 150,513) and found significantly greater odds of premature death in the TBI group, compared with their siblings (OR, 2.6; 95% CI, 2.3-2.8). Still, the difference was less than that seen with the general population controls, suggesting that some genetic and environmental factors might be partly responsible for the higher mortality.
The rate of premature deaths among the TBI survivors was low overall, but it was higher among those with psychiatric or substance abuse diagnoses. Mortality from suicide, injuries, and assault was significantly higher in the TBI group than the control group, accounting for 48.6% of premature deaths among TBI patients.
Dr. Fazel and his colleagues wrote in their analysis that in light of these findings, clinical guidelines might need to be revised to focus on preventing mortality beyond the first few months after injury and address high rates of psychiatric comorbidity and substance abuse among TBI patients.
In an editorial accompanying Dr. Fazel and his colleagues’ article, Dr. Robert G. Robinson of the department of psychiatry administration at the University of Iowa in Iowa City, proposed that some of the excess mortality seen among the TBI patients might be attributable to personality – something the study authors also acknowledged as a potential confounder (JAMA Psychiatry 2014 Jan. 15 [doi:10.1001/jamapsychiatry.2013.4241]).
"The preponderance of premature deaths due to external factors suggests that one of the most likely explanations for the findings in the current study is the existence of personality characteristics of impulsiveness, risk-taking behaviors, and proneness to substance abuse. These patients incur a TBI and continue to demonstrate these behaviors after the TBI, which ultimately leads to a fatality," Dr. Robinson wrote.
Dr. Robinson, echoing the recommendations of Dr. Fazel and his colleagues, argued that recognizing such patients is important "because half of these deaths are due to preventable behaviors." Some prevention strategies, he wrote, might include screening TBI patients at discharge for personality characteristics and treating those with the most impulsive risk-taking traits, or administering antidepressants to those seen as vulnerable to depression.
The study authors and Dr. Robinson noted among the study’s strengths of its very large sample size, making it the largest of its kind to date, its long follow-up, and its use of sibling controls. One weakness noted by Dr. Robinson was that the cause of the TBI could not be specified in most cases and that the severity of TBI could only be quantified in some cases by duration of hospitalization.
Because pathologic features, symptoms, and the course of TBI can differ depending on the cause or severity of the injury, Dr. Robinson wrote, "further studies in this area should focus on whether the cause of brain injury, type of brain injury, severity of injury, or premorbid personality characteristics are associated with the highest risk of premature deaths."
Dr. Fazel and his colleagues’ study was funded by grants from the Wellcome Trust, the Swedish Prison and Probation Service, and the Swedish Research Council. None of its authors declared conflicts of interest. Dr. Robinson disclosed no conflicts of interest related to his editorial.
People who survive a traumatic brain injury are three times more likely to die prematurely than are those who have not, according to results from a large population-based study.
The study, which drew from more than 4 decades of data from Swedish national patient registries and death records, also found that nearly half of the TBI patients who died prematurely died from suicide, violence, or injuries.
For their research, published online Jan. 15 (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2013.3935]), investigators, led by Dr. Seena Fazel of Oxford (England) University, evaluated data from 218,300 men and women who had survived for 6 months or more after TBI with age and sex-matched controls (n = 2,163,190).
Of all the TBI patients, 69.3% were men, 80.5% were not married, and 9.3% had preexisting psychiatric disorders, including 4.4% with substance abuse diagnoses.
Dr. Fazel and his colleagues found that the TBI patients saw a threefold higher mortality before age 56 years, compared with controls, even after researchers adjusted for socioeconomic confounders (adjusted odds ratio, 3.2; 95% confidence interval, 3.0-3.4). Of those who died early, the median age was 18.6 years at the time of the TBI and 40.6 years at death.
The study also looked at unaffected siblings of the TBI patients (n = 150,513) and found significantly greater odds of premature death in the TBI group, compared with their siblings (OR, 2.6; 95% CI, 2.3-2.8). Still, the difference was less than that seen with the general population controls, suggesting that some genetic and environmental factors might be partly responsible for the higher mortality.
The rate of premature deaths among the TBI survivors was low overall, but it was higher among those with psychiatric or substance abuse diagnoses. Mortality from suicide, injuries, and assault was significantly higher in the TBI group than the control group, accounting for 48.6% of premature deaths among TBI patients.
Dr. Fazel and his colleagues wrote in their analysis that in light of these findings, clinical guidelines might need to be revised to focus on preventing mortality beyond the first few months after injury and address high rates of psychiatric comorbidity and substance abuse among TBI patients.
In an editorial accompanying Dr. Fazel and his colleagues’ article, Dr. Robert G. Robinson of the department of psychiatry administration at the University of Iowa in Iowa City, proposed that some of the excess mortality seen among the TBI patients might be attributable to personality – something the study authors also acknowledged as a potential confounder (JAMA Psychiatry 2014 Jan. 15 [doi:10.1001/jamapsychiatry.2013.4241]).
"The preponderance of premature deaths due to external factors suggests that one of the most likely explanations for the findings in the current study is the existence of personality characteristics of impulsiveness, risk-taking behaviors, and proneness to substance abuse. These patients incur a TBI and continue to demonstrate these behaviors after the TBI, which ultimately leads to a fatality," Dr. Robinson wrote.
Dr. Robinson, echoing the recommendations of Dr. Fazel and his colleagues, argued that recognizing such patients is important "because half of these deaths are due to preventable behaviors." Some prevention strategies, he wrote, might include screening TBI patients at discharge for personality characteristics and treating those with the most impulsive risk-taking traits, or administering antidepressants to those seen as vulnerable to depression.
The study authors and Dr. Robinson noted among the study’s strengths of its very large sample size, making it the largest of its kind to date, its long follow-up, and its use of sibling controls. One weakness noted by Dr. Robinson was that the cause of the TBI could not be specified in most cases and that the severity of TBI could only be quantified in some cases by duration of hospitalization.
Because pathologic features, symptoms, and the course of TBI can differ depending on the cause or severity of the injury, Dr. Robinson wrote, "further studies in this area should focus on whether the cause of brain injury, type of brain injury, severity of injury, or premorbid personality characteristics are associated with the highest risk of premature deaths."
Dr. Fazel and his colleagues’ study was funded by grants from the Wellcome Trust, the Swedish Prison and Probation Service, and the Swedish Research Council. None of its authors declared conflicts of interest. Dr. Robinson disclosed no conflicts of interest related to his editorial.
People who survive a traumatic brain injury are three times more likely to die prematurely than are those who have not, according to results from a large population-based study.
The study, which drew from more than 4 decades of data from Swedish national patient registries and death records, also found that nearly half of the TBI patients who died prematurely died from suicide, violence, or injuries.
For their research, published online Jan. 15 (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2013.3935]), investigators, led by Dr. Seena Fazel of Oxford (England) University, evaluated data from 218,300 men and women who had survived for 6 months or more after TBI with age and sex-matched controls (n = 2,163,190).
Of all the TBI patients, 69.3% were men, 80.5% were not married, and 9.3% had preexisting psychiatric disorders, including 4.4% with substance abuse diagnoses.
Dr. Fazel and his colleagues found that the TBI patients saw a threefold higher mortality before age 56 years, compared with controls, even after researchers adjusted for socioeconomic confounders (adjusted odds ratio, 3.2; 95% confidence interval, 3.0-3.4). Of those who died early, the median age was 18.6 years at the time of the TBI and 40.6 years at death.
The study also looked at unaffected siblings of the TBI patients (n = 150,513) and found significantly greater odds of premature death in the TBI group, compared with their siblings (OR, 2.6; 95% CI, 2.3-2.8). Still, the difference was less than that seen with the general population controls, suggesting that some genetic and environmental factors might be partly responsible for the higher mortality.
The rate of premature deaths among the TBI survivors was low overall, but it was higher among those with psychiatric or substance abuse diagnoses. Mortality from suicide, injuries, and assault was significantly higher in the TBI group than the control group, accounting for 48.6% of premature deaths among TBI patients.
Dr. Fazel and his colleagues wrote in their analysis that in light of these findings, clinical guidelines might need to be revised to focus on preventing mortality beyond the first few months after injury and address high rates of psychiatric comorbidity and substance abuse among TBI patients.
In an editorial accompanying Dr. Fazel and his colleagues’ article, Dr. Robert G. Robinson of the department of psychiatry administration at the University of Iowa in Iowa City, proposed that some of the excess mortality seen among the TBI patients might be attributable to personality – something the study authors also acknowledged as a potential confounder (JAMA Psychiatry 2014 Jan. 15 [doi:10.1001/jamapsychiatry.2013.4241]).
"The preponderance of premature deaths due to external factors suggests that one of the most likely explanations for the findings in the current study is the existence of personality characteristics of impulsiveness, risk-taking behaviors, and proneness to substance abuse. These patients incur a TBI and continue to demonstrate these behaviors after the TBI, which ultimately leads to a fatality," Dr. Robinson wrote.
Dr. Robinson, echoing the recommendations of Dr. Fazel and his colleagues, argued that recognizing such patients is important "because half of these deaths are due to preventable behaviors." Some prevention strategies, he wrote, might include screening TBI patients at discharge for personality characteristics and treating those with the most impulsive risk-taking traits, or administering antidepressants to those seen as vulnerable to depression.
The study authors and Dr. Robinson noted among the study’s strengths of its very large sample size, making it the largest of its kind to date, its long follow-up, and its use of sibling controls. One weakness noted by Dr. Robinson was that the cause of the TBI could not be specified in most cases and that the severity of TBI could only be quantified in some cases by duration of hospitalization.
Because pathologic features, symptoms, and the course of TBI can differ depending on the cause or severity of the injury, Dr. Robinson wrote, "further studies in this area should focus on whether the cause of brain injury, type of brain injury, severity of injury, or premorbid personality characteristics are associated with the highest risk of premature deaths."
Dr. Fazel and his colleagues’ study was funded by grants from the Wellcome Trust, the Swedish Prison and Probation Service, and the Swedish Research Council. None of its authors declared conflicts of interest. Dr. Robinson disclosed no conflicts of interest related to his editorial.
FROM JAMA PSYCHIATRY
Major finding: TBI patients saw higher mortality before age 56 years, compared with controls, even after adjustment for socioeconomic confounders (adjusted OR, 3.2; 95% CI, 3-3.4). Of those who died early, the median age was 18.6 years at the time of the TBI and 40.6 years at death.
Data source: About 2.5 million patient records from Swedish national registries between 1959-2009.
Disclosures: Dr. Fazel and his colleagues’ study was funded by grants from the Wellcome Trust, the Swedish Prison and Probation Service, and the Swedish Research Council. None of its authors declared conflicts of interest. Dr. Robinson disclosed no conflicts of interest related to his editorial.
