Jennie Smith

About 70% of children diagnosed with attention-deficit/hyperactivity disorder before age 7 retained their ADHD diagnoses several years later, with more baseline symptoms, a parental history of psychiatric disorders, and lower socioeconomic status seen as significant predictors of diagnostic stability over time, a cohort study showed.

In this study led by Dr. Evelyn C. Law of Boston Children’s Hospital, 120 children aged 3 years to 6 years 11 months were diagnosed at a hospital-affiliated behavioral clinic using rigorous ADHD criteria; 73% of the cohort were followed up at a mean of 7 years after their diagnosis. Families were interviewed during follow-up to obtain information on family psychiatric history and socioeconomic status, in the study published online March 17 (Pediatrics 2014;133:1-9 [doi:10.1542/peds.2013-3433]).

The researchers found elevated externalizing symptoms and elevated internalizing symptoms at baseline to be statistically significant predictors of a later ADHD diagnosis. Significant family predictors were a parental history of psychopathology and a lower income-to-needs ratio. Of the children who did not meet criteria for ADHD at follow up, more than half were found to have other developmental or behavioral diagnoses including anxiety, autism spectrum disorder, or learning disorders. However, some children who did not meet criteria for ADHD at follow-up did not have other diagnoses, suggesting remittance of ADHD.

Dr. Law and colleagues acknowledged as limitations of their study that the findings were drawn from a single clinic, that follow-up was not possible for a quarter of the cohort, and that patients’ family incomes were higher on average than for the general population.

However, they said, the study has important implications for clinicians caring for young children with ADHD symptoms. The preschool years are a "sensitive period for intervention," Dr. Law and colleagues said, and clinicians should be equipped to monitor learning, behavioral, and mood difficulties over time.

Children with ADHD diagnoses before age 7 should be reevaluated during their primary school years, and family factors "should be explored more explicitly in clinical settings," the researchers wrote, adding that clinicians should consider parent training programs –something already recommended for preschool-age ADHD children by the American Academy of Pediatrics – as potentially helpful in improving outcomes (Pediatrics 2011;128:1007-22).

Dr. Law and colleagues’ study was funded by the National Institutes of Health, and none of its authors disclosed conflicts of interest.

About 70% of children diagnosed with attention-deficit/hyperactivity disorder before age 7 retained their ADHD diagnoses several years later, with more baseline symptoms, a parental history of psychiatric disorders, and lower socioeconomic status seen as significant predictors of diagnostic stability over time, a cohort study showed.

In this study led by Dr. Evelyn C. Law of Boston Children’s Hospital, 120 children aged 3 years to 6 years 11 months were diagnosed at a hospital-affiliated behavioral clinic using rigorous ADHD criteria; 73% of the cohort were followed up at a mean of 7 years after their diagnosis. Families were interviewed during follow-up to obtain information on family psychiatric history and socioeconomic status, in the study published online March 17 (Pediatrics 2014;133:1-9 [doi:10.1542/peds.2013-3433]).

The researchers found elevated externalizing symptoms and elevated internalizing symptoms at baseline to be statistically significant predictors of a later ADHD diagnosis. Significant family predictors were a parental history of psychopathology and a lower income-to-needs ratio. Of the children who did not meet criteria for ADHD at follow up, more than half were found to have other developmental or behavioral diagnoses including anxiety, autism spectrum disorder, or learning disorders. However, some children who did not meet criteria for ADHD at follow-up did not have other diagnoses, suggesting remittance of ADHD.

Dr. Law and colleagues acknowledged as limitations of their study that the findings were drawn from a single clinic, that follow-up was not possible for a quarter of the cohort, and that patients’ family incomes were higher on average than for the general population.

However, they said, the study has important implications for clinicians caring for young children with ADHD symptoms. The preschool years are a "sensitive period for intervention," Dr. Law and colleagues said, and clinicians should be equipped to monitor learning, behavioral, and mood difficulties over time.

Children with ADHD diagnoses before age 7 should be reevaluated during their primary school years, and family factors "should be explored more explicitly in clinical settings," the researchers wrote, adding that clinicians should consider parent training programs –something already recommended for preschool-age ADHD children by the American Academy of Pediatrics – as potentially helpful in improving outcomes (Pediatrics 2011;128:1007-22).

Dr. Law and colleagues’ study was funded by the National Institutes of Health, and none of its authors disclosed conflicts of interest.

About 70% of children diagnosed with attention-deficit/hyperactivity disorder before age 7 retained their ADHD diagnoses several years later, with more baseline symptoms, a parental history of psychiatric disorders, and lower socioeconomic status seen as significant predictors of diagnostic stability over time, a cohort study showed.

In this study led by Dr. Evelyn C. Law of Boston Children’s Hospital, 120 children aged 3 years to 6 years 11 months were diagnosed at a hospital-affiliated behavioral clinic using rigorous ADHD criteria; 73% of the cohort were followed up at a mean of 7 years after their diagnosis. Families were interviewed during follow-up to obtain information on family psychiatric history and socioeconomic status, in the study published online March 17 (Pediatrics 2014;133:1-9 [doi:10.1542/peds.2013-3433]).

The researchers found elevated externalizing symptoms and elevated internalizing symptoms at baseline to be statistically significant predictors of a later ADHD diagnosis. Significant family predictors were a parental history of psychopathology and a lower income-to-needs ratio. Of the children who did not meet criteria for ADHD at follow up, more than half were found to have other developmental or behavioral diagnoses including anxiety, autism spectrum disorder, or learning disorders. However, some children who did not meet criteria for ADHD at follow-up did not have other diagnoses, suggesting remittance of ADHD.

Dr. Law and colleagues acknowledged as limitations of their study that the findings were drawn from a single clinic, that follow-up was not possible for a quarter of the cohort, and that patients’ family incomes were higher on average than for the general population.

However, they said, the study has important implications for clinicians caring for young children with ADHD symptoms. The preschool years are a "sensitive period for intervention," Dr. Law and colleagues said, and clinicians should be equipped to monitor learning, behavioral, and mood difficulties over time.

Children with ADHD diagnoses before age 7 should be reevaluated during their primary school years, and family factors "should be explored more explicitly in clinical settings," the researchers wrote, adding that clinicians should consider parent training programs –something already recommended for preschool-age ADHD children by the American Academy of Pediatrics – as potentially helpful in improving outcomes (Pediatrics 2011;128:1007-22).

Dr. Law and colleagues’ study was funded by the National Institutes of Health, and none of its authors disclosed conflicts of interest.

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.

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.

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

©toranico/thinkstockphotos.com

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.

©toranico/thinkstockphotos.com

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.

©toranico/thinkstockphotos.com

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.

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.

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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]).

© Micah Young/istockphoto.com

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]).

© Micah Young/istockphoto.com

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]).

© Micah Young/istockphoto.com

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.