CHICAGO – A single intra-articular injection of a novel drug known for now as SMO4690 resulted in statistically significant and clinically meaningful improvements in pain and physical function through 6 months of follow-up in a phase 2b study including 695 patients with moderately to severely symptomatic knee OA, Yusuf Yazici, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

Based on the encouraging results of this and another large phase 2 study, two pivotal phase 3, randomized clinical trials are due to start in the spring of 2019. If the results are positive, SMO4690 could become the first approved disease-modifying OA drug (DMOAD), something that’s been a long-sought, high-priority goal in rheumatology, noted Dr. Yazici, chief medical officer at San Diego–based Samumed, which is developing the drug, and a rheumatologist at New York University.

SMO4690 is a small molecule inhibitor of the Wnt signaling pathway. The drug has two distinct mechanisms of action for treatment of knee OA: It has an anti-inflammatory effect and it protects cartilage from degeneration, as demonstrated by a clinically significant improvement in joint space width by x-ray, compared with placebo at 12 months of follow-up after a single baseline injection in the earlier 455-patient, phase 2 study. Also, animal studies suggest SMO4690 generates cartilage, an exciting possibility now being evaluated in two ongoing serial MRI studies in knee OA patients.

Dr. Yazici presented patient-reported outcomes from the 695-patient, 24-week, multicenter, randomized, placebo-controlled, double-blind, phase 2b study, which evaluated four different concentrations of SMO4690. The 0.07- and 0.23-mg per 2-mL injection doses proved significantly better than placebo at 12 weeks – the primary endpoint – for all patient-reported outcomes.

The 0.23-mg dose of SMO4690 remained superior to placebo for all four patient-reported outcomes at subsequent assessments at weeks 16, 20, and 24. The 0.07-mg dose remained significantly better than placebo through week 20.

As in the earlier phase 2 study, SMO4690 raised no significant safety concerns. Adverse events were similar in type and frequency in the active-treatment and placebo groups.

The study was sponsored by Samumed, where Dr. Yazici is employed as chief medical officer.

[email protected]

SOURCE: Yazici Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L03.

CHICAGO – A single intra-articular injection of a novel drug known for now as SMO4690 resulted in statistically significant and clinically meaningful improvements in pain and physical function through 6 months of follow-up in a phase 2b study including 695 patients with moderately to severely symptomatic knee OA, Yusuf Yazici, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

Based on the encouraging results of this and another large phase 2 study, two pivotal phase 3, randomized clinical trials are due to start in the spring of 2019. If the results are positive, SMO4690 could become the first approved disease-modifying OA drug (DMOAD), something that’s been a long-sought, high-priority goal in rheumatology, noted Dr. Yazici, chief medical officer at San Diego–based Samumed, which is developing the drug, and a rheumatologist at New York University.

SMO4690 is a small molecule inhibitor of the Wnt signaling pathway. The drug has two distinct mechanisms of action for treatment of knee OA: It has an anti-inflammatory effect and it protects cartilage from degeneration, as demonstrated by a clinically significant improvement in joint space width by x-ray, compared with placebo at 12 months of follow-up after a single baseline injection in the earlier 455-patient, phase 2 study. Also, animal studies suggest SMO4690 generates cartilage, an exciting possibility now being evaluated in two ongoing serial MRI studies in knee OA patients.

Dr. Yazici presented patient-reported outcomes from the 695-patient, 24-week, multicenter, randomized, placebo-controlled, double-blind, phase 2b study, which evaluated four different concentrations of SMO4690. The 0.07- and 0.23-mg per 2-mL injection doses proved significantly better than placebo at 12 weeks – the primary endpoint – for all patient-reported outcomes.

The 0.23-mg dose of SMO4690 remained superior to placebo for all four patient-reported outcomes at subsequent assessments at weeks 16, 20, and 24. The 0.07-mg dose remained significantly better than placebo through week 20.

As in the earlier phase 2 study, SMO4690 raised no significant safety concerns. Adverse events were similar in type and frequency in the active-treatment and placebo groups.

The study was sponsored by Samumed, where Dr. Yazici is employed as chief medical officer.

[email protected]

SOURCE: Yazici Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L03.

CHICAGO – A single intra-articular injection of a novel drug known for now as SMO4690 resulted in statistically significant and clinically meaningful improvements in pain and physical function through 6 months of follow-up in a phase 2b study including 695 patients with moderately to severely symptomatic knee OA, Yusuf Yazici, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

Based on the encouraging results of this and another large phase 2 study, two pivotal phase 3, randomized clinical trials are due to start in the spring of 2019. If the results are positive, SMO4690 could become the first approved disease-modifying OA drug (DMOAD), something that’s been a long-sought, high-priority goal in rheumatology, noted Dr. Yazici, chief medical officer at San Diego–based Samumed, which is developing the drug, and a rheumatologist at New York University.

SMO4690 is a small molecule inhibitor of the Wnt signaling pathway. The drug has two distinct mechanisms of action for treatment of knee OA: It has an anti-inflammatory effect and it protects cartilage from degeneration, as demonstrated by a clinically significant improvement in joint space width by x-ray, compared with placebo at 12 months of follow-up after a single baseline injection in the earlier 455-patient, phase 2 study. Also, animal studies suggest SMO4690 generates cartilage, an exciting possibility now being evaluated in two ongoing serial MRI studies in knee OA patients.

Dr. Yazici presented patient-reported outcomes from the 695-patient, 24-week, multicenter, randomized, placebo-controlled, double-blind, phase 2b study, which evaluated four different concentrations of SMO4690. The 0.07- and 0.23-mg per 2-mL injection doses proved significantly better than placebo at 12 weeks – the primary endpoint – for all patient-reported outcomes.

The 0.23-mg dose of SMO4690 remained superior to placebo for all four patient-reported outcomes at subsequent assessments at weeks 16, 20, and 24. The 0.07-mg dose remained significantly better than placebo through week 20.

As in the earlier phase 2 study, SMO4690 raised no significant safety concerns. Adverse events were similar in type and frequency in the active-treatment and placebo groups.

The study was sponsored by Samumed, where Dr. Yazici is employed as chief medical officer.

[email protected]

SOURCE: Yazici Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L03.

Given its limited systemic toxicity, topical anthralin is an acceptable second-line treatment option for pediatric alopecia areata (AA), according to Sean Z. Wu, MD, of the department of dermatology, University of Cincinnati, and his associates.

In a retrospective study of 37 pediatric patients with AA, published in Pediatric Dermatology, Dr. Wu and his colleagues found that almost two-thirds experienced at least 50% regrowth of hair with topical anthralin treatment, but they described severe dermatitis and relapses as “potential drawbacks” of treatment.

The 37 patients were in the Cleveland Clinic AA areata database and began treatment with anthralin between 2004 and 2015, at aged 2-17 years (mean age 9). Over half (22) were females and most (31) were white. About 65% had patchy AA; the remainder had either alopecia totalis or alopecia universalis. Prior treatments included topical corticosteroids, minoxidil, and intralesional corticosteroids; four patients had not been treated previously. Patients were followed up from 51 days to more than 10 years, with a mean duration of 2.5 years. Treatment regimens, titrated up to achieve a mild to moderate dermatitis, included application of 0.5% cream for 5 minutes twice a week up to 1.0% cream for 30 minutes a day.

With topical anthralin, 12 (32%) of patients had complete scalp regrowth, 25 (68%) experienced at least 50% regrowth, and 5 (14%) had no response; in five patients, no follow-up information was available. Among those with at least 50% regrowth, the initial response was first noted at a mean of 3.4 months, and the mean time to maximal response was 15 months. This timeline suggests that treatment with anthralin should be continued beyond 1 year to ensure maximum beneficial results with hair regrowth, the authors wrote.

Factors associated with a positive response to treatment included less than 50% of scalp involvement. The two patients who used anthralin as monotherapy did not achieve a 50% scalp response, but the four treatment-naive patients were among those with at least 50% scalp regrowth, versus three of the five patients (60%) who had been treated previously with systemic steroids.

Two potential clinical limitations were noted during the study. Four patients had to stop treatment because of dermatitis, which suggests that patients and parents should be counseled about the potential for severe skin irritation with this treatment, the authors said. And among those who achieved at least 50% scalp regrowth, 16 of the 25 (64%) relapsed. The authors speculated that the effects of the drug could be temporary “or that the disease process may be able to overcome the anthralin effect over time.”

Dr. Wu and his coauthors cited the retrospective design and the small population size as major limitations of the study. Because some patients continued other treatments, it is “difficult to attribute scalp regrowth entirely to anthralin,” and variations in formulation and in treatment regimens are also factors to be considered, they cautioned. That AA has been found to spontaneously resolve, depending upon the severity of the disease, presents additional challenges for clinicians attempting to determine the extent to which anthralin offers therapeutic benefit, they pointed out.

In spite of the drug’s limitations, the authors concluded that the treatment was a safe and useful option as an “adjunct for those who fail first-line therapy with topical or intralesional corticosteroids.” They added that more work is needed to tailor treatment formulation, frequency, and duration to the specific needs of pediatric patients.

The authors had no relevant financial disclosures to report.

SOURCE: Wu SZ et al. Pediatr Dermatol. 2018;35:817-20.

Given its limited systemic toxicity, topical anthralin is an acceptable second-line treatment option for pediatric alopecia areata (AA), according to Sean Z. Wu, MD, of the department of dermatology, University of Cincinnati, and his associates.

In a retrospective study of 37 pediatric patients with AA, published in Pediatric Dermatology, Dr. Wu and his colleagues found that almost two-thirds experienced at least 50% regrowth of hair with topical anthralin treatment, but they described severe dermatitis and relapses as “potential drawbacks” of treatment.

The 37 patients were in the Cleveland Clinic AA areata database and began treatment with anthralin between 2004 and 2015, at aged 2-17 years (mean age 9). Over half (22) were females and most (31) were white. About 65% had patchy AA; the remainder had either alopecia totalis or alopecia universalis. Prior treatments included topical corticosteroids, minoxidil, and intralesional corticosteroids; four patients had not been treated previously. Patients were followed up from 51 days to more than 10 years, with a mean duration of 2.5 years. Treatment regimens, titrated up to achieve a mild to moderate dermatitis, included application of 0.5% cream for 5 minutes twice a week up to 1.0% cream for 30 minutes a day.

With topical anthralin, 12 (32%) of patients had complete scalp regrowth, 25 (68%) experienced at least 50% regrowth, and 5 (14%) had no response; in five patients, no follow-up information was available. Among those with at least 50% regrowth, the initial response was first noted at a mean of 3.4 months, and the mean time to maximal response was 15 months. This timeline suggests that treatment with anthralin should be continued beyond 1 year to ensure maximum beneficial results with hair regrowth, the authors wrote.

Factors associated with a positive response to treatment included less than 50% of scalp involvement. The two patients who used anthralin as monotherapy did not achieve a 50% scalp response, but the four treatment-naive patients were among those with at least 50% scalp regrowth, versus three of the five patients (60%) who had been treated previously with systemic steroids.

Two potential clinical limitations were noted during the study. Four patients had to stop treatment because of dermatitis, which suggests that patients and parents should be counseled about the potential for severe skin irritation with this treatment, the authors said. And among those who achieved at least 50% scalp regrowth, 16 of the 25 (64%) relapsed. The authors speculated that the effects of the drug could be temporary “or that the disease process may be able to overcome the anthralin effect over time.”

Dr. Wu and his coauthors cited the retrospective design and the small population size as major limitations of the study. Because some patients continued other treatments, it is “difficult to attribute scalp regrowth entirely to anthralin,” and variations in formulation and in treatment regimens are also factors to be considered, they cautioned. That AA has been found to spontaneously resolve, depending upon the severity of the disease, presents additional challenges for clinicians attempting to determine the extent to which anthralin offers therapeutic benefit, they pointed out.

In spite of the drug’s limitations, the authors concluded that the treatment was a safe and useful option as an “adjunct for those who fail first-line therapy with topical or intralesional corticosteroids.” They added that more work is needed to tailor treatment formulation, frequency, and duration to the specific needs of pediatric patients.

The authors had no relevant financial disclosures to report.

SOURCE: Wu SZ et al. Pediatr Dermatol. 2018;35:817-20.

Given its limited systemic toxicity, topical anthralin is an acceptable second-line treatment option for pediatric alopecia areata (AA), according to Sean Z. Wu, MD, of the department of dermatology, University of Cincinnati, and his associates.

In a retrospective study of 37 pediatric patients with AA, published in Pediatric Dermatology, Dr. Wu and his colleagues found that almost two-thirds experienced at least 50% regrowth of hair with topical anthralin treatment, but they described severe dermatitis and relapses as “potential drawbacks” of treatment.

The 37 patients were in the Cleveland Clinic AA areata database and began treatment with anthralin between 2004 and 2015, at aged 2-17 years (mean age 9). Over half (22) were females and most (31) were white. About 65% had patchy AA; the remainder had either alopecia totalis or alopecia universalis. Prior treatments included topical corticosteroids, minoxidil, and intralesional corticosteroids; four patients had not been treated previously. Patients were followed up from 51 days to more than 10 years, with a mean duration of 2.5 years. Treatment regimens, titrated up to achieve a mild to moderate dermatitis, included application of 0.5% cream for 5 minutes twice a week up to 1.0% cream for 30 minutes a day.

With topical anthralin, 12 (32%) of patients had complete scalp regrowth, 25 (68%) experienced at least 50% regrowth, and 5 (14%) had no response; in five patients, no follow-up information was available. Among those with at least 50% regrowth, the initial response was first noted at a mean of 3.4 months, and the mean time to maximal response was 15 months. This timeline suggests that treatment with anthralin should be continued beyond 1 year to ensure maximum beneficial results with hair regrowth, the authors wrote.

Factors associated with a positive response to treatment included less than 50% of scalp involvement. The two patients who used anthralin as monotherapy did not achieve a 50% scalp response, but the four treatment-naive patients were among those with at least 50% scalp regrowth, versus three of the five patients (60%) who had been treated previously with systemic steroids.

Two potential clinical limitations were noted during the study. Four patients had to stop treatment because of dermatitis, which suggests that patients and parents should be counseled about the potential for severe skin irritation with this treatment, the authors said. And among those who achieved at least 50% scalp regrowth, 16 of the 25 (64%) relapsed. The authors speculated that the effects of the drug could be temporary “or that the disease process may be able to overcome the anthralin effect over time.”

Dr. Wu and his coauthors cited the retrospective design and the small population size as major limitations of the study. Because some patients continued other treatments, it is “difficult to attribute scalp regrowth entirely to anthralin,” and variations in formulation and in treatment regimens are also factors to be considered, they cautioned. That AA has been found to spontaneously resolve, depending upon the severity of the disease, presents additional challenges for clinicians attempting to determine the extent to which anthralin offers therapeutic benefit, they pointed out.

In spite of the drug’s limitations, the authors concluded that the treatment was a safe and useful option as an “adjunct for those who fail first-line therapy with topical or intralesional corticosteroids.” They added that more work is needed to tailor treatment formulation, frequency, and duration to the specific needs of pediatric patients.

The authors had no relevant financial disclosures to report.

SOURCE: Wu SZ et al. Pediatr Dermatol. 2018;35:817-20.

Infant mortality in the United Sates dropped very slightly from 2015 to 2016 and has not changed significantly since 2011, according to the National Center for Health Statistics.

Overall infant mortality was 5.87 per 1,000 live births in 2016, which was not significantly less than the 2015 rate of 5.90 per 1,000 or the rate of 6.07 per 1,000 recorded in 2011, the NCHS said in a recent Data Brief. The rate for 2016 works out to 3.88 per 1,000 for the neonatal period (0-27 days) and 1.99 per 1,000 during the postneonatal period (28-364 days).

Maternal age had a significant effect on infant mortality in 2016. The rate was lowest for mothers aged 30-34 years (4.86 per 1,000) and highest for those under 20 years (8.69). All overall rates by maternal age were significantly different from each other, except for those of mothers aged 20-24 years (7.13) and those aged 40 years and over (7.27). Neonatal mortality was highest for the under-20 group and the 40-and-over group at 5.32 per 1,000, with the difference between them coming during the postneonatal period: 3.36 for those under 20 and 1.95 for the 40-and-overs, the NCHS investigators reported based on data from the National Vital Statistics System.

The leading cause of death during the neonatal period in 2016 was low birth weight at 98 per 1,000 live births, with congenital malformations second at 86 per 1,000. The leading cause of death in the postneonatal period was congenital malformations at 36 per 1,000, followed by sudden infant death syndrome (35 per 1,000), unintentional injuries (27 per 1,000), diseases of the circulatory system (9 per 1,000), and homicide (6 per 1,000), they added.

[email protected]

Infant mortality in the United Sates dropped very slightly from 2015 to 2016 and has not changed significantly since 2011, according to the National Center for Health Statistics.

Overall infant mortality was 5.87 per 1,000 live births in 2016, which was not significantly less than the 2015 rate of 5.90 per 1,000 or the rate of 6.07 per 1,000 recorded in 2011, the NCHS said in a recent Data Brief. The rate for 2016 works out to 3.88 per 1,000 for the neonatal period (0-27 days) and 1.99 per 1,000 during the postneonatal period (28-364 days).

Maternal age had a significant effect on infant mortality in 2016. The rate was lowest for mothers aged 30-34 years (4.86 per 1,000) and highest for those under 20 years (8.69). All overall rates by maternal age were significantly different from each other, except for those of mothers aged 20-24 years (7.13) and those aged 40 years and over (7.27). Neonatal mortality was highest for the under-20 group and the 40-and-over group at 5.32 per 1,000, with the difference between them coming during the postneonatal period: 3.36 for those under 20 and 1.95 for the 40-and-overs, the NCHS investigators reported based on data from the National Vital Statistics System.

The leading cause of death during the neonatal period in 2016 was low birth weight at 98 per 1,000 live births, with congenital malformations second at 86 per 1,000. The leading cause of death in the postneonatal period was congenital malformations at 36 per 1,000, followed by sudden infant death syndrome (35 per 1,000), unintentional injuries (27 per 1,000), diseases of the circulatory system (9 per 1,000), and homicide (6 per 1,000), they added.

[email protected]

Infant mortality in the United Sates dropped very slightly from 2015 to 2016 and has not changed significantly since 2011, according to the National Center for Health Statistics.

Overall infant mortality was 5.87 per 1,000 live births in 2016, which was not significantly less than the 2015 rate of 5.90 per 1,000 or the rate of 6.07 per 1,000 recorded in 2011, the NCHS said in a recent Data Brief. The rate for 2016 works out to 3.88 per 1,000 for the neonatal period (0-27 days) and 1.99 per 1,000 during the postneonatal period (28-364 days).

Maternal age had a significant effect on infant mortality in 2016. The rate was lowest for mothers aged 30-34 years (4.86 per 1,000) and highest for those under 20 years (8.69). All overall rates by maternal age were significantly different from each other, except for those of mothers aged 20-24 years (7.13) and those aged 40 years and over (7.27). Neonatal mortality was highest for the under-20 group and the 40-and-over group at 5.32 per 1,000, with the difference between them coming during the postneonatal period: 3.36 for those under 20 and 1.95 for the 40-and-overs, the NCHS investigators reported based on data from the National Vital Statistics System.

The leading cause of death during the neonatal period in 2016 was low birth weight at 98 per 1,000 live births, with congenital malformations second at 86 per 1,000. The leading cause of death in the postneonatal period was congenital malformations at 36 per 1,000, followed by sudden infant death syndrome (35 per 1,000), unintentional injuries (27 per 1,000), diseases of the circulatory system (9 per 1,000), and homicide (6 per 1,000), they added.

[email protected]

Using data from the Million Veteran Program (MVP), researchers found people with mutations for PDE3B, PCSK9, and ANGPTL4 had better cholesterol and triglyceride levels than did those without the mutations.

The PDE3B mutation seems to protect against heart disease. A PCSK9 mutation may reduce the risk not only of heart disease, but also abdominal aortic aneurysm. The ANGPTL4 mutation was linked to lower risk of type 2 DM.

MVP, 1 of the world’s largest databases of health and genomic information, partners with veterans receiving care in the VHA to study how genes affect health. It has enrolled > 700,000 veterans to date.

Using data from the Million Veteran Program (MVP), researchers found people with mutations for PDE3B, PCSK9, and ANGPTL4 had better cholesterol and triglyceride levels than did those without the mutations.

The PDE3B mutation seems to protect against heart disease. A PCSK9 mutation may reduce the risk not only of heart disease, but also abdominal aortic aneurysm. The ANGPTL4 mutation was linked to lower risk of type 2 DM.

MVP, 1 of the world’s largest databases of health and genomic information, partners with veterans receiving care in the VHA to study how genes affect health. It has enrolled > 700,000 veterans to date.

Using data from the Million Veteran Program (MVP), researchers found people with mutations for PDE3B, PCSK9, and ANGPTL4 had better cholesterol and triglyceride levels than did those without the mutations.

The PDE3B mutation seems to protect against heart disease. A PCSK9 mutation may reduce the risk not only of heart disease, but also abdominal aortic aneurysm. The ANGPTL4 mutation was linked to lower risk of type 2 DM.

MVP, 1 of the world’s largest databases of health and genomic information, partners with veterans receiving care in the VHA to study how genes affect health. It has enrolled > 700,000 veterans to date.

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Astellas Pharma

The U.S. Food and Drug Administration (FDA) has approved gilteritinib (Xospata) for use in adults who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, as detected by an FDA-approved test.

The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib.

The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect FLT3 mutations in patients with AML.

Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain.

The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939).

The trial enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835, or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.

Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit.

Efficacy results are available for 138 patients, with a median follow-up of 4.6 months (range, 2.8 to 15.8).

The complete response (CR) rate was 11.6% (16/138), the rate of CR with partial hematologic recovery (CRh) was 9.4% (13/138), and the rate of CR/CRh was 21% (29/138).

The median duration of CR/CRh was 4.6 months.

There were 106 patients who were transfusion-dependent at baseline, and 33 of these patients (31.1%) became transfusion-independent during the post-baseline period.

Seventeen of the 32 patients (53.1%) who were transfusion-independent at baseline remained transfusion-independent.

Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months (range, 0.1 to 42.8).

The most common adverse events were myalgia/arthralgia (42%), transaminase increase (41%), fatigue/malaise (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), constipation (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

Eight percent of patients (n=22) discontinued gilteritinib due to adverse events. The most common were pneumonia (2%), sepsis (2%), and dyspnea (1%).

For more details on the ADMIRAL trial and gilteritinib, see the full prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

Specifically, Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL.

Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy.

And Truxima is approved as a single agent to treat non-progressing, low-grade, CD20­-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.

The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

A phase 3 trial recently published in The Lancet Haematology suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma.

For more details on Truxima, see the prescribing information.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.

Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.

The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.

The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.

Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.

Study design

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.

In part B, researchers evaluated damoctocog alfa pegol for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

Efficacy

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.

Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

ORLANDO – More stringent gun laws are linked to reduced firearm-related pediatric injury and mortality, and laws restricting children’s access to firearms are linked to reduced pediatric firearm suicide rates, according to research.

Bytmonas/ThinkStock

“State-level legislation could play an important role in reducing pediatric firearm-related deaths,” concluded Jordan S. Taylor, MD, of Stanford (Calif.) University and his colleagues.

Dr. Taylor earned top honors among the American Academy of Pediatrics (AAP) Council on Injury, Violence and Poison Prevention research abstracts when he presented his findings at the annual meeting of the American Academy of Pediatrics.

Firearm injuries account for the second leading cause of death among U.S. children: 3,155 youth ages 19 years and younger died from gunshot injuries in 2016, and more than 17,000 were injured. Yet state laws governing the purchase, ownership, carriage, and storage of guns vary widely across the country. Dr. Taylor and his colleagues conducted two studies to assess the effects of firearm legislation on firearm-related injuries and deaths in U.S. children.

In their first study, they analyzed pediatric inpatient admissions for firearm injuries in 2012 relative to the stringency of state firearm legislation. They relied on five data sources for the analysis: the Kids’ Inpatient Database (KID), the Healthcare Cost and Utilization Project, the Agency for Healthcare Research and Quality, the U.S. Census Bureau, and the 2013 Brady scorecard.

The Brady scorecard provides scores for each state based on the presence and strictness of firearm-related laws, including legislation on background checks, ability of dangerous individuals to purchase guns, trafficking laws, and laws governing the sales, carrying, and purchasing of firearms.

The 10 states with the strictest laws (highest Brady scores) are California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island. The 10 states with the lowest scores (least-strict legislation) are Alaska, Arizona, Arkansas, Florida, Kentucky, Louisiana, Montana, Nevada, Virginia, and Wyoming.

Among the 6,941 youth (aged 0-20 years) hospitalized in 2012 for firearm injuries, 7% died. More than a third of these (36%) occurred in the South, 25% in the Midwest, 22% in the West, and 17% in the Northeast.

Children most likely to be injured were boys, older children, black and Latino children, and children living in low-income zip codes.

The Midwest and South, which have lower average Brady scores (more lax legislation on guns), had 8.30 injuries per 100,000 children, compared with 7.54 injuries per 100,000 children in the Northeast and West, which have higher average Brady scores (more stringent gun laws). This was a difference of 0.76 injuries per 100,000 children (95% confidence interval, 0.38-1.13; P less than 0.001).

Then the researchers conducted a second analysis that looked specifically at firearm mortality within the context of both child access prevention (CAP) laws and states’ Brady scores. CAP laws include safe storage laws and gun lock laws, for example.

This analysis used the Web-Based Injury Statistics Query and Reporting System to capture pediatric firearm deaths from 2014-2015 and compared these to the 2014 Brady scores and CAP laws.

An estimated 2,715 child gun deaths occurred during the study period, of which 62% were homicides and 31% were suicides. The researchers identified “a significant negative correlation between states’ firearm legislation stringency and pediatric firearm mortality (Spearman correlation coefficient = –0.66) and between presence of CAP laws and firearm suicide rates (Spearman correlation coefficient = –0.56).”

Dr. Taylor said in an interview, “states that have both types of child access prevention laws [had] suicide rates four times lower than states that did not have either of those.”

Positive correlations also showed up between unemployment rate and firearm homicide rate (Spearman correlation coefficient = 0.55) and teen tobacco use and firearm suicide rate (Spearman correlation coefficient = 0.50).

The association between Brady scores and pediatric mortality from firearms remained significant after adjustment for poverty, unemployment, and substance abuse (P less than .01). Similarly, the association between the pediatric firearm suicide rate and CAP laws remained significant after controlling for socioeconomic factors and other firearm legislation (P less than .01).

In a video interview, Dr. Taylor discussed his research findings and their importance in clinical practice.

“It’s absolutely important for pediatricians to talk to families about firearms in their home and also in the homes of their friends that they visit,” Dr. Taylor said. “We try to approach it as a public health issue similar to seat belts and car seats.”

No external funding was used, and Dr. Taylor reported no conflicts of interest.

ORLANDO – More stringent gun laws are linked to reduced firearm-related pediatric injury and mortality, and laws restricting children’s access to firearms are linked to reduced pediatric firearm suicide rates, according to research.

Bytmonas/ThinkStock

“State-level legislation could play an important role in reducing pediatric firearm-related deaths,” concluded Jordan S. Taylor, MD, of Stanford (Calif.) University and his colleagues.

Dr. Taylor earned top honors among the American Academy of Pediatrics (AAP) Council on Injury, Violence and Poison Prevention research abstracts when he presented his findings at the annual meeting of the American Academy of Pediatrics.

Firearm injuries account for the second leading cause of death among U.S. children: 3,155 youth ages 19 years and younger died from gunshot injuries in 2016, and more than 17,000 were injured. Yet state laws governing the purchase, ownership, carriage, and storage of guns vary widely across the country. Dr. Taylor and his colleagues conducted two studies to assess the effects of firearm legislation on firearm-related injuries and deaths in U.S. children.

In their first study, they analyzed pediatric inpatient admissions for firearm injuries in 2012 relative to the stringency of state firearm legislation. They relied on five data sources for the analysis: the Kids’ Inpatient Database (KID), the Healthcare Cost and Utilization Project, the Agency for Healthcare Research and Quality, the U.S. Census Bureau, and the 2013 Brady scorecard.

The Brady scorecard provides scores for each state based on the presence and strictness of firearm-related laws, including legislation on background checks, ability of dangerous individuals to purchase guns, trafficking laws, and laws governing the sales, carrying, and purchasing of firearms.

The 10 states with the strictest laws (highest Brady scores) are California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island. The 10 states with the lowest scores (least-strict legislation) are Alaska, Arizona, Arkansas, Florida, Kentucky, Louisiana, Montana, Nevada, Virginia, and Wyoming.

Among the 6,941 youth (aged 0-20 years) hospitalized in 2012 for firearm injuries, 7% died. More than a third of these (36%) occurred in the South, 25% in the Midwest, 22% in the West, and 17% in the Northeast.

Children most likely to be injured were boys, older children, black and Latino children, and children living in low-income zip codes.

The Midwest and South, which have lower average Brady scores (more lax legislation on guns), had 8.30 injuries per 100,000 children, compared with 7.54 injuries per 100,000 children in the Northeast and West, which have higher average Brady scores (more stringent gun laws). This was a difference of 0.76 injuries per 100,000 children (95% confidence interval, 0.38-1.13; P less than 0.001).

Then the researchers conducted a second analysis that looked specifically at firearm mortality within the context of both child access prevention (CAP) laws and states’ Brady scores. CAP laws include safe storage laws and gun lock laws, for example.

This analysis used the Web-Based Injury Statistics Query and Reporting System to capture pediatric firearm deaths from 2014-2015 and compared these to the 2014 Brady scores and CAP laws.

An estimated 2,715 child gun deaths occurred during the study period, of which 62% were homicides and 31% were suicides. The researchers identified “a significant negative correlation between states’ firearm legislation stringency and pediatric firearm mortality (Spearman correlation coefficient = –0.66) and between presence of CAP laws and firearm suicide rates (Spearman correlation coefficient = –0.56).”

Dr. Taylor said in an interview, “states that have both types of child access prevention laws [had] suicide rates four times lower than states that did not have either of those.”

Positive correlations also showed up between unemployment rate and firearm homicide rate (Spearman correlation coefficient = 0.55) and teen tobacco use and firearm suicide rate (Spearman correlation coefficient = 0.50).

The association between Brady scores and pediatric mortality from firearms remained significant after adjustment for poverty, unemployment, and substance abuse (P less than .01). Similarly, the association between the pediatric firearm suicide rate and CAP laws remained significant after controlling for socioeconomic factors and other firearm legislation (P less than .01).

In a video interview, Dr. Taylor discussed his research findings and their importance in clinical practice.

“It’s absolutely important for pediatricians to talk to families about firearms in their home and also in the homes of their friends that they visit,” Dr. Taylor said. “We try to approach it as a public health issue similar to seat belts and car seats.”

No external funding was used, and Dr. Taylor reported no conflicts of interest.

ORLANDO – More stringent gun laws are linked to reduced firearm-related pediatric injury and mortality, and laws restricting children’s access to firearms are linked to reduced pediatric firearm suicide rates, according to research.

Bytmonas/ThinkStock

“State-level legislation could play an important role in reducing pediatric firearm-related deaths,” concluded Jordan S. Taylor, MD, of Stanford (Calif.) University and his colleagues.

Dr. Taylor earned top honors among the American Academy of Pediatrics (AAP) Council on Injury, Violence and Poison Prevention research abstracts when he presented his findings at the annual meeting of the American Academy of Pediatrics.

Firearm injuries account for the second leading cause of death among U.S. children: 3,155 youth ages 19 years and younger died from gunshot injuries in 2016, and more than 17,000 were injured. Yet state laws governing the purchase, ownership, carriage, and storage of guns vary widely across the country. Dr. Taylor and his colleagues conducted two studies to assess the effects of firearm legislation on firearm-related injuries and deaths in U.S. children.

In their first study, they analyzed pediatric inpatient admissions for firearm injuries in 2012 relative to the stringency of state firearm legislation. They relied on five data sources for the analysis: the Kids’ Inpatient Database (KID), the Healthcare Cost and Utilization Project, the Agency for Healthcare Research and Quality, the U.S. Census Bureau, and the 2013 Brady scorecard.

The Brady scorecard provides scores for each state based on the presence and strictness of firearm-related laws, including legislation on background checks, ability of dangerous individuals to purchase guns, trafficking laws, and laws governing the sales, carrying, and purchasing of firearms.

The 10 states with the strictest laws (highest Brady scores) are California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island. The 10 states with the lowest scores (least-strict legislation) are Alaska, Arizona, Arkansas, Florida, Kentucky, Louisiana, Montana, Nevada, Virginia, and Wyoming.

Among the 6,941 youth (aged 0-20 years) hospitalized in 2012 for firearm injuries, 7% died. More than a third of these (36%) occurred in the South, 25% in the Midwest, 22% in the West, and 17% in the Northeast.

Children most likely to be injured were boys, older children, black and Latino children, and children living in low-income zip codes.

The Midwest and South, which have lower average Brady scores (more lax legislation on guns), had 8.30 injuries per 100,000 children, compared with 7.54 injuries per 100,000 children in the Northeast and West, which have higher average Brady scores (more stringent gun laws). This was a difference of 0.76 injuries per 100,000 children (95% confidence interval, 0.38-1.13; P less than 0.001).

Then the researchers conducted a second analysis that looked specifically at firearm mortality within the context of both child access prevention (CAP) laws and states’ Brady scores. CAP laws include safe storage laws and gun lock laws, for example.

This analysis used the Web-Based Injury Statistics Query and Reporting System to capture pediatric firearm deaths from 2014-2015 and compared these to the 2014 Brady scores and CAP laws.

An estimated 2,715 child gun deaths occurred during the study period, of which 62% were homicides and 31% were suicides. The researchers identified “a significant negative correlation between states’ firearm legislation stringency and pediatric firearm mortality (Spearman correlation coefficient = –0.66) and between presence of CAP laws and firearm suicide rates (Spearman correlation coefficient = –0.56).”

Dr. Taylor said in an interview, “states that have both types of child access prevention laws [had] suicide rates four times lower than states that did not have either of those.”

Positive correlations also showed up between unemployment rate and firearm homicide rate (Spearman correlation coefficient = 0.55) and teen tobacco use and firearm suicide rate (Spearman correlation coefficient = 0.50).

The association between Brady scores and pediatric mortality from firearms remained significant after adjustment for poverty, unemployment, and substance abuse (P less than .01). Similarly, the association between the pediatric firearm suicide rate and CAP laws remained significant after controlling for socioeconomic factors and other firearm legislation (P less than .01).

In a video interview, Dr. Taylor discussed his research findings and their importance in clinical practice.

“It’s absolutely important for pediatricians to talk to families about firearms in their home and also in the homes of their friends that they visit,” Dr. Taylor said. “We try to approach it as a public health issue similar to seat belts and car seats.”

No external funding was used, and Dr. Taylor reported no conflicts of interest.

SAN FRANCISCO – Using normothermic machine perfusion (NMP) to preserve steatotic livers may result in more successful transplantation of these organs, especially when used concomitantly with lipid apheresis filtration and defatting agents, results from a small trial showed.

Doug Brunk/MDedge News

“This is important in the context of liver transplantation, because fatty livers do very badly when their time is blunted,” study coauthor Carlo Ceresa, MBChB, MRCS, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “They’re susceptible to ischemia reperfusion injury, and as a result, a large number are discarded. In the U.S., it’s estimated that around 6,000 steatotic livers are discarded each year. In the U.K., the picture is very similar. Because up to 20% of patients die on the waiting list for liver transplant, we need to try to identify methods to use more marginal organs. Unfortunately, with the obesity epidemic and obesity being a risk factor for NAFLD [nonalcoholic fatty liver disease], we find more fatty livers in the donor pool, and we aren’t able to use them. Identifying methods to salvage these livers for transplantation [is] of great importance.”

NMP maintains the liver in a fully functioning state ex situ and provides oxygen and nutrition at 37° C, said Dr. Ceresa, who is a clinical research fellow with the Medical Research Council and a PhD candidate at the University of Oxford, England. In an effort to evaluate the impact of NMP and defatting adjuncts on human steatotic livers, he and his colleagues perfused 18 discarded human steatotic livers on a normothermic, blood-based circuit for 48 hours. Of these, six were perfused by normothermic machine perfusion alone (group 1), while six were perfused by NMP plus apheresis filtration, which removes lipoproteins (group 2). “The hypothesis here was that we could mechanically remove the fat that the liver releases,” he said. The remaining six livers were perfused with NMP, lipid apheresis filtration, and defatting agents including L-carnitine and forskolin (group 3).

The livers in group 1 “did pretty badly,” Dr. Ceresa said. “Their function wasn’t great and within 48 hours deteriorated, and there was a slight increase in liver fat. That’s probably attributable to de novo lipogenesis.” However, the livers in groups 2 and 3 demonstrated a significant reduction in circulating triglycerides and in perfusate total cholesterol by 48 hours, compared with those in group 1. The researchers also observed an increase in median fatty acid oxidation as measured by 3-hydroxybutyrate among the livers in group 3, compared with those in groups 1 and 2. In addition, the livers in group 3 were the only ones to show a mean reduction in tissue triglyceride level.

Dr. Ceresa described the findings as “exciting, because we have a captive organ we can manipulate, which could then result in a successful transplantation,” he said. “You also get to test drive and get an objective assessment of the organ’s function before you transplant it, so the result may be more predictable. It gives us a very useful model to study NAFLD.”

The next step, he said, is to plan a clinical trial to determine if clinical outcomes can be improved through these ex situ interventions on steatotic livers.

Dr. Ceresa reported having no financial disclosures.
 

[email protected]

Source: Hepatology 2018;68[S1], Abstract 3.

SAN FRANCISCO – Using normothermic machine perfusion (NMP) to preserve steatotic livers may result in more successful transplantation of these organs, especially when used concomitantly with lipid apheresis filtration and defatting agents, results from a small trial showed.

Doug Brunk/MDedge News

“This is important in the context of liver transplantation, because fatty livers do very badly when their time is blunted,” study coauthor Carlo Ceresa, MBChB, MRCS, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “They’re susceptible to ischemia reperfusion injury, and as a result, a large number are discarded. In the U.S., it’s estimated that around 6,000 steatotic livers are discarded each year. In the U.K., the picture is very similar. Because up to 20% of patients die on the waiting list for liver transplant, we need to try to identify methods to use more marginal organs. Unfortunately, with the obesity epidemic and obesity being a risk factor for NAFLD [nonalcoholic fatty liver disease], we find more fatty livers in the donor pool, and we aren’t able to use them. Identifying methods to salvage these livers for transplantation [is] of great importance.”

NMP maintains the liver in a fully functioning state ex situ and provides oxygen and nutrition at 37° C, said Dr. Ceresa, who is a clinical research fellow with the Medical Research Council and a PhD candidate at the University of Oxford, England. In an effort to evaluate the impact of NMP and defatting adjuncts on human steatotic livers, he and his colleagues perfused 18 discarded human steatotic livers on a normothermic, blood-based circuit for 48 hours. Of these, six were perfused by normothermic machine perfusion alone (group 1), while six were perfused by NMP plus apheresis filtration, which removes lipoproteins (group 2). “The hypothesis here was that we could mechanically remove the fat that the liver releases,” he said. The remaining six livers were perfused with NMP, lipid apheresis filtration, and defatting agents including L-carnitine and forskolin (group 3).

The livers in group 1 “did pretty badly,” Dr. Ceresa said. “Their function wasn’t great and within 48 hours deteriorated, and there was a slight increase in liver fat. That’s probably attributable to de novo lipogenesis.” However, the livers in groups 2 and 3 demonstrated a significant reduction in circulating triglycerides and in perfusate total cholesterol by 48 hours, compared with those in group 1. The researchers also observed an increase in median fatty acid oxidation as measured by 3-hydroxybutyrate among the livers in group 3, compared with those in groups 1 and 2. In addition, the livers in group 3 were the only ones to show a mean reduction in tissue triglyceride level.

Dr. Ceresa described the findings as “exciting, because we have a captive organ we can manipulate, which could then result in a successful transplantation,” he said. “You also get to test drive and get an objective assessment of the organ’s function before you transplant it, so the result may be more predictable. It gives us a very useful model to study NAFLD.”

The next step, he said, is to plan a clinical trial to determine if clinical outcomes can be improved through these ex situ interventions on steatotic livers.

Dr. Ceresa reported having no financial disclosures.
 

[email protected]

Source: Hepatology 2018;68[S1], Abstract 3.

SAN FRANCISCO – Using normothermic machine perfusion (NMP) to preserve steatotic livers may result in more successful transplantation of these organs, especially when used concomitantly with lipid apheresis filtration and defatting agents, results from a small trial showed.

Doug Brunk/MDedge News

“This is important in the context of liver transplantation, because fatty livers do very badly when their time is blunted,” study coauthor Carlo Ceresa, MBChB, MRCS, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “They’re susceptible to ischemia reperfusion injury, and as a result, a large number are discarded. In the U.S., it’s estimated that around 6,000 steatotic livers are discarded each year. In the U.K., the picture is very similar. Because up to 20% of patients die on the waiting list for liver transplant, we need to try to identify methods to use more marginal organs. Unfortunately, with the obesity epidemic and obesity being a risk factor for NAFLD [nonalcoholic fatty liver disease], we find more fatty livers in the donor pool, and we aren’t able to use them. Identifying methods to salvage these livers for transplantation [is] of great importance.”

NMP maintains the liver in a fully functioning state ex situ and provides oxygen and nutrition at 37° C, said Dr. Ceresa, who is a clinical research fellow with the Medical Research Council and a PhD candidate at the University of Oxford, England. In an effort to evaluate the impact of NMP and defatting adjuncts on human steatotic livers, he and his colleagues perfused 18 discarded human steatotic livers on a normothermic, blood-based circuit for 48 hours. Of these, six were perfused by normothermic machine perfusion alone (group 1), while six were perfused by NMP plus apheresis filtration, which removes lipoproteins (group 2). “The hypothesis here was that we could mechanically remove the fat that the liver releases,” he said. The remaining six livers were perfused with NMP, lipid apheresis filtration, and defatting agents including L-carnitine and forskolin (group 3).

The livers in group 1 “did pretty badly,” Dr. Ceresa said. “Their function wasn’t great and within 48 hours deteriorated, and there was a slight increase in liver fat. That’s probably attributable to de novo lipogenesis.” However, the livers in groups 2 and 3 demonstrated a significant reduction in circulating triglycerides and in perfusate total cholesterol by 48 hours, compared with those in group 1. The researchers also observed an increase in median fatty acid oxidation as measured by 3-hydroxybutyrate among the livers in group 3, compared with those in groups 1 and 2. In addition, the livers in group 3 were the only ones to show a mean reduction in tissue triglyceride level.

Dr. Ceresa described the findings as “exciting, because we have a captive organ we can manipulate, which could then result in a successful transplantation,” he said. “You also get to test drive and get an objective assessment of the organ’s function before you transplant it, so the result may be more predictable. It gives us a very useful model to study NAFLD.”

The next step, he said, is to plan a clinical trial to determine if clinical outcomes can be improved through these ex situ interventions on steatotic livers.

Dr. Ceresa reported having no financial disclosures.
 

[email protected]

Source: Hepatology 2018;68[S1], Abstract 3.