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PCVs reduced CAP hospitalizations in young children but not other age groups
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
FROM VACCINE
Emicizumab reduces bleeds in kids with hemophilia A and inhibitors
ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.
Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.
Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.
The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.
Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.
HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.
Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.
The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.
Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).
Efficacy
The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.
Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.
There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.
A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).
Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.
The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.
There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.
Safety
All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)
There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.
There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.
“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.” 
ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.
Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.
Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.
The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.
Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.
HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.
Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.
The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.
Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).
Efficacy
The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.
Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.
There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.
A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).
Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.
The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.
There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.
Safety
All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)
There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.
There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.
“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.”
ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.
Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.
Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.
The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.
Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.
HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.
Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.
The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.
Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).
Efficacy
The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.
Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.
There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.
A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).
Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.
The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.
There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.
Safety
All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)
There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.
There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.
“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.”
Gene Therapy May Benefit Patients With Cerebral ALD
KANSAS CITY, MO—Lentiviral gene therapy halts inflammation and demyelination in patients with cerebral adrenoleukodystrophy (ALD), according to research presented at the 46th Annual Meeting of the Child Neurology Society and published in the New England Journal of Medicine. The treatment appears to stabilize neurologic function and to have an acceptable safety profile.
ALD is an X-linked genetic disease caused by a defect in ABCD1, which encodes the peroxisomal ABC half-transporter ALD protein. The defect results in abnormal breakdown of very-long-chain fatty acids, which build up and affect tissues in the nervous system. The most common phenotype of ALD is adrenomyeloneuropathy, which involves axonal degeneration in the spinal cord. A more severe phenotype is childhood cerebral adenopathy, which manifests as an inflammatory demyelination in the white matter.
Allogeneic bone marrow transplantation is the only other treatment with proven efficacy in childhood cerebral ALD. It halts disease progression and improves survival in presymptomatic patients. Finding a donor with identical human leukocyte antigen often is difficult, however. In addition, the treatment entails risks of graft failure and graft-versus-host disease, and the rate of treatment-related mortality is greater than 10%. Gene therapy “may be an alternative to allogeneic bone marrow transplantation, particularly for patients who do not have a matched sibling donor who are at risk for graft failure and graft-versus-host [disease],” said Florian Eichler, MD, Director of the Leukodystrophy Service at Massachusetts General Hospital for Children in Boston.
Researchers Transduced Stem Cells Ex Vivo
In the first trial of its kind, Dr. Eichler and colleagues investigated the safety and efficacy of gene therapy with autologous hematopoietic stem cells for cerebral ALD. The enrollment criteria for the phase II–III, single-arm, open-label study were identical to those for conventional bone marrow transplantation, said Dr. Eichler. Eligible participants were age 17 or younger, had a defect in ABCD1, and had evidence of an active, inflammatory lesion on brain MRI. Children with sibling donors for bone marrow transplantation were excluded from the study.
The investigators obtained CD34+ cells from participants through apheresis and transduced them ex vivo with a lentiviral vector containing normal ABCD1. After undergoing conditioning with busulfan and cyclophosphamide, the patients received an infusion of the transduced CD34+ cells. Patients were assessed regularly for graft-versus-host disease, death, and major functional disabilities. Dr. Eichler and colleagues also monitored participants for changes in neurologic function and increases in MRI lesions. At the end of a two-year follow-up period, patients were offered enrollment in a 13-year long-term follow-up study. The main study’s primary end point was being alive and having no major functional disability at 24 months.
Lesion Progression Stabilized in Most Patients
Dr. Eichler and colleagues treated 17 patients with a mean age at enrollment of 6. Participants’ median Loes score at baseline was 2.0, which indicated a low level of neurologic progression. All patients had an ALD neurologic function scale score of 0 at baseline, indicating an absence of clinical signs of cerebral disease.
The vector copy number in peripheral blood ranged from 0.10 to 1.55 in the 14 patients assessed at month 24. At month 36, the number ranged from 0.36 to 1.83 in the three patients assessed. The number had generally stabilized by two months after infusion. The investigators did not observe preferential integration in or near genes that have previously been associated with serious adverse events related to gene therapy (eg, MDS1, EVI1, and LMO2). All participants had expression of ALD protein in peripheral-blood leukocytes at the most recent follow-up (median follow-up time was 29.4 months). The median percentage of CD14+ cells that expressed ALD protein was 19% at 24 months.
Of the 17 patients, 15 were alive at 24 months and maintained an ALD neurologic function scale score of 0 or 1. In untreated patients, ALD neurologic function scale score usually increases significantly after the first symptoms appear. One patient in the study was progressing rapidly at the time of enrollment and subsequently died of disease progression. Another patient with disease progression on MRI withdrew from the study after the infusion and subsequently died from the complications of an allogeneic transplantation
An exploratory analysis indicated that participants with higher vector copy number in their peripheral blood tended to have better neurologic outcomes, while participants with lower vector copy number tended to have poor neurologic outcomes.
Lesion progression, as measured with the Loes score, had stabilized in 12 of the 17 patients (71%) at the time of the interim analysis. “Half the patients stabilized immediately in their Loes scores after treatment. The other half tended to progress within the first 12 months and then stabilize over time,” said Dr. Eichler.
Gadolinium enhancement resolved in 16 of 17 patients by six months. It reappeared in some patients after treatment, although it was much fainter and more poorly circumscribed, compared with the time of screening, said Dr. Eichler.
The investigators did not observe graft failure or graft-versus-host disease in the population. Most adverse events associated with the treatment were consistent with those associated with myeloablative chemotherapy and occurred during conditioning or during the first two weeks after the infusion. One serious adverse event that possibly was related to treatment was hemorrhagic cystitis associated with BK virus, which resolved with conservative measures.
The results have implications for leukodystrophies in general, according to Dr. Eichler. “Specific phenotypes, even within the same individual leukodystrophy, require different approaches” such as ex vivo or in vivo gene therapy, he added. Overall, the safety data are reassuring, and gene therapy appears to have encouraging efficacy in ALD, he concluded.
—Erik Greb
Suggested Reading
Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630-1638.
Engelen M. Optimizing treatment for cerebral adrenoleukodystrophy in the era of gene therapy. N Engl J Med. 2017;377(17):1682-1684.
KANSAS CITY, MO—Lentiviral gene therapy halts inflammation and demyelination in patients with cerebral adrenoleukodystrophy (ALD), according to research presented at the 46th Annual Meeting of the Child Neurology Society and published in the New England Journal of Medicine. The treatment appears to stabilize neurologic function and to have an acceptable safety profile.
ALD is an X-linked genetic disease caused by a defect in ABCD1, which encodes the peroxisomal ABC half-transporter ALD protein. The defect results in abnormal breakdown of very-long-chain fatty acids, which build up and affect tissues in the nervous system. The most common phenotype of ALD is adrenomyeloneuropathy, which involves axonal degeneration in the spinal cord. A more severe phenotype is childhood cerebral adenopathy, which manifests as an inflammatory demyelination in the white matter.
Allogeneic bone marrow transplantation is the only other treatment with proven efficacy in childhood cerebral ALD. It halts disease progression and improves survival in presymptomatic patients. Finding a donor with identical human leukocyte antigen often is difficult, however. In addition, the treatment entails risks of graft failure and graft-versus-host disease, and the rate of treatment-related mortality is greater than 10%. Gene therapy “may be an alternative to allogeneic bone marrow transplantation, particularly for patients who do not have a matched sibling donor who are at risk for graft failure and graft-versus-host [disease],” said Florian Eichler, MD, Director of the Leukodystrophy Service at Massachusetts General Hospital for Children in Boston.
Researchers Transduced Stem Cells Ex Vivo
In the first trial of its kind, Dr. Eichler and colleagues investigated the safety and efficacy of gene therapy with autologous hematopoietic stem cells for cerebral ALD. The enrollment criteria for the phase II–III, single-arm, open-label study were identical to those for conventional bone marrow transplantation, said Dr. Eichler. Eligible participants were age 17 or younger, had a defect in ABCD1, and had evidence of an active, inflammatory lesion on brain MRI. Children with sibling donors for bone marrow transplantation were excluded from the study.
The investigators obtained CD34+ cells from participants through apheresis and transduced them ex vivo with a lentiviral vector containing normal ABCD1. After undergoing conditioning with busulfan and cyclophosphamide, the patients received an infusion of the transduced CD34+ cells. Patients were assessed regularly for graft-versus-host disease, death, and major functional disabilities. Dr. Eichler and colleagues also monitored participants for changes in neurologic function and increases in MRI lesions. At the end of a two-year follow-up period, patients were offered enrollment in a 13-year long-term follow-up study. The main study’s primary end point was being alive and having no major functional disability at 24 months.
Lesion Progression Stabilized in Most Patients
Dr. Eichler and colleagues treated 17 patients with a mean age at enrollment of 6. Participants’ median Loes score at baseline was 2.0, which indicated a low level of neurologic progression. All patients had an ALD neurologic function scale score of 0 at baseline, indicating an absence of clinical signs of cerebral disease.
The vector copy number in peripheral blood ranged from 0.10 to 1.55 in the 14 patients assessed at month 24. At month 36, the number ranged from 0.36 to 1.83 in the three patients assessed. The number had generally stabilized by two months after infusion. The investigators did not observe preferential integration in or near genes that have previously been associated with serious adverse events related to gene therapy (eg, MDS1, EVI1, and LMO2). All participants had expression of ALD protein in peripheral-blood leukocytes at the most recent follow-up (median follow-up time was 29.4 months). The median percentage of CD14+ cells that expressed ALD protein was 19% at 24 months.
Of the 17 patients, 15 were alive at 24 months and maintained an ALD neurologic function scale score of 0 or 1. In untreated patients, ALD neurologic function scale score usually increases significantly after the first symptoms appear. One patient in the study was progressing rapidly at the time of enrollment and subsequently died of disease progression. Another patient with disease progression on MRI withdrew from the study after the infusion and subsequently died from the complications of an allogeneic transplantation
An exploratory analysis indicated that participants with higher vector copy number in their peripheral blood tended to have better neurologic outcomes, while participants with lower vector copy number tended to have poor neurologic outcomes.
Lesion progression, as measured with the Loes score, had stabilized in 12 of the 17 patients (71%) at the time of the interim analysis. “Half the patients stabilized immediately in their Loes scores after treatment. The other half tended to progress within the first 12 months and then stabilize over time,” said Dr. Eichler.
Gadolinium enhancement resolved in 16 of 17 patients by six months. It reappeared in some patients after treatment, although it was much fainter and more poorly circumscribed, compared with the time of screening, said Dr. Eichler.
The investigators did not observe graft failure or graft-versus-host disease in the population. Most adverse events associated with the treatment were consistent with those associated with myeloablative chemotherapy and occurred during conditioning or during the first two weeks after the infusion. One serious adverse event that possibly was related to treatment was hemorrhagic cystitis associated with BK virus, which resolved with conservative measures.
The results have implications for leukodystrophies in general, according to Dr. Eichler. “Specific phenotypes, even within the same individual leukodystrophy, require different approaches” such as ex vivo or in vivo gene therapy, he added. Overall, the safety data are reassuring, and gene therapy appears to have encouraging efficacy in ALD, he concluded.
—Erik Greb
Suggested Reading
Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630-1638.
Engelen M. Optimizing treatment for cerebral adrenoleukodystrophy in the era of gene therapy. N Engl J Med. 2017;377(17):1682-1684.
KANSAS CITY, MO—Lentiviral gene therapy halts inflammation and demyelination in patients with cerebral adrenoleukodystrophy (ALD), according to research presented at the 46th Annual Meeting of the Child Neurology Society and published in the New England Journal of Medicine. The treatment appears to stabilize neurologic function and to have an acceptable safety profile.
ALD is an X-linked genetic disease caused by a defect in ABCD1, which encodes the peroxisomal ABC half-transporter ALD protein. The defect results in abnormal breakdown of very-long-chain fatty acids, which build up and affect tissues in the nervous system. The most common phenotype of ALD is adrenomyeloneuropathy, which involves axonal degeneration in the spinal cord. A more severe phenotype is childhood cerebral adenopathy, which manifests as an inflammatory demyelination in the white matter.
Allogeneic bone marrow transplantation is the only other treatment with proven efficacy in childhood cerebral ALD. It halts disease progression and improves survival in presymptomatic patients. Finding a donor with identical human leukocyte antigen often is difficult, however. In addition, the treatment entails risks of graft failure and graft-versus-host disease, and the rate of treatment-related mortality is greater than 10%. Gene therapy “may be an alternative to allogeneic bone marrow transplantation, particularly for patients who do not have a matched sibling donor who are at risk for graft failure and graft-versus-host [disease],” said Florian Eichler, MD, Director of the Leukodystrophy Service at Massachusetts General Hospital for Children in Boston.
Researchers Transduced Stem Cells Ex Vivo
In the first trial of its kind, Dr. Eichler and colleagues investigated the safety and efficacy of gene therapy with autologous hematopoietic stem cells for cerebral ALD. The enrollment criteria for the phase II–III, single-arm, open-label study were identical to those for conventional bone marrow transplantation, said Dr. Eichler. Eligible participants were age 17 or younger, had a defect in ABCD1, and had evidence of an active, inflammatory lesion on brain MRI. Children with sibling donors for bone marrow transplantation were excluded from the study.
The investigators obtained CD34+ cells from participants through apheresis and transduced them ex vivo with a lentiviral vector containing normal ABCD1. After undergoing conditioning with busulfan and cyclophosphamide, the patients received an infusion of the transduced CD34+ cells. Patients were assessed regularly for graft-versus-host disease, death, and major functional disabilities. Dr. Eichler and colleagues also monitored participants for changes in neurologic function and increases in MRI lesions. At the end of a two-year follow-up period, patients were offered enrollment in a 13-year long-term follow-up study. The main study’s primary end point was being alive and having no major functional disability at 24 months.
Lesion Progression Stabilized in Most Patients
Dr. Eichler and colleagues treated 17 patients with a mean age at enrollment of 6. Participants’ median Loes score at baseline was 2.0, which indicated a low level of neurologic progression. All patients had an ALD neurologic function scale score of 0 at baseline, indicating an absence of clinical signs of cerebral disease.
The vector copy number in peripheral blood ranged from 0.10 to 1.55 in the 14 patients assessed at month 24. At month 36, the number ranged from 0.36 to 1.83 in the three patients assessed. The number had generally stabilized by two months after infusion. The investigators did not observe preferential integration in or near genes that have previously been associated with serious adverse events related to gene therapy (eg, MDS1, EVI1, and LMO2). All participants had expression of ALD protein in peripheral-blood leukocytes at the most recent follow-up (median follow-up time was 29.4 months). The median percentage of CD14+ cells that expressed ALD protein was 19% at 24 months.
Of the 17 patients, 15 were alive at 24 months and maintained an ALD neurologic function scale score of 0 or 1. In untreated patients, ALD neurologic function scale score usually increases significantly after the first symptoms appear. One patient in the study was progressing rapidly at the time of enrollment and subsequently died of disease progression. Another patient with disease progression on MRI withdrew from the study after the infusion and subsequently died from the complications of an allogeneic transplantation
An exploratory analysis indicated that participants with higher vector copy number in their peripheral blood tended to have better neurologic outcomes, while participants with lower vector copy number tended to have poor neurologic outcomes.
Lesion progression, as measured with the Loes score, had stabilized in 12 of the 17 patients (71%) at the time of the interim analysis. “Half the patients stabilized immediately in their Loes scores after treatment. The other half tended to progress within the first 12 months and then stabilize over time,” said Dr. Eichler.
Gadolinium enhancement resolved in 16 of 17 patients by six months. It reappeared in some patients after treatment, although it was much fainter and more poorly circumscribed, compared with the time of screening, said Dr. Eichler.
The investigators did not observe graft failure or graft-versus-host disease in the population. Most adverse events associated with the treatment were consistent with those associated with myeloablative chemotherapy and occurred during conditioning or during the first two weeks after the infusion. One serious adverse event that possibly was related to treatment was hemorrhagic cystitis associated with BK virus, which resolved with conservative measures.
The results have implications for leukodystrophies in general, according to Dr. Eichler. “Specific phenotypes, even within the same individual leukodystrophy, require different approaches” such as ex vivo or in vivo gene therapy, he added. Overall, the safety data are reassuring, and gene therapy appears to have encouraging efficacy in ALD, he concluded.
—Erik Greb
Suggested Reading
Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630-1638.
Engelen M. Optimizing treatment for cerebral adrenoleukodystrophy in the era of gene therapy. N Engl J Med. 2017;377(17):1682-1684.
Developmental disabilities up significantly since 2014
In 2016, the prevalence of any diagnosed developmental disability in children aged 3-17 years was 6.99% – a statistically significant increase of 21% over the 5.76% recorded in 2014, the NCHS said in a recent Data Brief.
Autism spectrum disorder was up by a similar amount: 23% from 2014, when prevalence was 2.24%, to 2016, when the prevalence was 2.76% among children aged 3-17 years. Intellectual disability rose in 2015 but dropped in 2016, so the overall increase in prevalence was just 3.6%. The prevalence of other developmental delays, on the other hand, held steady from 2014 to 2015 and then took a big jump, 27.5%, in 2016, the NCHS investigators reported.
The estimates are based on reports by parents or guardians of ever receiving a diagnosis of each developmental disability from a physician or other medical professional.
In 2016, the prevalence of any diagnosed developmental disability in children aged 3-17 years was 6.99% – a statistically significant increase of 21% over the 5.76% recorded in 2014, the NCHS said in a recent Data Brief.
Autism spectrum disorder was up by a similar amount: 23% from 2014, when prevalence was 2.24%, to 2016, when the prevalence was 2.76% among children aged 3-17 years. Intellectual disability rose in 2015 but dropped in 2016, so the overall increase in prevalence was just 3.6%. The prevalence of other developmental delays, on the other hand, held steady from 2014 to 2015 and then took a big jump, 27.5%, in 2016, the NCHS investigators reported.
The estimates are based on reports by parents or guardians of ever receiving a diagnosis of each developmental disability from a physician or other medical professional.
In 2016, the prevalence of any diagnosed developmental disability in children aged 3-17 years was 6.99% – a statistically significant increase of 21% over the 5.76% recorded in 2014, the NCHS said in a recent Data Brief.
Autism spectrum disorder was up by a similar amount: 23% from 2014, when prevalence was 2.24%, to 2016, when the prevalence was 2.76% among children aged 3-17 years. Intellectual disability rose in 2015 but dropped in 2016, so the overall increase in prevalence was just 3.6%. The prevalence of other developmental delays, on the other hand, held steady from 2014 to 2015 and then took a big jump, 27.5%, in 2016, the NCHS investigators reported.
The estimates are based on reports by parents or guardians of ever receiving a diagnosis of each developmental disability from a physician or other medical professional.
Vaccine exemptions more common in western states
For the 2016-2017 school year, 2% of American kindergarten students had an exemption from one or more vaccines, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta.
Among the 46 states – including the District of Columbia – that reported data, nine times as many exemptions were granted on religious or philosophical grounds (1.8%) as were granted for medical reasons (0.2%), they said.
Alaska had the highest rate of medical exemptions at 1.5% and Oregon had the highest rate of religious/philosophical exemptions at 6.5%. Thirty states do not allow philosophical exemptions, Arizona and Mississippi do not allow religious exemptions, and West Virginia does not allow either, they noted.
Exemption data were reported for 3,666,870 kindergartners for the 2016-2017 school year and collected by federally funded immunization programs in the 50 states and D.C.
For the 2016-2017 school year, 2% of American kindergarten students had an exemption from one or more vaccines, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta.
Among the 46 states – including the District of Columbia – that reported data, nine times as many exemptions were granted on religious or philosophical grounds (1.8%) as were granted for medical reasons (0.2%), they said.
Alaska had the highest rate of medical exemptions at 1.5% and Oregon had the highest rate of religious/philosophical exemptions at 6.5%. Thirty states do not allow philosophical exemptions, Arizona and Mississippi do not allow religious exemptions, and West Virginia does not allow either, they noted.
Exemption data were reported for 3,666,870 kindergartners for the 2016-2017 school year and collected by federally funded immunization programs in the 50 states and D.C.
For the 2016-2017 school year, 2% of American kindergarten students had an exemption from one or more vaccines, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta.
Among the 46 states – including the District of Columbia – that reported data, nine times as many exemptions were granted on religious or philosophical grounds (1.8%) as were granted for medical reasons (0.2%), they said.
Alaska had the highest rate of medical exemptions at 1.5% and Oregon had the highest rate of religious/philosophical exemptions at 6.5%. Thirty states do not allow philosophical exemptions, Arizona and Mississippi do not allow religious exemptions, and West Virginia does not allow either, they noted.
Exemption data were reported for 3,666,870 kindergartners for the 2016-2017 school year and collected by federally funded immunization programs in the 50 states and D.C.
FROM MMWR
National Academy of Medicine should revisit issue of fetal alcohol exposure
More than 20 years ago the Institute of Medicine (recently renamed the National Academy of Medicine, or NAM) issued its landmark report on fetal alcohol syndrome. Since then, there has been an explosion of research on the issue of fetal alcohol exposure – and NAM needs to revisit the issue and release another report.
Unfortunately, too few physicians and not enough people in the larger society understand public health and that the health status of the unfortunate among us affects the health status of the most fortunate of us. In short, low-income people are the proverbial “canary in the coal mine.”
Accordingly, solving the health care problems of low-income people would solve the health care problems of the middle and upper class. Consider where the United States would be had we paid attention to the opioid epidemic in low-income communities instead of waiting until it spread into everyone’s “safe” communities. We would have tried and tested solutions to the problem as it currently exists.
Another reason NAM needs to revisit FASD – currently proposed to be called neurobehavioral disorders associated with prenatal alcohol exposure in the DSM-5 – are the new findings that link FASD to seizure disorders and other neurodevelopmental disorders of childhood, such as intellectual disability, attention-deficit/hyperactivity disorder, speech and language disorders, motor disorders, specific learning disorders, and autism. In fact, new research is emerging from Robert Freedman, MD, and his team at the University of Colorado Denver, to suggest that preventing choline deficiency in pregnancy (the mechanism producing neurodevelopmental defects in FASD) may not only prevent neurodevelopmental disorders of childhood but also schizophrenia. Further, it has become abundantly clear that choline deficiency (often generated by FASD), is responsible for affect dysregulation, which is a common thread in various forms of violence and suicide.
A recent report highlighted the findings that inmates incarcerated in Mexican prisons have high rates of intellectual disability, and we know that FASD is one of the leading causes of this problem, but we are not screening for it in our juvenile detention centers, jails, or prisons. Consequently, we need to look for the prevalence of FASD in special education as well as in foster care, because these services often feed our correctional institutions. There also is some recent animal evidence suggesting that sufficient prenatal choline during pregnancy may be protective against Alzheimer’s disease – soon to be an even greater public problem in the United States. Lastly, the neuroscience findings regarding FASD also are emerging.
Hence, there is substantial information growing in various, different but overlapping areas of our systems addressing the nation’s public health and well-being. One of the most respected sources of credible science in America is the National Academy Science. The NAM should convene a meeting of the experts to examine the current state of FASD knowledge. If there is sufficient new information, the NAM needs to develop a new report on FASD. It has been 21 years since the first FAS report from the Institute of Medicine and it needs to be revisited. But it appears that the correctional, child protective services, special education, and mental health fields are not aware of the breadth of available research and its importance to the nation’s public health. Determining how fetal alcohol exposure/choline deficiency affects children and adults in special education, foster care, juvenile and adult corrections systems – along with such other social issues as prematurity, disability, unemployment, homelessness, suicide, violence, and mental health – is critical to our nation’s future.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.
More than 20 years ago the Institute of Medicine (recently renamed the National Academy of Medicine, or NAM) issued its landmark report on fetal alcohol syndrome. Since then, there has been an explosion of research on the issue of fetal alcohol exposure – and NAM needs to revisit the issue and release another report.
Unfortunately, too few physicians and not enough people in the larger society understand public health and that the health status of the unfortunate among us affects the health status of the most fortunate of us. In short, low-income people are the proverbial “canary in the coal mine.”
Accordingly, solving the health care problems of low-income people would solve the health care problems of the middle and upper class. Consider where the United States would be had we paid attention to the opioid epidemic in low-income communities instead of waiting until it spread into everyone’s “safe” communities. We would have tried and tested solutions to the problem as it currently exists.
Another reason NAM needs to revisit FASD – currently proposed to be called neurobehavioral disorders associated with prenatal alcohol exposure in the DSM-5 – are the new findings that link FASD to seizure disorders and other neurodevelopmental disorders of childhood, such as intellectual disability, attention-deficit/hyperactivity disorder, speech and language disorders, motor disorders, specific learning disorders, and autism. In fact, new research is emerging from Robert Freedman, MD, and his team at the University of Colorado Denver, to suggest that preventing choline deficiency in pregnancy (the mechanism producing neurodevelopmental defects in FASD) may not only prevent neurodevelopmental disorders of childhood but also schizophrenia. Further, it has become abundantly clear that choline deficiency (often generated by FASD), is responsible for affect dysregulation, which is a common thread in various forms of violence and suicide.
A recent report highlighted the findings that inmates incarcerated in Mexican prisons have high rates of intellectual disability, and we know that FASD is one of the leading causes of this problem, but we are not screening for it in our juvenile detention centers, jails, or prisons. Consequently, we need to look for the prevalence of FASD in special education as well as in foster care, because these services often feed our correctional institutions. There also is some recent animal evidence suggesting that sufficient prenatal choline during pregnancy may be protective against Alzheimer’s disease – soon to be an even greater public problem in the United States. Lastly, the neuroscience findings regarding FASD also are emerging.
Hence, there is substantial information growing in various, different but overlapping areas of our systems addressing the nation’s public health and well-being. One of the most respected sources of credible science in America is the National Academy Science. The NAM should convene a meeting of the experts to examine the current state of FASD knowledge. If there is sufficient new information, the NAM needs to develop a new report on FASD. It has been 21 years since the first FAS report from the Institute of Medicine and it needs to be revisited. But it appears that the correctional, child protective services, special education, and mental health fields are not aware of the breadth of available research and its importance to the nation’s public health. Determining how fetal alcohol exposure/choline deficiency affects children and adults in special education, foster care, juvenile and adult corrections systems – along with such other social issues as prematurity, disability, unemployment, homelessness, suicide, violence, and mental health – is critical to our nation’s future.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.
More than 20 years ago the Institute of Medicine (recently renamed the National Academy of Medicine, or NAM) issued its landmark report on fetal alcohol syndrome. Since then, there has been an explosion of research on the issue of fetal alcohol exposure – and NAM needs to revisit the issue and release another report.
Unfortunately, too few physicians and not enough people in the larger society understand public health and that the health status of the unfortunate among us affects the health status of the most fortunate of us. In short, low-income people are the proverbial “canary in the coal mine.”
Accordingly, solving the health care problems of low-income people would solve the health care problems of the middle and upper class. Consider where the United States would be had we paid attention to the opioid epidemic in low-income communities instead of waiting until it spread into everyone’s “safe” communities. We would have tried and tested solutions to the problem as it currently exists.
Another reason NAM needs to revisit FASD – currently proposed to be called neurobehavioral disorders associated with prenatal alcohol exposure in the DSM-5 – are the new findings that link FASD to seizure disorders and other neurodevelopmental disorders of childhood, such as intellectual disability, attention-deficit/hyperactivity disorder, speech and language disorders, motor disorders, specific learning disorders, and autism. In fact, new research is emerging from Robert Freedman, MD, and his team at the University of Colorado Denver, to suggest that preventing choline deficiency in pregnancy (the mechanism producing neurodevelopmental defects in FASD) may not only prevent neurodevelopmental disorders of childhood but also schizophrenia. Further, it has become abundantly clear that choline deficiency (often generated by FASD), is responsible for affect dysregulation, which is a common thread in various forms of violence and suicide.
A recent report highlighted the findings that inmates incarcerated in Mexican prisons have high rates of intellectual disability, and we know that FASD is one of the leading causes of this problem, but we are not screening for it in our juvenile detention centers, jails, or prisons. Consequently, we need to look for the prevalence of FASD in special education as well as in foster care, because these services often feed our correctional institutions. There also is some recent animal evidence suggesting that sufficient prenatal choline during pregnancy may be protective against Alzheimer’s disease – soon to be an even greater public problem in the United States. Lastly, the neuroscience findings regarding FASD also are emerging.
Hence, there is substantial information growing in various, different but overlapping areas of our systems addressing the nation’s public health and well-being. One of the most respected sources of credible science in America is the National Academy Science. The NAM should convene a meeting of the experts to examine the current state of FASD knowledge. If there is sufficient new information, the NAM needs to develop a new report on FASD. It has been 21 years since the first FAS report from the Institute of Medicine and it needs to be revisited. But it appears that the correctional, child protective services, special education, and mental health fields are not aware of the breadth of available research and its importance to the nation’s public health. Determining how fetal alcohol exposure/choline deficiency affects children and adults in special education, foster care, juvenile and adult corrections systems – along with such other social issues as prematurity, disability, unemployment, homelessness, suicide, violence, and mental health – is critical to our nation’s future.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.
Hawaii experiencing a statewide outbreak of mumps
As of Nov. 30, 2017, 636 cases of mumps had been confirmed in Hawaii, according to the state’s Department of Health (DOH).
The Hawaii DOH originally reported 14 confirmed mumps cases statewide in April 2017, but the number of confirmed cases has increased by more than 4,000% since that time.
In the midst of the outbreak, the Hawaii DOH recommends that all adolescents between the aged 10-19 years old, and adults born in or after 1957, should receive an additional MMR vaccine dose as soon as possible. The outbreak dose is recommended regardless of previous vaccination or documented immunity to mumps. Administering additional doses of vaccine is not an ideal situation, the DOH noted, but said it should not cause any medical complications.
The Hawaii DOH will investigate mumps cases statewide as the outbreak continues.
As of Nov. 30, 2017, 636 cases of mumps had been confirmed in Hawaii, according to the state’s Department of Health (DOH).
The Hawaii DOH originally reported 14 confirmed mumps cases statewide in April 2017, but the number of confirmed cases has increased by more than 4,000% since that time.
In the midst of the outbreak, the Hawaii DOH recommends that all adolescents between the aged 10-19 years old, and adults born in or after 1957, should receive an additional MMR vaccine dose as soon as possible. The outbreak dose is recommended regardless of previous vaccination or documented immunity to mumps. Administering additional doses of vaccine is not an ideal situation, the DOH noted, but said it should not cause any medical complications.
The Hawaii DOH will investigate mumps cases statewide as the outbreak continues.
As of Nov. 30, 2017, 636 cases of mumps had been confirmed in Hawaii, according to the state’s Department of Health (DOH).
The Hawaii DOH originally reported 14 confirmed mumps cases statewide in April 2017, but the number of confirmed cases has increased by more than 4,000% since that time.
In the midst of the outbreak, the Hawaii DOH recommends that all adolescents between the aged 10-19 years old, and adults born in or after 1957, should receive an additional MMR vaccine dose as soon as possible. The outbreak dose is recommended regardless of previous vaccination or documented immunity to mumps. Administering additional doses of vaccine is not an ideal situation, the DOH noted, but said it should not cause any medical complications.
The Hawaii DOH will investigate mumps cases statewide as the outbreak continues.
Attack on asthma: Scrubbing homes of allergens may tame disease and its costs
After years of studying the causes of asthma, a pediatrician-turned-public health sleuth thinks there’s a way to substantially reduce its impact.
But the approach faces a big hurdle: getting someone to pay for it, said Elizabeth C. Matsui, MD, a professor at Johns Hopkins University in Baltimore.
Dr. Matsui, who suffered from asthma as a child, has spent much of her career studying the link between poor housing and asthma in low-income neighborhoods. In particular, she’s looked at the effects of mouse allergens, typically found in high concentrations in urban homes.
Dr. Matsui cited a 2004 study in the New England Journal of Medicine that described measures to reduce home allergen levels and concluded that they were linked to reductions in asthma symptoms.
That research “was highly successful and impactful,” but the approach wasn’t widely adopted, according to Dr. Matsui.
“So here we have this trial that was published more than 10 years ago that shows [indoor allergen control] works,” said Dr. Matsui, who did not participate in the study. “But the families who need it most can’t afford to do these things, don’t have control oftentimes over their home environment, and insurance or other payers don’t cover these things.”
Dr. Matsui has proposed new incentives for hospitals to provide home intervention, including Medicaid waivers. But, she said, scientists can’t use research money for these programs. “Delivery of community health care programs would require a different type of funding.”
As a result, doctors and scientists doubted if a plan to control home allergens would scale up, and insurers questioned whether benefits to their bottom line would justify the added cost.
“We have this enormous public health problem in that there are housing conditions that directly affect allergen exposure in this population of kids,” Dr. Matsui said. “We have dedicated individuals and groups who are trying to solve the problem. But we don’t have a system that is able to solve the problem.”
A 2017 study by Dr. Matsui, published in JAMA, suggests that even without intensive professional cleaning services, families that receive some training can substantially reduce home allergens on their own.
That finding suggests health agencies should routinely offer to educate asthma-affected families in home allergen control. “There’s potentially a large benefit,” Dr. Matsui said.
In a separate study, Dr. Matsui’s group is following 200 Baltimore children to see if those in homes scrubbed of allergens need fewer treatments with rescue inhalers. If they do, that could give health insurers an incentive to pay for the approach.
There’s another incentive: Clearing the air in a child’s home may be critical in cases where medications alone don’t work. “We continue to see a lot of kids that, despite being on medication, don’t have well-controlled asthma,” Dr. Matsui said.
Asthma drugs can also have serious side effects, she said, especially at higher doses, and may suppress symptoms without halting lung damage.
Dr. Matsui’s work on asthma began while working as a pediatrician at Baltimore’s Franklin Square Hospital in 1998. As part of her job, she spent a half-day each week in a school health clinic in a low-income area.
Dr. Matsui was struck by the number of kids she saw with severe asthma, she said, and set up a home health visit program to help them. But she wasn’t certain the program was working, so she consulted with experts at Hopkins.
In 2004, she earned a master’s from the Johns Hopkins School of Public Health. Today, she is one of the nation’s leading asthma researchers.
Dr. Matsui said her career was shaped by her own struggle with childhood asthma. “I think that that probably played a role, consciously or unconsciously,” she said.
KHN’s coverage of health disparities in east Baltimore is supported by The Annie E. Casey Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Environment is certainly a factor in asthma control. We are lucky enough to have a network in our county that will take pediatric asthma cases to help with asthma education. The nurse will even accompany the child and parent to their outpatient visits to help advocate for help with their asthma management and go into the home to see if there is a cockroach problem or a dusty environment, for example. They will also help families learn how to better organize the child’s bedroom so there is less dust! Some Medicaid HMOs will pay for this care management plan but not all of the insurances in our area.
Environment is certainly a factor in asthma control. We are lucky enough to have a network in our county that will take pediatric asthma cases to help with asthma education. The nurse will even accompany the child and parent to their outpatient visits to help advocate for help with their asthma management and go into the home to see if there is a cockroach problem or a dusty environment, for example. They will also help families learn how to better organize the child’s bedroom so there is less dust! Some Medicaid HMOs will pay for this care management plan but not all of the insurances in our area.
Environment is certainly a factor in asthma control. We are lucky enough to have a network in our county that will take pediatric asthma cases to help with asthma education. The nurse will even accompany the child and parent to their outpatient visits to help advocate for help with their asthma management and go into the home to see if there is a cockroach problem or a dusty environment, for example. They will also help families learn how to better organize the child’s bedroom so there is less dust! Some Medicaid HMOs will pay for this care management plan but not all of the insurances in our area.
After years of studying the causes of asthma, a pediatrician-turned-public health sleuth thinks there’s a way to substantially reduce its impact.
But the approach faces a big hurdle: getting someone to pay for it, said Elizabeth C. Matsui, MD, a professor at Johns Hopkins University in Baltimore.
Dr. Matsui, who suffered from asthma as a child, has spent much of her career studying the link between poor housing and asthma in low-income neighborhoods. In particular, she’s looked at the effects of mouse allergens, typically found in high concentrations in urban homes.
Dr. Matsui cited a 2004 study in the New England Journal of Medicine that described measures to reduce home allergen levels and concluded that they were linked to reductions in asthma symptoms.
That research “was highly successful and impactful,” but the approach wasn’t widely adopted, according to Dr. Matsui.
“So here we have this trial that was published more than 10 years ago that shows [indoor allergen control] works,” said Dr. Matsui, who did not participate in the study. “But the families who need it most can’t afford to do these things, don’t have control oftentimes over their home environment, and insurance or other payers don’t cover these things.”
Dr. Matsui has proposed new incentives for hospitals to provide home intervention, including Medicaid waivers. But, she said, scientists can’t use research money for these programs. “Delivery of community health care programs would require a different type of funding.”
As a result, doctors and scientists doubted if a plan to control home allergens would scale up, and insurers questioned whether benefits to their bottom line would justify the added cost.
“We have this enormous public health problem in that there are housing conditions that directly affect allergen exposure in this population of kids,” Dr. Matsui said. “We have dedicated individuals and groups who are trying to solve the problem. But we don’t have a system that is able to solve the problem.”
A 2017 study by Dr. Matsui, published in JAMA, suggests that even without intensive professional cleaning services, families that receive some training can substantially reduce home allergens on their own.
That finding suggests health agencies should routinely offer to educate asthma-affected families in home allergen control. “There’s potentially a large benefit,” Dr. Matsui said.
In a separate study, Dr. Matsui’s group is following 200 Baltimore children to see if those in homes scrubbed of allergens need fewer treatments with rescue inhalers. If they do, that could give health insurers an incentive to pay for the approach.
There’s another incentive: Clearing the air in a child’s home may be critical in cases where medications alone don’t work. “We continue to see a lot of kids that, despite being on medication, don’t have well-controlled asthma,” Dr. Matsui said.
Asthma drugs can also have serious side effects, she said, especially at higher doses, and may suppress symptoms without halting lung damage.
Dr. Matsui’s work on asthma began while working as a pediatrician at Baltimore’s Franklin Square Hospital in 1998. As part of her job, she spent a half-day each week in a school health clinic in a low-income area.
Dr. Matsui was struck by the number of kids she saw with severe asthma, she said, and set up a home health visit program to help them. But she wasn’t certain the program was working, so she consulted with experts at Hopkins.
In 2004, she earned a master’s from the Johns Hopkins School of Public Health. Today, she is one of the nation’s leading asthma researchers.
Dr. Matsui said her career was shaped by her own struggle with childhood asthma. “I think that that probably played a role, consciously or unconsciously,” she said.
KHN’s coverage of health disparities in east Baltimore is supported by The Annie E. Casey Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
After years of studying the causes of asthma, a pediatrician-turned-public health sleuth thinks there’s a way to substantially reduce its impact.
But the approach faces a big hurdle: getting someone to pay for it, said Elizabeth C. Matsui, MD, a professor at Johns Hopkins University in Baltimore.
Dr. Matsui, who suffered from asthma as a child, has spent much of her career studying the link between poor housing and asthma in low-income neighborhoods. In particular, she’s looked at the effects of mouse allergens, typically found in high concentrations in urban homes.
Dr. Matsui cited a 2004 study in the New England Journal of Medicine that described measures to reduce home allergen levels and concluded that they were linked to reductions in asthma symptoms.
That research “was highly successful and impactful,” but the approach wasn’t widely adopted, according to Dr. Matsui.
“So here we have this trial that was published more than 10 years ago that shows [indoor allergen control] works,” said Dr. Matsui, who did not participate in the study. “But the families who need it most can’t afford to do these things, don’t have control oftentimes over their home environment, and insurance or other payers don’t cover these things.”
Dr. Matsui has proposed new incentives for hospitals to provide home intervention, including Medicaid waivers. But, she said, scientists can’t use research money for these programs. “Delivery of community health care programs would require a different type of funding.”
As a result, doctors and scientists doubted if a plan to control home allergens would scale up, and insurers questioned whether benefits to their bottom line would justify the added cost.
“We have this enormous public health problem in that there are housing conditions that directly affect allergen exposure in this population of kids,” Dr. Matsui said. “We have dedicated individuals and groups who are trying to solve the problem. But we don’t have a system that is able to solve the problem.”
A 2017 study by Dr. Matsui, published in JAMA, suggests that even without intensive professional cleaning services, families that receive some training can substantially reduce home allergens on their own.
That finding suggests health agencies should routinely offer to educate asthma-affected families in home allergen control. “There’s potentially a large benefit,” Dr. Matsui said.
In a separate study, Dr. Matsui’s group is following 200 Baltimore children to see if those in homes scrubbed of allergens need fewer treatments with rescue inhalers. If they do, that could give health insurers an incentive to pay for the approach.
There’s another incentive: Clearing the air in a child’s home may be critical in cases where medications alone don’t work. “We continue to see a lot of kids that, despite being on medication, don’t have well-controlled asthma,” Dr. Matsui said.
Asthma drugs can also have serious side effects, she said, especially at higher doses, and may suppress symptoms without halting lung damage.
Dr. Matsui’s work on asthma began while working as a pediatrician at Baltimore’s Franklin Square Hospital in 1998. As part of her job, she spent a half-day each week in a school health clinic in a low-income area.
Dr. Matsui was struck by the number of kids she saw with severe asthma, she said, and set up a home health visit program to help them. But she wasn’t certain the program was working, so she consulted with experts at Hopkins.
In 2004, she earned a master’s from the Johns Hopkins School of Public Health. Today, she is one of the nation’s leading asthma researchers.
Dr. Matsui said her career was shaped by her own struggle with childhood asthma. “I think that that probably played a role, consciously or unconsciously,” she said.
KHN’s coverage of health disparities in east Baltimore is supported by The Annie E. Casey Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
More states allowing pharmacists to administer vaccines to younger patients
.
Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.
Yet barriers to pharmacists’ providing immunization services remain because of some state laws. Laws in nine states that prevent pharmacists from vaccinating patients younger than age 18 years keep pharmacists from administering any of the vaccines listed in the 2016 Advisory Committee of Immunization Practices child immunization schedule. The two states in which pharmacists can vaccinate patients as young as 14 years allow the pharmacists to administer only the recommended booster for meningococcal vaccine and annual influenza vaccines for children. And the 15 states with minimum patient age restrictions for 7- to 12-year-oldss allow pharmacists to administer only the four vaccines ACIP recommends on the 2016 schedule for children (meningococcal, Tdap, human papillomavirus, and annual influenza vaccines).
Read more in the Journal of the American Pharmacists Association (2017 Nov-Dec;57[6]:661-9).
.
Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.
Yet barriers to pharmacists’ providing immunization services remain because of some state laws. Laws in nine states that prevent pharmacists from vaccinating patients younger than age 18 years keep pharmacists from administering any of the vaccines listed in the 2016 Advisory Committee of Immunization Practices child immunization schedule. The two states in which pharmacists can vaccinate patients as young as 14 years allow the pharmacists to administer only the recommended booster for meningococcal vaccine and annual influenza vaccines for children. And the 15 states with minimum patient age restrictions for 7- to 12-year-oldss allow pharmacists to administer only the four vaccines ACIP recommends on the 2016 schedule for children (meningococcal, Tdap, human papillomavirus, and annual influenza vaccines).
Read more in the Journal of the American Pharmacists Association (2017 Nov-Dec;57[6]:661-9).
.
Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.
Yet barriers to pharmacists’ providing immunization services remain because of some state laws. Laws in nine states that prevent pharmacists from vaccinating patients younger than age 18 years keep pharmacists from administering any of the vaccines listed in the 2016 Advisory Committee of Immunization Practices child immunization schedule. The two states in which pharmacists can vaccinate patients as young as 14 years allow the pharmacists to administer only the recommended booster for meningococcal vaccine and annual influenza vaccines for children. And the 15 states with minimum patient age restrictions for 7- to 12-year-oldss allow pharmacists to administer only the four vaccines ACIP recommends on the 2016 schedule for children (meningococcal, Tdap, human papillomavirus, and annual influenza vaccines).
Read more in the Journal of the American Pharmacists Association (2017 Nov-Dec;57[6]:661-9).
FROM THE JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
Parents taking photos of kids’ lesions for telederm diagnosis looks promising
, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.
Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.
Concordance between photograph-based vs. in-person diagnosis was 83%. In three cases, diagnoses could not be made by the remote dermatologist because of poor photograph quality. When those cases were excluded, concordance was 89% between photograph-based vs. in-person diagnosis. Concordance for birthmarks was 100%, 92% for rashes, and 64% for alopecia-related diagnoses. Of four cases that were misdiagnosed, there were three cases of alopecia and one nodule.
Half the parents received a simple, three-step instruction sheet on smartphone photography. There was no statistical difference in diagnostic concordance between the parents who received the instruction sheet and those who didn’t.
“When dealing with categories with low concordance, such as alopecia and nodules and tumors, teledermatology practitioners may need to be cautious about attempting definitive diagnoses in some cases, and may need to refer patients for in-person consultation,” Dr. O’Connor and his associates wrote. “For these cases, teledermatology may still serve as a triage tool. For example, patients with suspicious nodules could be referred for expedited appointments in specialty clinics, whereas patients with isolated alopecia could be scheduled for routine visits. Conversely, in diagnostic categories with high concordance, such as birthmarks and rashes, certain cases could be definitively diagnosed and treated exclusively using teledermatology (for example, mild acne).”
Read more in JAMA Dermatology (2017 Nov 15. doi: 10.1001/jamadermatol.2017.4280).
, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.
Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.
Concordance between photograph-based vs. in-person diagnosis was 83%. In three cases, diagnoses could not be made by the remote dermatologist because of poor photograph quality. When those cases were excluded, concordance was 89% between photograph-based vs. in-person diagnosis. Concordance for birthmarks was 100%, 92% for rashes, and 64% for alopecia-related diagnoses. Of four cases that were misdiagnosed, there were three cases of alopecia and one nodule.
Half the parents received a simple, three-step instruction sheet on smartphone photography. There was no statistical difference in diagnostic concordance between the parents who received the instruction sheet and those who didn’t.
“When dealing with categories with low concordance, such as alopecia and nodules and tumors, teledermatology practitioners may need to be cautious about attempting definitive diagnoses in some cases, and may need to refer patients for in-person consultation,” Dr. O’Connor and his associates wrote. “For these cases, teledermatology may still serve as a triage tool. For example, patients with suspicious nodules could be referred for expedited appointments in specialty clinics, whereas patients with isolated alopecia could be scheduled for routine visits. Conversely, in diagnostic categories with high concordance, such as birthmarks and rashes, certain cases could be definitively diagnosed and treated exclusively using teledermatology (for example, mild acne).”
Read more in JAMA Dermatology (2017 Nov 15. doi: 10.1001/jamadermatol.2017.4280).
, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.
Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.
Concordance between photograph-based vs. in-person diagnosis was 83%. In three cases, diagnoses could not be made by the remote dermatologist because of poor photograph quality. When those cases were excluded, concordance was 89% between photograph-based vs. in-person diagnosis. Concordance for birthmarks was 100%, 92% for rashes, and 64% for alopecia-related diagnoses. Of four cases that were misdiagnosed, there were three cases of alopecia and one nodule.
Half the parents received a simple, three-step instruction sheet on smartphone photography. There was no statistical difference in diagnostic concordance between the parents who received the instruction sheet and those who didn’t.
“When dealing with categories with low concordance, such as alopecia and nodules and tumors, teledermatology practitioners may need to be cautious about attempting definitive diagnoses in some cases, and may need to refer patients for in-person consultation,” Dr. O’Connor and his associates wrote. “For these cases, teledermatology may still serve as a triage tool. For example, patients with suspicious nodules could be referred for expedited appointments in specialty clinics, whereas patients with isolated alopecia could be scheduled for routine visits. Conversely, in diagnostic categories with high concordance, such as birthmarks and rashes, certain cases could be definitively diagnosed and treated exclusively using teledermatology (for example, mild acne).”
Read more in JAMA Dermatology (2017 Nov 15. doi: 10.1001/jamadermatol.2017.4280).
FROM JAMA DERMATOLOGY