Micrograph showing BCP-ALL

Image by Vashi Donsk

Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.

Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.

And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.

“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.

“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”

For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.

According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.

Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.

Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).

Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.

The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.

Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).

Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).

The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.

The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes.

Micrograph showing BCP-ALL

Image by Vashi Donsk

Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.

Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.

And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.

“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.

“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”

For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.

According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.

Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.

Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).

Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.

The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.

Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).

Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).

The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.

The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes.

Micrograph showing BCP-ALL

Image by Vashi Donsk

Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.

Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.

And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.

“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.

“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”

For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.

According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.

Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.

Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).

Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.

The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.

Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).

Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).

The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.

The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes.

The State of Hospital Medicine Report (SoHM) is the most comprehensive survey of hospital medicine in the country and provides current data on hospitalist compensation and productivity, plus covers practice demographics, staffing levels, staff growth, and compensation models.

Don’t miss out on getting your copy when it becomes available. Order now at www.hospitalmedicine.org/survey and be notified directly when the report is released.

The State of Hospital Medicine Report (SoHM) is the most comprehensive survey of hospital medicine in the country and provides current data on hospitalist compensation and productivity, plus covers practice demographics, staffing levels, staff growth, and compensation models.

Don’t miss out on getting your copy when it becomes available. Order now at www.hospitalmedicine.org/survey and be notified directly when the report is released.

The State of Hospital Medicine Report (SoHM) is the most comprehensive survey of hospital medicine in the country and provides current data on hospitalist compensation and productivity, plus covers practice demographics, staffing levels, staff growth, and compensation models.

Don’t miss out on getting your copy when it becomes available. Order now at www.hospitalmedicine.org/survey and be notified directly when the report is released.

One of the most important questions for leaders of hospital medicine groups is, “How can I measure the level of engagement of my hospitalists?” Measuring hospitalist engagement can be difficult, and many leaders are not satisfied with the tools they currently have at their disposal.

SHM developed an Engagement Benchmarking Service that evaluates care quality, autonomy, effective motivation, burnout risk, and more. You can see your standardization scores ranked against national benchmarks to help you determine what’s working well and what needs improvement.

Recruiting ends at the end of September, so register now for the next cohort at www.hospitalmedicine.org/pmad3.

One of the most important questions for leaders of hospital medicine groups is, “How can I measure the level of engagement of my hospitalists?” Measuring hospitalist engagement can be difficult, and many leaders are not satisfied with the tools they currently have at their disposal.

SHM developed an Engagement Benchmarking Service that evaluates care quality, autonomy, effective motivation, burnout risk, and more. You can see your standardization scores ranked against national benchmarks to help you determine what’s working well and what needs improvement.

Recruiting ends at the end of September, so register now for the next cohort at www.hospitalmedicine.org/pmad3.

One of the most important questions for leaders of hospital medicine groups is, “How can I measure the level of engagement of my hospitalists?” Measuring hospitalist engagement can be difficult, and many leaders are not satisfied with the tools they currently have at their disposal.

SHM developed an Engagement Benchmarking Service that evaluates care quality, autonomy, effective motivation, burnout risk, and more. You can see your standardization scores ranked against national benchmarks to help you determine what’s working well and what needs improvement.

Recruiting ends at the end of September, so register now for the next cohort at www.hospitalmedicine.org/pmad3.

Platelets for transfusion

Photo from Flickr

Researchers have reported 2 cases in which the Zika virus seems to have been transmitted via platelet transfusion.

Brazilian health officials previously announced 2 cases of Zika virus—in a liver transplant recipient and a gunshot victim—that likely resulted from blood transfusions performed in 2015.

Now, researchers have reported possible transmission via transfusion in 2 more Brazilians—a patient with primary myelofibrosis (PMF) and one with acute myeloid leukemia (AML).

The researchers described these cases in a letter to NEJM.

An individual who donated platelets via apheresis on January 16, 2016, later tested positive for the Zika virus.

On January 19, platelets from that donor were transfused into a 54-year-old woman with PMF and a 14-year-old girl with AML who had also received a haploidentical bone marrow transplant on January 6.

The platelet donor called the blood bank on January 21 to report worrying symptoms—a cutaneous rash, retro-orbital pain, and pain in both knees—that had developed on January 18.

Subsequent testing revealed that the donor was negative for chikungunya and dengue virus. However, both plasma and urine samples tested positive for Zika virus.

Pre-transfusion samples collected from both of the recipients were negative for chikungunya, dengue, and Zika. However, samples collected after the transfusions—6 days after for the woman with PMF and 23 to 51 days after for the girl with AML—tested positive for Zika.

Researchers performed molecular sequencing and phylogenetic analysis of Zika virus RNA isolated from the donor and the recipients. Isolates from all 3 parties had nucleotide changes in the envelope gene (codons 11 and 186) that were not observed among other available isolates from Brazil.

The researchers said these results suggest the platelet transfusions were the source of Zika virus infection in the PMF patient and the AML patient.

Although both patients could have been exposed to Zika-carrying mosquitoes, both the RNA results and the timing of Zika infection suggest the transfusions were the cause.

Platelets for transfusion

Photo from Flickr

Researchers have reported 2 cases in which the Zika virus seems to have been transmitted via platelet transfusion.

Brazilian health officials previously announced 2 cases of Zika virus—in a liver transplant recipient and a gunshot victim—that likely resulted from blood transfusions performed in 2015.

Now, researchers have reported possible transmission via transfusion in 2 more Brazilians—a patient with primary myelofibrosis (PMF) and one with acute myeloid leukemia (AML).

The researchers described these cases in a letter to NEJM.

An individual who donated platelets via apheresis on January 16, 2016, later tested positive for the Zika virus.

On January 19, platelets from that donor were transfused into a 54-year-old woman with PMF and a 14-year-old girl with AML who had also received a haploidentical bone marrow transplant on January 6.

The platelet donor called the blood bank on January 21 to report worrying symptoms—a cutaneous rash, retro-orbital pain, and pain in both knees—that had developed on January 18.

Subsequent testing revealed that the donor was negative for chikungunya and dengue virus. However, both plasma and urine samples tested positive for Zika virus.

Pre-transfusion samples collected from both of the recipients were negative for chikungunya, dengue, and Zika. However, samples collected after the transfusions—6 days after for the woman with PMF and 23 to 51 days after for the girl with AML—tested positive for Zika.

Researchers performed molecular sequencing and phylogenetic analysis of Zika virus RNA isolated from the donor and the recipients. Isolates from all 3 parties had nucleotide changes in the envelope gene (codons 11 and 186) that were not observed among other available isolates from Brazil.

The researchers said these results suggest the platelet transfusions were the source of Zika virus infection in the PMF patient and the AML patient.

Although both patients could have been exposed to Zika-carrying mosquitoes, both the RNA results and the timing of Zika infection suggest the transfusions were the cause.

Platelets for transfusion

Photo from Flickr

Researchers have reported 2 cases in which the Zika virus seems to have been transmitted via platelet transfusion.

Brazilian health officials previously announced 2 cases of Zika virus—in a liver transplant recipient and a gunshot victim—that likely resulted from blood transfusions performed in 2015.

Now, researchers have reported possible transmission via transfusion in 2 more Brazilians—a patient with primary myelofibrosis (PMF) and one with acute myeloid leukemia (AML).

The researchers described these cases in a letter to NEJM.

An individual who donated platelets via apheresis on January 16, 2016, later tested positive for the Zika virus.

On January 19, platelets from that donor were transfused into a 54-year-old woman with PMF and a 14-year-old girl with AML who had also received a haploidentical bone marrow transplant on January 6.

The platelet donor called the blood bank on January 21 to report worrying symptoms—a cutaneous rash, retro-orbital pain, and pain in both knees—that had developed on January 18.

Subsequent testing revealed that the donor was negative for chikungunya and dengue virus. However, both plasma and urine samples tested positive for Zika virus.

Pre-transfusion samples collected from both of the recipients were negative for chikungunya, dengue, and Zika. However, samples collected after the transfusions—6 days after for the woman with PMF and 23 to 51 days after for the girl with AML—tested positive for Zika.

Researchers performed molecular sequencing and phylogenetic analysis of Zika virus RNA isolated from the donor and the recipients. Isolates from all 3 parties had nucleotide changes in the envelope gene (codons 11 and 186) that were not observed among other available isolates from Brazil.

The researchers said these results suggest the platelet transfusions were the source of Zika virus infection in the PMF patient and the AML patient.

Although both patients could have been exposed to Zika-carrying mosquitoes, both the RNA results and the timing of Zika infection suggest the transfusions were the cause.

Pregnant woman

Photo by Nina Matthews

New research suggests expanded prenatal genetic testing may increase the detection of carrier status for potentially serious genetic conditions, including hemoglobinopathies.

Researchers analyzed nearly 350,000 adults of diverse racial and ethnic backgrounds and found evidence to suggest that expanded screening for up to 94 conditions can increase the detection of carrier status when compared with current genetic testing recommendations from professional societies.

Imran S. Haque, PhD, of Counsyl in San Francisco, California, and his colleagues reported these findings in JAMA. The study was funded by Counsyl, a laboratory providing expanded carrier screening.

Genetic testing of prospective parents to detect carriers of specific inherited recessive diseases is part of routine obstetrical practice. The current recommendations are to test for a limited number of individual diseases, in part based on self-reported racial/ethnic background.

Dr Haque and his colleagues wanted to determine if recent advances in genetic testing could facilitate screening for an expanded number of conditions independent of racial/ethnic background.

The researchers analyzed results from expanded carrier screening in 346,790 reproductive-aged individuals, primarily from the US, without known indication for specific genetic testing.

The individuals were tested for carrier status for up to 94 conditions. Tests were offered by clinicians providing reproductive care.

Risk was defined as the probability that a hypothetical fetus created from a random pairing of individuals (within or across 15 self-reported racial/ethnic categories) would be homozygous or compound heterozygous for 2 mutations presumed to cause severe or profound disease.

Severe conditions were defined as those that, if left untreated, cause intellectual disability or a substantially shortened lifespan. Profound conditions were those causing both intellectual disability and a shortened lifespan.

The researchers found that, in most racial/ethnic categories, expanded carrier screening modeled more hypothetical fetuses at risk for severe or profound conditions than did screening based on current professional guidelines.

Overall, relative to expanded carrier screening, guideline-based screening ranged from identifying 6% of hypothetical fetuses affected for East Asian couples to 87% for African or African American couples.

Though this study suggests expanded screening could be beneficial, the researchers said their findings should be confirmed with prospective studies comparing current carrier screening with expanded screening in at-risk populations.

Pregnant woman

Photo by Nina Matthews

New research suggests expanded prenatal genetic testing may increase the detection of carrier status for potentially serious genetic conditions, including hemoglobinopathies.

Researchers analyzed nearly 350,000 adults of diverse racial and ethnic backgrounds and found evidence to suggest that expanded screening for up to 94 conditions can increase the detection of carrier status when compared with current genetic testing recommendations from professional societies.

Imran S. Haque, PhD, of Counsyl in San Francisco, California, and his colleagues reported these findings in JAMA. The study was funded by Counsyl, a laboratory providing expanded carrier screening.

Genetic testing of prospective parents to detect carriers of specific inherited recessive diseases is part of routine obstetrical practice. The current recommendations are to test for a limited number of individual diseases, in part based on self-reported racial/ethnic background.

Dr Haque and his colleagues wanted to determine if recent advances in genetic testing could facilitate screening for an expanded number of conditions independent of racial/ethnic background.

The researchers analyzed results from expanded carrier screening in 346,790 reproductive-aged individuals, primarily from the US, without known indication for specific genetic testing.

The individuals were tested for carrier status for up to 94 conditions. Tests were offered by clinicians providing reproductive care.

Risk was defined as the probability that a hypothetical fetus created from a random pairing of individuals (within or across 15 self-reported racial/ethnic categories) would be homozygous or compound heterozygous for 2 mutations presumed to cause severe or profound disease.

Severe conditions were defined as those that, if left untreated, cause intellectual disability or a substantially shortened lifespan. Profound conditions were those causing both intellectual disability and a shortened lifespan.

The researchers found that, in most racial/ethnic categories, expanded carrier screening modeled more hypothetical fetuses at risk for severe or profound conditions than did screening based on current professional guidelines.

Overall, relative to expanded carrier screening, guideline-based screening ranged from identifying 6% of hypothetical fetuses affected for East Asian couples to 87% for African or African American couples.

Though this study suggests expanded screening could be beneficial, the researchers said their findings should be confirmed with prospective studies comparing current carrier screening with expanded screening in at-risk populations.

Pregnant woman

Photo by Nina Matthews

New research suggests expanded prenatal genetic testing may increase the detection of carrier status for potentially serious genetic conditions, including hemoglobinopathies.

Researchers analyzed nearly 350,000 adults of diverse racial and ethnic backgrounds and found evidence to suggest that expanded screening for up to 94 conditions can increase the detection of carrier status when compared with current genetic testing recommendations from professional societies.

Imran S. Haque, PhD, of Counsyl in San Francisco, California, and his colleagues reported these findings in JAMA. The study was funded by Counsyl, a laboratory providing expanded carrier screening.

Genetic testing of prospective parents to detect carriers of specific inherited recessive diseases is part of routine obstetrical practice. The current recommendations are to test for a limited number of individual diseases, in part based on self-reported racial/ethnic background.

Dr Haque and his colleagues wanted to determine if recent advances in genetic testing could facilitate screening for an expanded number of conditions independent of racial/ethnic background.

The researchers analyzed results from expanded carrier screening in 346,790 reproductive-aged individuals, primarily from the US, without known indication for specific genetic testing.

The individuals were tested for carrier status for up to 94 conditions. Tests were offered by clinicians providing reproductive care.

Risk was defined as the probability that a hypothetical fetus created from a random pairing of individuals (within or across 15 self-reported racial/ethnic categories) would be homozygous or compound heterozygous for 2 mutations presumed to cause severe or profound disease.

Severe conditions were defined as those that, if left untreated, cause intellectual disability or a substantially shortened lifespan. Profound conditions were those causing both intellectual disability and a shortened lifespan.

The researchers found that, in most racial/ethnic categories, expanded carrier screening modeled more hypothetical fetuses at risk for severe or profound conditions than did screening based on current professional guidelines.

Overall, relative to expanded carrier screening, guideline-based screening ranged from identifying 6% of hypothetical fetuses affected for East Asian couples to 87% for African or African American couples.

Though this study suggests expanded screening could be beneficial, the researchers said their findings should be confirmed with prospective studies comparing current carrier screening with expanded screening in at-risk populations.

T cells

Image by NIAID

The European Commission (EC) has granted conditional marketing authorization for an immunogene therapy known as Zalmoxis.

This means Zalmoxis can be marketed in the European Economic Area as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults with high-risk hematologic malignancies who are receiving a haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Zalmoxis consists of allogeneic T cells genetically modified to express both a truncated form of the human low-affinity nerve growth factor receptor (ΔLNGFR), as a cell-surface selectable marker, and the suicide gene herpes simplex I virus thymidine kinase (HSV-TK Mut2).

The modified T cells are given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the T cells can also cause GVHD, they are equipped with the suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of the disease.

Zalmoxis is being developed by MolMed S.p.A. The company said the treatment should become available in the first European market during the first half of 2017.

About conditional marketing authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

Under the provisions of the conditional marketing authorization for Zalmoxis, MolMed will be required to complete a post-marketing study aimed at confirming the clinical benefit of the treatment.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has accepted the ongoing phase 3 TK008 trial as a post-marketing confirmatory study.

Trials of Zalmoxis

The EC’s decision to grant Zalmoxis conditional marketing authorization was based on cumulative efficacy and safety data collected from patients enrolled in a phase 1/2 trial (TK007) and an ongoing phase 3 trial (TK008).

The Zalmoxis group comprised 30 patients from the TK007 trial and 15 patients from the experimental arm of the TK008 trial. The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, and the TK008 trial is enrolling haplo-HSCT recipients with high-risk acute leukemia.

The data thus far have indicated that Zalmoxis can provide rapid immune reconstitution, an anti-leukemia effect, and complete control of GVHD, in the absence of any post-transplant immunosuppression.

Overall, these effects led to a clinically meaningful increase in survival rates in Zalmoxis-treated patients, when compared to historical controls from the European Society for Blood and Marrow Transplantation (EBMT) database.

The only adverse event related to Zalmoxis treatment was GVHD, which was fully resolved by the activation of the suicide gene system with ganciclovir treatment, without any GVHD-related death.

Detailed results of this analysis are set to be presented during the MolMed-sponsored symposium “A new era of haplo-transplantation” at the EBMT International Transplant Course, which is scheduled to take place September 9-11 in Barcelona, Spain.

T cells

Image by NIAID

The European Commission (EC) has granted conditional marketing authorization for an immunogene therapy known as Zalmoxis.

This means Zalmoxis can be marketed in the European Economic Area as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults with high-risk hematologic malignancies who are receiving a haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Zalmoxis consists of allogeneic T cells genetically modified to express both a truncated form of the human low-affinity nerve growth factor receptor (ΔLNGFR), as a cell-surface selectable marker, and the suicide gene herpes simplex I virus thymidine kinase (HSV-TK Mut2).

The modified T cells are given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the T cells can also cause GVHD, they are equipped with the suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of the disease.

Zalmoxis is being developed by MolMed S.p.A. The company said the treatment should become available in the first European market during the first half of 2017.

About conditional marketing authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

Under the provisions of the conditional marketing authorization for Zalmoxis, MolMed will be required to complete a post-marketing study aimed at confirming the clinical benefit of the treatment.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has accepted the ongoing phase 3 TK008 trial as a post-marketing confirmatory study.

Trials of Zalmoxis

The EC’s decision to grant Zalmoxis conditional marketing authorization was based on cumulative efficacy and safety data collected from patients enrolled in a phase 1/2 trial (TK007) and an ongoing phase 3 trial (TK008).

The Zalmoxis group comprised 30 patients from the TK007 trial and 15 patients from the experimental arm of the TK008 trial. The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, and the TK008 trial is enrolling haplo-HSCT recipients with high-risk acute leukemia.

The data thus far have indicated that Zalmoxis can provide rapid immune reconstitution, an anti-leukemia effect, and complete control of GVHD, in the absence of any post-transplant immunosuppression.

Overall, these effects led to a clinically meaningful increase in survival rates in Zalmoxis-treated patients, when compared to historical controls from the European Society for Blood and Marrow Transplantation (EBMT) database.

The only adverse event related to Zalmoxis treatment was GVHD, which was fully resolved by the activation of the suicide gene system with ganciclovir treatment, without any GVHD-related death.

Detailed results of this analysis are set to be presented during the MolMed-sponsored symposium “A new era of haplo-transplantation” at the EBMT International Transplant Course, which is scheduled to take place September 9-11 in Barcelona, Spain.

T cells

Image by NIAID

The European Commission (EC) has granted conditional marketing authorization for an immunogene therapy known as Zalmoxis.

This means Zalmoxis can be marketed in the European Economic Area as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults with high-risk hematologic malignancies who are receiving a haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Zalmoxis consists of allogeneic T cells genetically modified to express both a truncated form of the human low-affinity nerve growth factor receptor (ΔLNGFR), as a cell-surface selectable marker, and the suicide gene herpes simplex I virus thymidine kinase (HSV-TK Mut2).

The modified T cells are given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the T cells can also cause GVHD, they are equipped with the suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of the disease.

Zalmoxis is being developed by MolMed S.p.A. The company said the treatment should become available in the first European market during the first half of 2017.

About conditional marketing authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

Under the provisions of the conditional marketing authorization for Zalmoxis, MolMed will be required to complete a post-marketing study aimed at confirming the clinical benefit of the treatment.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has accepted the ongoing phase 3 TK008 trial as a post-marketing confirmatory study.

Trials of Zalmoxis

The EC’s decision to grant Zalmoxis conditional marketing authorization was based on cumulative efficacy and safety data collected from patients enrolled in a phase 1/2 trial (TK007) and an ongoing phase 3 trial (TK008).

The Zalmoxis group comprised 30 patients from the TK007 trial and 15 patients from the experimental arm of the TK008 trial. The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, and the TK008 trial is enrolling haplo-HSCT recipients with high-risk acute leukemia.

The data thus far have indicated that Zalmoxis can provide rapid immune reconstitution, an anti-leukemia effect, and complete control of GVHD, in the absence of any post-transplant immunosuppression.

Overall, these effects led to a clinically meaningful increase in survival rates in Zalmoxis-treated patients, when compared to historical controls from the European Society for Blood and Marrow Transplantation (EBMT) database.

The only adverse event related to Zalmoxis treatment was GVHD, which was fully resolved by the activation of the suicide gene system with ganciclovir treatment, without any GVHD-related death.

Detailed results of this analysis are set to be presented during the MolMed-sponsored symposium “A new era of haplo-transplantation” at the EBMT International Transplant Course, which is scheduled to take place September 9-11 in Barcelona, Spain.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

Breast density is an important factor in determining the appropriate screening intervals for mammography after age 50 years, according to a report published online Aug. 22 in Annals of Internal Medicine.

Researchers from the Cancer Intervention and Surveillance Modeling Network, collaborating with the Breast Cancer Surveillance Consortium, assessed three separate, well-established microsimulation models that used different structures and underlying assumptions but the same data input to estimate the benefits and harms of various screening intervals. They applied the models to two hypothetical populations: Women aged 50 years and older who were initiating screening for the first time and women aged 65 years who had undergone biennial screening since age 50 years.

Catherine Yeulet/©Thinkstock

The models incorporated national data regarding breast cancer incidence, treatment efficacy, and survival. They assessed patient risk by including numerous factors, such as menopausal status, obesity status, age at menarche, nulliparity, and previous biopsy results, but didn’t include family history or genetic testing results. Screening strategies were compared among four possible breast-density levels, according to the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS).

The principal finding was that two factors – breast density and risk for breast cancer – were key to determining the optimal screening interval. The optimal interval was the one that would yield the highest number of benefits (breast cancer deaths averted, life-years gained, and quality-adjusted life-years gained) while yielding the lowest number of harms (false-positive mammograms, benign biopsies, and overdiagnosis).

“For average-risk women in low-density subgroups, who comprise a large portion of the population, triennial screening provides a reasonable balance of benefits and harms and is cost effective. Annual screening has a favorable balance of benefits and harms and would be considered cost effective for subgroups of women ... with risk levels that are two to four times the average and with heterogeneously or extremely dense breasts,” the researchers wrote (Ann.Intern Med. 2016 Aug 22. doi: 10.7326/M16-0476).

After age 50 years, annual mammography was more beneficial than harmful only in two subgroups of women: those with greater breast density and those with higher risk for breast cancer. Such women are estimated to comprise less than 1% of the general population at both age 50 years and age 65 years. In contrast, biennial and even triennial mammography yielded fewer false-positives and fewer biopsies for average-risk women with low-density breasts without affecting the number of breast cancer deaths averted, the researchers noted.

The study was supported by grants from the National Institutes of Health and several state public health departments and cancer registries in the United States. The researchers reported receiving grants and other support from the NIH, the American Society of Breast Surgeons, Renaissance Rx, Ally Clinical Diagnostics, the Netherlands National Institute for Public Health and the Environment, SCOR Global Risk Center, and Genomic Health Canada.

Breast density is an important factor in determining the appropriate screening intervals for mammography after age 50 years, according to a report published online Aug. 22 in Annals of Internal Medicine.

Researchers from the Cancer Intervention and Surveillance Modeling Network, collaborating with the Breast Cancer Surveillance Consortium, assessed three separate, well-established microsimulation models that used different structures and underlying assumptions but the same data input to estimate the benefits and harms of various screening intervals. They applied the models to two hypothetical populations: Women aged 50 years and older who were initiating screening for the first time and women aged 65 years who had undergone biennial screening since age 50 years.

Catherine Yeulet/©Thinkstock

The models incorporated national data regarding breast cancer incidence, treatment efficacy, and survival. They assessed patient risk by including numerous factors, such as menopausal status, obesity status, age at menarche, nulliparity, and previous biopsy results, but didn’t include family history or genetic testing results. Screening strategies were compared among four possible breast-density levels, according to the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS).

The principal finding was that two factors – breast density and risk for breast cancer – were key to determining the optimal screening interval. The optimal interval was the one that would yield the highest number of benefits (breast cancer deaths averted, life-years gained, and quality-adjusted life-years gained) while yielding the lowest number of harms (false-positive mammograms, benign biopsies, and overdiagnosis).

“For average-risk women in low-density subgroups, who comprise a large portion of the population, triennial screening provides a reasonable balance of benefits and harms and is cost effective. Annual screening has a favorable balance of benefits and harms and would be considered cost effective for subgroups of women ... with risk levels that are two to four times the average and with heterogeneously or extremely dense breasts,” the researchers wrote (Ann.Intern Med. 2016 Aug 22. doi: 10.7326/M16-0476).

After age 50 years, annual mammography was more beneficial than harmful only in two subgroups of women: those with greater breast density and those with higher risk for breast cancer. Such women are estimated to comprise less than 1% of the general population at both age 50 years and age 65 years. In contrast, biennial and even triennial mammography yielded fewer false-positives and fewer biopsies for average-risk women with low-density breasts without affecting the number of breast cancer deaths averted, the researchers noted.

The study was supported by grants from the National Institutes of Health and several state public health departments and cancer registries in the United States. The researchers reported receiving grants and other support from the NIH, the American Society of Breast Surgeons, Renaissance Rx, Ally Clinical Diagnostics, the Netherlands National Institute for Public Health and the Environment, SCOR Global Risk Center, and Genomic Health Canada.

Breast density is an important factor in determining the appropriate screening intervals for mammography after age 50 years, according to a report published online Aug. 22 in Annals of Internal Medicine.

Researchers from the Cancer Intervention and Surveillance Modeling Network, collaborating with the Breast Cancer Surveillance Consortium, assessed three separate, well-established microsimulation models that used different structures and underlying assumptions but the same data input to estimate the benefits and harms of various screening intervals. They applied the models to two hypothetical populations: Women aged 50 years and older who were initiating screening for the first time and women aged 65 years who had undergone biennial screening since age 50 years.

Catherine Yeulet/©Thinkstock

The models incorporated national data regarding breast cancer incidence, treatment efficacy, and survival. They assessed patient risk by including numerous factors, such as menopausal status, obesity status, age at menarche, nulliparity, and previous biopsy results, but didn’t include family history or genetic testing results. Screening strategies were compared among four possible breast-density levels, according to the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS).

The principal finding was that two factors – breast density and risk for breast cancer – were key to determining the optimal screening interval. The optimal interval was the one that would yield the highest number of benefits (breast cancer deaths averted, life-years gained, and quality-adjusted life-years gained) while yielding the lowest number of harms (false-positive mammograms, benign biopsies, and overdiagnosis).

“For average-risk women in low-density subgroups, who comprise a large portion of the population, triennial screening provides a reasonable balance of benefits and harms and is cost effective. Annual screening has a favorable balance of benefits and harms and would be considered cost effective for subgroups of women ... with risk levels that are two to four times the average and with heterogeneously or extremely dense breasts,” the researchers wrote (Ann.Intern Med. 2016 Aug 22. doi: 10.7326/M16-0476).

After age 50 years, annual mammography was more beneficial than harmful only in two subgroups of women: those with greater breast density and those with higher risk for breast cancer. Such women are estimated to comprise less than 1% of the general population at both age 50 years and age 65 years. In contrast, biennial and even triennial mammography yielded fewer false-positives and fewer biopsies for average-risk women with low-density breasts without affecting the number of breast cancer deaths averted, the researchers noted.

The study was supported by grants from the National Institutes of Health and several state public health departments and cancer registries in the United States. The researchers reported receiving grants and other support from the NIH, the American Society of Breast Surgeons, Renaissance Rx, Ally Clinical Diagnostics, the Netherlands National Institute for Public Health and the Environment, SCOR Global Risk Center, and Genomic Health Canada.

The struggles with the State of Ohio Board of Pharmacy continue. The pharmacy board reopened its comment period for 2 weeks and received many comments from multiple physicians, organizations, and patients who would be adversely affected by the Board’s move to hold physicians’ offices to the same standard as compounding pharmacies. This was the topic of my recent column, in which I pointed out that as a result, “any practitioners who reconstitute any drug in their offices is considered to be a compounding pharmacy, ordered to pay compounding pharmacy registration fees ($112 yearly), and to undergo the same inspections as compounding pharmacies”.

At their last meeting, the pharmacy board members made a few minor changes, but practitioners will still have to throw out their neurotoxins after 1-6 hours (the exact time is still under debate). Incidentally, I have spoken to all three neurotoxin manufacturers, and they have no interest in adding preservative to their products or in bringing out smaller unit dose packaging. These regulations will have broad impact across the house of medicine because many specialties use neurotoxin.

You should know the back story behind all of this, and how the house of medicine came to this sad place.

About 20 years ago, pain control became a cause célèbre in medicine championed by no less than the World Health Organization. Numerous publications, thought leaders, and policy wonks decried the inadequacy of pain control both in and out of the hospital. It was explained loud and long that patients should have their pain controlled and that physicians fell short if they did not do so, never mind that there is no quantifiable way to measure pain. Further, it was explained that patients in severe pain did not become addicted to narcotics. And the Joint Commission heralded pain control as “the fifth vital sign.”

Where are these thought leaders now?

Graded on responsiveness to patients’ pain and the results of patient surveys on pain control, physicians grudgingly opened the narcotic floodgates and large quantities of prescription narcotics hit the streets. Admittedly, some were written by bad doctors running “pill mills,” but other supplies were diverted by producers, pharmacists, pharmacies, and pharmacy technicians. Hundreds of thousands of Americans became addicted to prescription narcotics, but overdoses were infrequent because there was a unit dose on the street.

Then the medical pendulum swung back, and it was decided that there was too much pain medicine on the streets. The narcotic supply spigots were tightened sharply by the Drug Enforcement Administration, medical boards, and legislatures. It became hard for drug-seeking patients to fill multiple prescriptions, pill mills were shut down, doctors were encouraged to prescribe minimum dosages of narcotic pain relievers, and the price of the unit dose shot up on the street. The patterns of abuse and addiction shifted as heroin became cheaper and more readily available, but hard to dose, particularly when Mexican fentanyl was being sold as “heroin.” Unable to judge the dose of illicitly obtained drugs, addicts began overdosing and dying all over America.

Angry, bereaved family members demanded an accounting for the addiction and deaths of their relatives. Heat was applied to politicians, and a “culprit” was found, physicians! Physicians had made these drugs available and caused all of these people to be addicted!

And thus began the political ascendancy of the pharmacy board, whose members claimed clean hands in this affair. Keen to expand their scope of practice, pharmacists have been trying to find a way into clinical medicine for years. The pharmacy board offered their expertise, and politicians angry at doctors were willing to give the pharmacists’ recommendations a try.

Last year in Ohio, the legislature passed a huge budget reconciliation bill with language tucked in it that authorized the pharmacy board to regulate buprenorphine and other dangerous drugs. The obvious reading of this authority would be that pharmacists were supposed to regulate compounding pharmacies, like the one that produced tainted steroid injections that resulted in 64 deaths in 2012.The regulation is so vague, however, that it could be construed that pharmacists were supposed to regulate everyone in the state, especially since the pharmacy board unilaterally moved to define “dangerous” as any prescription drug. This puts all of medicine in play. The board then declared that it would apply U.S. Pharmacopeial Convention standards (those used for compounding pharmacies) to all physician offices and declared that reconstitution of any drug is considered to be compounding.

To consider physician’s offices as compounding pharmacies is absurd and will degrade patient care by increasing expense and denying access to treatments. Physicians have made and applied individual customized medications to their patients since Galen. It is an integral part of the practice of medicine and has not suddenly become the practice of pharmacy. Using this logic, pharmacists, who have recently won the right to administer vaccinations, should obtain special licenses from the state medical board, since injecting medications is clearly in the purview of medical practice. Physicians have not been killing patients by running dirty compounding pharmacies, pharmacists have. Good, clean up the compounding pharmacies! But applying these compounding rules to physicians’ offices will not save any lives.

This battle has just been joined. The American Medical Association recently passed a resolution declaring that physician compounding should be regulated by state medical boards. This action is most helpful, and another reason for you to join and support the AMA. If you practice in Ohio, you should join the Ohio State Medical Association post haste. They are a big dog in the Ohio legislature, and your membership will influence their efforts.

I hope the Ohio governor’s Common Sense Initiative Office will convene a joint meeting that allows physicians, especially dermatologists, to demonstrate the absurdity of these rules, and their potentially destructive effects on patient care. However, I do not expect the pharmacy board to readily give up this power. Ultimately, the language in the legislative code must add two words after the word “compounding.” The words to be added are “by pharmacists.”

These rules may have to be stayed by a legal injunction. If the legislation is not clarified, a lawsuit against the pharmacy board based on restraint of trade should be successful.

Be vigilant, and watch your state legislatures. Just recently, the pharmacy board of North Dakota has made the same power grab. Stay tuned, as this struggle has national implications.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

The struggles with the State of Ohio Board of Pharmacy continue. The pharmacy board reopened its comment period for 2 weeks and received many comments from multiple physicians, organizations, and patients who would be adversely affected by the Board’s move to hold physicians’ offices to the same standard as compounding pharmacies. This was the topic of my recent column, in which I pointed out that as a result, “any practitioners who reconstitute any drug in their offices is considered to be a compounding pharmacy, ordered to pay compounding pharmacy registration fees ($112 yearly), and to undergo the same inspections as compounding pharmacies”.

At their last meeting, the pharmacy board members made a few minor changes, but practitioners will still have to throw out their neurotoxins after 1-6 hours (the exact time is still under debate). Incidentally, I have spoken to all three neurotoxin manufacturers, and they have no interest in adding preservative to their products or in bringing out smaller unit dose packaging. These regulations will have broad impact across the house of medicine because many specialties use neurotoxin.

You should know the back story behind all of this, and how the house of medicine came to this sad place.

About 20 years ago, pain control became a cause célèbre in medicine championed by no less than the World Health Organization. Numerous publications, thought leaders, and policy wonks decried the inadequacy of pain control both in and out of the hospital. It was explained loud and long that patients should have their pain controlled and that physicians fell short if they did not do so, never mind that there is no quantifiable way to measure pain. Further, it was explained that patients in severe pain did not become addicted to narcotics. And the Joint Commission heralded pain control as “the fifth vital sign.”

Where are these thought leaders now?

Graded on responsiveness to patients’ pain and the results of patient surveys on pain control, physicians grudgingly opened the narcotic floodgates and large quantities of prescription narcotics hit the streets. Admittedly, some were written by bad doctors running “pill mills,” but other supplies were diverted by producers, pharmacists, pharmacies, and pharmacy technicians. Hundreds of thousands of Americans became addicted to prescription narcotics, but overdoses were infrequent because there was a unit dose on the street.

Then the medical pendulum swung back, and it was decided that there was too much pain medicine on the streets. The narcotic supply spigots were tightened sharply by the Drug Enforcement Administration, medical boards, and legislatures. It became hard for drug-seeking patients to fill multiple prescriptions, pill mills were shut down, doctors were encouraged to prescribe minimum dosages of narcotic pain relievers, and the price of the unit dose shot up on the street. The patterns of abuse and addiction shifted as heroin became cheaper and more readily available, but hard to dose, particularly when Mexican fentanyl was being sold as “heroin.” Unable to judge the dose of illicitly obtained drugs, addicts began overdosing and dying all over America.

Angry, bereaved family members demanded an accounting for the addiction and deaths of their relatives. Heat was applied to politicians, and a “culprit” was found, physicians! Physicians had made these drugs available and caused all of these people to be addicted!

And thus began the political ascendancy of the pharmacy board, whose members claimed clean hands in this affair. Keen to expand their scope of practice, pharmacists have been trying to find a way into clinical medicine for years. The pharmacy board offered their expertise, and politicians angry at doctors were willing to give the pharmacists’ recommendations a try.

Last year in Ohio, the legislature passed a huge budget reconciliation bill with language tucked in it that authorized the pharmacy board to regulate buprenorphine and other dangerous drugs. The obvious reading of this authority would be that pharmacists were supposed to regulate compounding pharmacies, like the one that produced tainted steroid injections that resulted in 64 deaths in 2012.The regulation is so vague, however, that it could be construed that pharmacists were supposed to regulate everyone in the state, especially since the pharmacy board unilaterally moved to define “dangerous” as any prescription drug. This puts all of medicine in play. The board then declared that it would apply U.S. Pharmacopeial Convention standards (those used for compounding pharmacies) to all physician offices and declared that reconstitution of any drug is considered to be compounding.

To consider physician’s offices as compounding pharmacies is absurd and will degrade patient care by increasing expense and denying access to treatments. Physicians have made and applied individual customized medications to their patients since Galen. It is an integral part of the practice of medicine and has not suddenly become the practice of pharmacy. Using this logic, pharmacists, who have recently won the right to administer vaccinations, should obtain special licenses from the state medical board, since injecting medications is clearly in the purview of medical practice. Physicians have not been killing patients by running dirty compounding pharmacies, pharmacists have. Good, clean up the compounding pharmacies! But applying these compounding rules to physicians’ offices will not save any lives.

This battle has just been joined. The American Medical Association recently passed a resolution declaring that physician compounding should be regulated by state medical boards. This action is most helpful, and another reason for you to join and support the AMA. If you practice in Ohio, you should join the Ohio State Medical Association post haste. They are a big dog in the Ohio legislature, and your membership will influence their efforts.

I hope the Ohio governor’s Common Sense Initiative Office will convene a joint meeting that allows physicians, especially dermatologists, to demonstrate the absurdity of these rules, and their potentially destructive effects on patient care. However, I do not expect the pharmacy board to readily give up this power. Ultimately, the language in the legislative code must add two words after the word “compounding.” The words to be added are “by pharmacists.”

These rules may have to be stayed by a legal injunction. If the legislation is not clarified, a lawsuit against the pharmacy board based on restraint of trade should be successful.

Be vigilant, and watch your state legislatures. Just recently, the pharmacy board of North Dakota has made the same power grab. Stay tuned, as this struggle has national implications.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

The struggles with the State of Ohio Board of Pharmacy continue. The pharmacy board reopened its comment period for 2 weeks and received many comments from multiple physicians, organizations, and patients who would be adversely affected by the Board’s move to hold physicians’ offices to the same standard as compounding pharmacies. This was the topic of my recent column, in which I pointed out that as a result, “any practitioners who reconstitute any drug in their offices is considered to be a compounding pharmacy, ordered to pay compounding pharmacy registration fees ($112 yearly), and to undergo the same inspections as compounding pharmacies”.

At their last meeting, the pharmacy board members made a few minor changes, but practitioners will still have to throw out their neurotoxins after 1-6 hours (the exact time is still under debate). Incidentally, I have spoken to all three neurotoxin manufacturers, and they have no interest in adding preservative to their products or in bringing out smaller unit dose packaging. These regulations will have broad impact across the house of medicine because many specialties use neurotoxin.

You should know the back story behind all of this, and how the house of medicine came to this sad place.

About 20 years ago, pain control became a cause célèbre in medicine championed by no less than the World Health Organization. Numerous publications, thought leaders, and policy wonks decried the inadequacy of pain control both in and out of the hospital. It was explained loud and long that patients should have their pain controlled and that physicians fell short if they did not do so, never mind that there is no quantifiable way to measure pain. Further, it was explained that patients in severe pain did not become addicted to narcotics. And the Joint Commission heralded pain control as “the fifth vital sign.”

Where are these thought leaders now?

Graded on responsiveness to patients’ pain and the results of patient surveys on pain control, physicians grudgingly opened the narcotic floodgates and large quantities of prescription narcotics hit the streets. Admittedly, some were written by bad doctors running “pill mills,” but other supplies were diverted by producers, pharmacists, pharmacies, and pharmacy technicians. Hundreds of thousands of Americans became addicted to prescription narcotics, but overdoses were infrequent because there was a unit dose on the street.

Then the medical pendulum swung back, and it was decided that there was too much pain medicine on the streets. The narcotic supply spigots were tightened sharply by the Drug Enforcement Administration, medical boards, and legislatures. It became hard for drug-seeking patients to fill multiple prescriptions, pill mills were shut down, doctors were encouraged to prescribe minimum dosages of narcotic pain relievers, and the price of the unit dose shot up on the street. The patterns of abuse and addiction shifted as heroin became cheaper and more readily available, but hard to dose, particularly when Mexican fentanyl was being sold as “heroin.” Unable to judge the dose of illicitly obtained drugs, addicts began overdosing and dying all over America.

Angry, bereaved family members demanded an accounting for the addiction and deaths of their relatives. Heat was applied to politicians, and a “culprit” was found, physicians! Physicians had made these drugs available and caused all of these people to be addicted!

And thus began the political ascendancy of the pharmacy board, whose members claimed clean hands in this affair. Keen to expand their scope of practice, pharmacists have been trying to find a way into clinical medicine for years. The pharmacy board offered their expertise, and politicians angry at doctors were willing to give the pharmacists’ recommendations a try.

Last year in Ohio, the legislature passed a huge budget reconciliation bill with language tucked in it that authorized the pharmacy board to regulate buprenorphine and other dangerous drugs. The obvious reading of this authority would be that pharmacists were supposed to regulate compounding pharmacies, like the one that produced tainted steroid injections that resulted in 64 deaths in 2012.The regulation is so vague, however, that it could be construed that pharmacists were supposed to regulate everyone in the state, especially since the pharmacy board unilaterally moved to define “dangerous” as any prescription drug. This puts all of medicine in play. The board then declared that it would apply U.S. Pharmacopeial Convention standards (those used for compounding pharmacies) to all physician offices and declared that reconstitution of any drug is considered to be compounding.

To consider physician’s offices as compounding pharmacies is absurd and will degrade patient care by increasing expense and denying access to treatments. Physicians have made and applied individual customized medications to their patients since Galen. It is an integral part of the practice of medicine and has not suddenly become the practice of pharmacy. Using this logic, pharmacists, who have recently won the right to administer vaccinations, should obtain special licenses from the state medical board, since injecting medications is clearly in the purview of medical practice. Physicians have not been killing patients by running dirty compounding pharmacies, pharmacists have. Good, clean up the compounding pharmacies! But applying these compounding rules to physicians’ offices will not save any lives.

This battle has just been joined. The American Medical Association recently passed a resolution declaring that physician compounding should be regulated by state medical boards. This action is most helpful, and another reason for you to join and support the AMA. If you practice in Ohio, you should join the Ohio State Medical Association post haste. They are a big dog in the Ohio legislature, and your membership will influence their efforts.

I hope the Ohio governor’s Common Sense Initiative Office will convene a joint meeting that allows physicians, especially dermatologists, to demonstrate the absurdity of these rules, and their potentially destructive effects on patient care. However, I do not expect the pharmacy board to readily give up this power. Ultimately, the language in the legislative code must add two words after the word “compounding.” The words to be added are “by pharmacists.”

These rules may have to be stayed by a legal injunction. If the legislation is not clarified, a lawsuit against the pharmacy board based on restraint of trade should be successful.

Be vigilant, and watch your state legislatures. Just recently, the pharmacy board of North Dakota has made the same power grab. Stay tuned, as this struggle has national implications.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

Decades of research have revolutionized the care of many digestive disease patients. These patients, as well as everyone in the GI field – clinicians and researchers alike, have benefited from the discoveries of dedicated investigators, past and present. Creative young investigators are poised to make groundbreaking discoveries that will shape the future of gastroenterology. As the charitable arm of the AGA, the AGA Research Foundation provides a key source of funding at a critical juncture in a young researcher’s career.

“To continue to improve the diagnosis and treatment of digestive disease, we need innovative researchers with new approaches. This kind of scientific exploration has the potential to make a tremendous impact on the future of health care,” states Dr. Robert S. Sandler, chair of the AGA Research Foundation and AGA Legacy Society member.

By joining others in supporting the AGA Research Foundation, you will ensure that young investigators have opportunities to continue their life-saving work. Learn more or make a contribution at the AGA Research Foundation web site.

Join the AGA Legacy Society

The AGA Legacy Society honors individuals who have chosen to benefit the AGA Research Foundation through a significant current or planned gift. Research is made possible through their support. AGA Legacy Society members are showing their gratitude for what funding and research has brought to our specialty by giving back. Members of the AGA Legacy Society contribute $5,000 or more annually for five years to the AGA Research Foundation. Learn more about the AGA Legacy Society on the foundation’s website.

Decades of research have revolutionized the care of many digestive disease patients. These patients, as well as everyone in the GI field – clinicians and researchers alike, have benefited from the discoveries of dedicated investigators, past and present. Creative young investigators are poised to make groundbreaking discoveries that will shape the future of gastroenterology. As the charitable arm of the AGA, the AGA Research Foundation provides a key source of funding at a critical juncture in a young researcher’s career.

“To continue to improve the diagnosis and treatment of digestive disease, we need innovative researchers with new approaches. This kind of scientific exploration has the potential to make a tremendous impact on the future of health care,” states Dr. Robert S. Sandler, chair of the AGA Research Foundation and AGA Legacy Society member.

By joining others in supporting the AGA Research Foundation, you will ensure that young investigators have opportunities to continue their life-saving work. Learn more or make a contribution at the AGA Research Foundation web site.

Join the AGA Legacy Society

The AGA Legacy Society honors individuals who have chosen to benefit the AGA Research Foundation through a significant current or planned gift. Research is made possible through their support. AGA Legacy Society members are showing their gratitude for what funding and research has brought to our specialty by giving back. Members of the AGA Legacy Society contribute $5,000 or more annually for five years to the AGA Research Foundation. Learn more about the AGA Legacy Society on the foundation’s website.

Decades of research have revolutionized the care of many digestive disease patients. These patients, as well as everyone in the GI field – clinicians and researchers alike, have benefited from the discoveries of dedicated investigators, past and present. Creative young investigators are poised to make groundbreaking discoveries that will shape the future of gastroenterology. As the charitable arm of the AGA, the AGA Research Foundation provides a key source of funding at a critical juncture in a young researcher’s career.

“To continue to improve the diagnosis and treatment of digestive disease, we need innovative researchers with new approaches. This kind of scientific exploration has the potential to make a tremendous impact on the future of health care,” states Dr. Robert S. Sandler, chair of the AGA Research Foundation and AGA Legacy Society member.

By joining others in supporting the AGA Research Foundation, you will ensure that young investigators have opportunities to continue their life-saving work. Learn more or make a contribution at the AGA Research Foundation web site.

Join the AGA Legacy Society

The AGA Legacy Society honors individuals who have chosen to benefit the AGA Research Foundation through a significant current or planned gift. Research is made possible through their support. AGA Legacy Society members are showing their gratitude for what funding and research has brought to our specialty by giving back. Members of the AGA Legacy Society contribute $5,000 or more annually for five years to the AGA Research Foundation. Learn more about the AGA Legacy Society on the foundation’s website.