Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.

Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.

Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.

Dermatologists have become accustomed to reading about the associations of dermatologic disease with extracutaneous comorbidities (psoriasis certainly takes the lead). One may see the headline “Study finds increased risk for melanoma in female acne patients” and say “Sure, why not?” However, before we all jump on the association bandwagon, let’s better appreciate this finding.

A study published online January 8 in Cancer by Zhang et al followed 99,128 female nurses in the Nurses’ Health Study II cohort for 20 years. This cohort has been utilized for numerous prospective studies over the year. Even after adjusting for known risk factors, investigators discovered that women with a history of severe cystic teenage acne had a hazard ratio of 1.44 for melanoma. The authors replicated the association with an independent melanoma case-control study of 930 cases and 1026 controls, finding an odds ratio of 1.27. They also found that individuals with teenage acne were more likely to have nevi (52.7% vs 50.1% in the cohort study; 55.2% vs 45.1% in the control study).

These data points ultimately led the team to conclude that acne may serve as an independent risk factor for melanoma, attributing androgens in female acne as a possible and plausible explanation due to their known effect on telomere elongation; melanocytes with longer telomere lengths have more opportunity to develop mutations, which could lead to malignant transformation, as the extended length ultimately delays initiation of cellular senescence. The longer these cells are “awake,” more moles can form, which means more room for trouble.

What’s the issue?

The size of this cohort certainly gives credibility to the data and statistics presented. Although the study is powered very well by the numbers, it is a unique cohort because all participants were nurses, narrowing down the demographics to some degree given general patterns, behaviors, and backgrounds when it comes to this group, an issue that has been previously raised with using this cohort. That said, more research is certainly warranted to elucidate the proposed mechanism and further clarify the association.

From a purely clinical standpoint, this paper is powerful ammo that can be used in our war against skin cancer. This very large cohort probably does not follow the American Academy of Dermatology guidelines for sun protection, skin cancer prevention, and surveillance. It could be a nice tidbit for patients at the end of your spiel on acne and then work in the photoprotection discussion, something we haven’t been the best at according to a recent study published in JAMA Dermatology (JAMA Dermatol. 2014;150:51-55)! Would it be such a bad thing if this paper helped us encourage all women with moderate to severe acne to undertake more effective sun-safe behaviors and to visit their dermatologist every year for total-body skin examinations?

We want to know your views! Tell us what you think.

Dermatologists have become accustomed to reading about the associations of dermatologic disease with extracutaneous comorbidities (psoriasis certainly takes the lead). One may see the headline “Study finds increased risk for melanoma in female acne patients” and say “Sure, why not?” However, before we all jump on the association bandwagon, let’s better appreciate this finding.

A study published online January 8 in Cancer by Zhang et al followed 99,128 female nurses in the Nurses’ Health Study II cohort for 20 years. This cohort has been utilized for numerous prospective studies over the year. Even after adjusting for known risk factors, investigators discovered that women with a history of severe cystic teenage acne had a hazard ratio of 1.44 for melanoma. The authors replicated the association with an independent melanoma case-control study of 930 cases and 1026 controls, finding an odds ratio of 1.27. They also found that individuals with teenage acne were more likely to have nevi (52.7% vs 50.1% in the cohort study; 55.2% vs 45.1% in the control study).

These data points ultimately led the team to conclude that acne may serve as an independent risk factor for melanoma, attributing androgens in female acne as a possible and plausible explanation due to their known effect on telomere elongation; melanocytes with longer telomere lengths have more opportunity to develop mutations, which could lead to malignant transformation, as the extended length ultimately delays initiation of cellular senescence. The longer these cells are “awake,” more moles can form, which means more room for trouble.

What’s the issue?

The size of this cohort certainly gives credibility to the data and statistics presented. Although the study is powered very well by the numbers, it is a unique cohort because all participants were nurses, narrowing down the demographics to some degree given general patterns, behaviors, and backgrounds when it comes to this group, an issue that has been previously raised with using this cohort. That said, more research is certainly warranted to elucidate the proposed mechanism and further clarify the association.

From a purely clinical standpoint, this paper is powerful ammo that can be used in our war against skin cancer. This very large cohort probably does not follow the American Academy of Dermatology guidelines for sun protection, skin cancer prevention, and surveillance. It could be a nice tidbit for patients at the end of your spiel on acne and then work in the photoprotection discussion, something we haven’t been the best at according to a recent study published in JAMA Dermatology (JAMA Dermatol. 2014;150:51-55)! Would it be such a bad thing if this paper helped us encourage all women with moderate to severe acne to undertake more effective sun-safe behaviors and to visit their dermatologist every year for total-body skin examinations?

We want to know your views! Tell us what you think.

Dermatologists have become accustomed to reading about the associations of dermatologic disease with extracutaneous comorbidities (psoriasis certainly takes the lead). One may see the headline “Study finds increased risk for melanoma in female acne patients” and say “Sure, why not?” However, before we all jump on the association bandwagon, let’s better appreciate this finding.

A study published online January 8 in Cancer by Zhang et al followed 99,128 female nurses in the Nurses’ Health Study II cohort for 20 years. This cohort has been utilized for numerous prospective studies over the year. Even after adjusting for known risk factors, investigators discovered that women with a history of severe cystic teenage acne had a hazard ratio of 1.44 for melanoma. The authors replicated the association with an independent melanoma case-control study of 930 cases and 1026 controls, finding an odds ratio of 1.27. They also found that individuals with teenage acne were more likely to have nevi (52.7% vs 50.1% in the cohort study; 55.2% vs 45.1% in the control study).

These data points ultimately led the team to conclude that acne may serve as an independent risk factor for melanoma, attributing androgens in female acne as a possible and plausible explanation due to their known effect on telomere elongation; melanocytes with longer telomere lengths have more opportunity to develop mutations, which could lead to malignant transformation, as the extended length ultimately delays initiation of cellular senescence. The longer these cells are “awake,” more moles can form, which means more room for trouble.

What’s the issue?

The size of this cohort certainly gives credibility to the data and statistics presented. Although the study is powered very well by the numbers, it is a unique cohort because all participants were nurses, narrowing down the demographics to some degree given general patterns, behaviors, and backgrounds when it comes to this group, an issue that has been previously raised with using this cohort. That said, more research is certainly warranted to elucidate the proposed mechanism and further clarify the association.

From a purely clinical standpoint, this paper is powerful ammo that can be used in our war against skin cancer. This very large cohort probably does not follow the American Academy of Dermatology guidelines for sun protection, skin cancer prevention, and surveillance. It could be a nice tidbit for patients at the end of your spiel on acne and then work in the photoprotection discussion, something we haven’t been the best at according to a recent study published in JAMA Dermatology (JAMA Dermatol. 2014;150:51-55)! Would it be such a bad thing if this paper helped us encourage all women with moderate to severe acne to undertake more effective sun-safe behaviors and to visit their dermatologist every year for total-body skin examinations?

We want to know your views! Tell us what you think.

NEW YORK - Coating on endovascular devices is associated with embolization and microvascular occlusion leading to purpura or livedo racemosa, according to a new report.

Dr. Alina Bridges, of the Department of Dermatology at Mayo Clinic in Rochester, Minnesota, said by email that the study was conducted "to make clinicians and pathologists aware of this underrecognized phenomenon of iatrogenic hydrophilic polymer gel embolization that can involve the skin and present with purpura."

The phenomenon "has distinctive microscopic morphology and potential for internal organ involvement," she added.

Endovascular devices commonly are coated with hydrophilic polymer gels to improve maneuverability and prevent vasospasm. However, there are reports of the coating embolizing, resulting

in severe reactions such as stroke, pulmonary infarction, and death.

Dr. Bridges and colleagues presented a case study of eight patients with livedo racemosa and purpura after an endovascular procedure. The patients had punch biopsies obtained with hematoxylin-eosin-stained sections.

The study subjects were between 58 and 81 years old, most were men and most had previous endovascular procedures and multiple comorbidities, according to an article online August 11 in the Journal of the American Academy of Dermatology.

In all but one patient, the cutaneous lesions were unilateral and all but two were asymptomatic. Six patients presented with livedo racemosa and two with purpura.

All cases demonstrated pauci-inflammatory occlusion in the mid-dermal and small superficial vessels. Likewise, histopathologic evidence was consistent with previously reported cases of emboli secondary to hydrophilic gel polymer.

There was no evidence of embolic sequela to the organs in three patients. However, one patient died of unknown reasons and four patients experienced postoperative complications including spinal cord ischemia, acute kidney injury, and cerebral infarction. In all cases, the cutaneous manifestations resolved without intervention.

The authors say they suspect the incidence of this type of embolization is underrecognized, especially with the common use of hydrophilic polymer gel coatings.

"This report highlights the importance of awareness of this rare iatrogenic complication and the importance of investigating a patient's clinical history to determine if there had been recent exposure to an intravascular device with a hydrophilic coating," Dr. Bridges said.

"While the use of polymer-coated devices offers several advantages, clinicians must be aware of their potential complications, including stroke, myocardial and pulmonary infarction, gangrene, and/or death," she said.

The authors reported no funding or conflicts of interest.

NEW YORK - Coating on endovascular devices is associated with embolization and microvascular occlusion leading to purpura or livedo racemosa, according to a new report.

Dr. Alina Bridges, of the Department of Dermatology at Mayo Clinic in Rochester, Minnesota, said by email that the study was conducted "to make clinicians and pathologists aware of this underrecognized phenomenon of iatrogenic hydrophilic polymer gel embolization that can involve the skin and present with purpura."

The phenomenon "has distinctive microscopic morphology and potential for internal organ involvement," she added.

Endovascular devices commonly are coated with hydrophilic polymer gels to improve maneuverability and prevent vasospasm. However, there are reports of the coating embolizing, resulting

in severe reactions such as stroke, pulmonary infarction, and death.

Dr. Bridges and colleagues presented a case study of eight patients with livedo racemosa and purpura after an endovascular procedure. The patients had punch biopsies obtained with hematoxylin-eosin-stained sections.

The study subjects were between 58 and 81 years old, most were men and most had previous endovascular procedures and multiple comorbidities, according to an article online August 11 in the Journal of the American Academy of Dermatology.

In all but one patient, the cutaneous lesions were unilateral and all but two were asymptomatic. Six patients presented with livedo racemosa and two with purpura.

All cases demonstrated pauci-inflammatory occlusion in the mid-dermal and small superficial vessels. Likewise, histopathologic evidence was consistent with previously reported cases of emboli secondary to hydrophilic gel polymer.

There was no evidence of embolic sequela to the organs in three patients. However, one patient died of unknown reasons and four patients experienced postoperative complications including spinal cord ischemia, acute kidney injury, and cerebral infarction. In all cases, the cutaneous manifestations resolved without intervention.

The authors say they suspect the incidence of this type of embolization is underrecognized, especially with the common use of hydrophilic polymer gel coatings.

"This report highlights the importance of awareness of this rare iatrogenic complication and the importance of investigating a patient's clinical history to determine if there had been recent exposure to an intravascular device with a hydrophilic coating," Dr. Bridges said.

"While the use of polymer-coated devices offers several advantages, clinicians must be aware of their potential complications, including stroke, myocardial and pulmonary infarction, gangrene, and/or death," she said.

The authors reported no funding or conflicts of interest.

NEW YORK - Coating on endovascular devices is associated with embolization and microvascular occlusion leading to purpura or livedo racemosa, according to a new report.

Dr. Alina Bridges, of the Department of Dermatology at Mayo Clinic in Rochester, Minnesota, said by email that the study was conducted "to make clinicians and pathologists aware of this underrecognized phenomenon of iatrogenic hydrophilic polymer gel embolization that can involve the skin and present with purpura."

The phenomenon "has distinctive microscopic morphology and potential for internal organ involvement," she added.

Endovascular devices commonly are coated with hydrophilic polymer gels to improve maneuverability and prevent vasospasm. However, there are reports of the coating embolizing, resulting

in severe reactions such as stroke, pulmonary infarction, and death.

Dr. Bridges and colleagues presented a case study of eight patients with livedo racemosa and purpura after an endovascular procedure. The patients had punch biopsies obtained with hematoxylin-eosin-stained sections.

The study subjects were between 58 and 81 years old, most were men and most had previous endovascular procedures and multiple comorbidities, according to an article online August 11 in the Journal of the American Academy of Dermatology.

In all but one patient, the cutaneous lesions were unilateral and all but two were asymptomatic. Six patients presented with livedo racemosa and two with purpura.

All cases demonstrated pauci-inflammatory occlusion in the mid-dermal and small superficial vessels. Likewise, histopathologic evidence was consistent with previously reported cases of emboli secondary to hydrophilic gel polymer.

There was no evidence of embolic sequela to the organs in three patients. However, one patient died of unknown reasons and four patients experienced postoperative complications including spinal cord ischemia, acute kidney injury, and cerebral infarction. In all cases, the cutaneous manifestations resolved without intervention.

The authors say they suspect the incidence of this type of embolization is underrecognized, especially with the common use of hydrophilic polymer gel coatings.

"This report highlights the importance of awareness of this rare iatrogenic complication and the importance of investigating a patient's clinical history to determine if there had been recent exposure to an intravascular device with a hydrophilic coating," Dr. Bridges said.

"While the use of polymer-coated devices offers several advantages, clinicians must be aware of their potential complications, including stroke, myocardial and pulmonary infarction, gangrene, and/or death," she said.

The authors reported no funding or conflicts of interest.

Patients with actinic keratosis who used UPF 50 sunscreen containing DNA repair enzymes improved significantly more on two measures of malignant progression than did those who used sunscreen alone, according to research published in the Journal of Drugs in Dermatology.

At 6 months, improvements in field cancerization and levels of cyclobutane pyrimidine dimers were significantly greater (P less than .001) for the sunscreen-plus-enzymes group compared with sunscreen-only patients, wrote Dr. Mauro Carducci of Centro Ortopedico di Quadrante in Omegna, Italy, and his associates.

The study is the first of its type to directly compare the clinical effects of two such topicals, the investigators wrote. The findings set the stage for longer, larger trials that are powered to assess the risk of progression to squamous cell carcinoma, they added.

©Stockbyte/ thinkstockphotos.com

For the study, 28 patients with AK were randomly assigned to use SPF 50 sunscreen alone or a formula that contained 1% photolyase from Anacystis nidulans and 1% endonuclease from Micrococcus luteus. Patients applied 2 mg/cm² of sunscreen to treatment areas that contained 4-10 AKs. They were not allowed to use other topicals during the trial or for 2 weeks beforehand.

All of the patients were white and aged older than 65 years; three-quarters were men. The investigators used fluorescence diagnostics with methylaminolaevulinate to measure field cancerization, and analyzed skin biopsies to quantify CPD levels (J Drugs Dermatol. 2015;14[9]:986-90.).

Hyperkeratosis improved the same amount in both groups at month 6, according to the researchers. But field cancerizations dropped 29% from baseline in the sunscreen-plus-enzymes group, compared with a 10% decrease with sunscreen alone (P less than .0001). Likewise, CPD levels fell 61% from baseline in the sunscreen-plus-enzymes group compared with a 35% drop with sunscreen alone (P less than .0001).

Despite those significant differences, the study was not powered to detect differences in the risk of transformation to SCC, the researchers cautioned.

Biodue S.p.A. provided the methyl aminolevulinate used in the study. Dr. Enzo Emanuele, the study’s senior author, is a major shareholder of Living Research S.A.S., a privately held biomedical research organization that provided funding for the work. The other researchers reported no conflicts of interest.

Patients with actinic keratosis who used UPF 50 sunscreen containing DNA repair enzymes improved significantly more on two measures of malignant progression than did those who used sunscreen alone, according to research published in the Journal of Drugs in Dermatology.

At 6 months, improvements in field cancerization and levels of cyclobutane pyrimidine dimers were significantly greater (P less than .001) for the sunscreen-plus-enzymes group compared with sunscreen-only patients, wrote Dr. Mauro Carducci of Centro Ortopedico di Quadrante in Omegna, Italy, and his associates.

The study is the first of its type to directly compare the clinical effects of two such topicals, the investigators wrote. The findings set the stage for longer, larger trials that are powered to assess the risk of progression to squamous cell carcinoma, they added.

©Stockbyte/ thinkstockphotos.com

For the study, 28 patients with AK were randomly assigned to use SPF 50 sunscreen alone or a formula that contained 1% photolyase from Anacystis nidulans and 1% endonuclease from Micrococcus luteus. Patients applied 2 mg/cm² of sunscreen to treatment areas that contained 4-10 AKs. They were not allowed to use other topicals during the trial or for 2 weeks beforehand.

All of the patients were white and aged older than 65 years; three-quarters were men. The investigators used fluorescence diagnostics with methylaminolaevulinate to measure field cancerization, and analyzed skin biopsies to quantify CPD levels (J Drugs Dermatol. 2015;14[9]:986-90.).

Hyperkeratosis improved the same amount in both groups at month 6, according to the researchers. But field cancerizations dropped 29% from baseline in the sunscreen-plus-enzymes group, compared with a 10% decrease with sunscreen alone (P less than .0001). Likewise, CPD levels fell 61% from baseline in the sunscreen-plus-enzymes group compared with a 35% drop with sunscreen alone (P less than .0001).

Despite those significant differences, the study was not powered to detect differences in the risk of transformation to SCC, the researchers cautioned.

Biodue S.p.A. provided the methyl aminolevulinate used in the study. Dr. Enzo Emanuele, the study’s senior author, is a major shareholder of Living Research S.A.S., a privately held biomedical research organization that provided funding for the work. The other researchers reported no conflicts of interest.

Patients with actinic keratosis who used UPF 50 sunscreen containing DNA repair enzymes improved significantly more on two measures of malignant progression than did those who used sunscreen alone, according to research published in the Journal of Drugs in Dermatology.

At 6 months, improvements in field cancerization and levels of cyclobutane pyrimidine dimers were significantly greater (P less than .001) for the sunscreen-plus-enzymes group compared with sunscreen-only patients, wrote Dr. Mauro Carducci of Centro Ortopedico di Quadrante in Omegna, Italy, and his associates.

The study is the first of its type to directly compare the clinical effects of two such topicals, the investigators wrote. The findings set the stage for longer, larger trials that are powered to assess the risk of progression to squamous cell carcinoma, they added.

©Stockbyte/ thinkstockphotos.com

For the study, 28 patients with AK were randomly assigned to use SPF 50 sunscreen alone or a formula that contained 1% photolyase from Anacystis nidulans and 1% endonuclease from Micrococcus luteus. Patients applied 2 mg/cm² of sunscreen to treatment areas that contained 4-10 AKs. They were not allowed to use other topicals during the trial or for 2 weeks beforehand.

All of the patients were white and aged older than 65 years; three-quarters were men. The investigators used fluorescence diagnostics with methylaminolaevulinate to measure field cancerization, and analyzed skin biopsies to quantify CPD levels (J Drugs Dermatol. 2015;14[9]:986-90.).

Hyperkeratosis improved the same amount in both groups at month 6, according to the researchers. But field cancerizations dropped 29% from baseline in the sunscreen-plus-enzymes group, compared with a 10% decrease with sunscreen alone (P less than .0001). Likewise, CPD levels fell 61% from baseline in the sunscreen-plus-enzymes group compared with a 35% drop with sunscreen alone (P less than .0001).

Despite those significant differences, the study was not powered to detect differences in the risk of transformation to SCC, the researchers cautioned.

Biodue S.p.A. provided the methyl aminolevulinate used in the study. Dr. Enzo Emanuele, the study’s senior author, is a major shareholder of Living Research S.A.S., a privately held biomedical research organization that provided funding for the work. The other researchers reported no conflicts of interest.

Slide showing LSCs

Image by Robert Paulson

Two groups of researchers have reported results that help explain how leukemia resists treatment with BET inhibitors.

One group was able to grow and maintain leukemia stem cells (LSCs) in vitro, and their subsequent experiments showed how LSCs react to BET inhibition.

The other group found evidence to suggest that by measuring Wnt signaling markers, we might be able to predict which patients will respond to BET inhibition.

Both groups described their research in letters to Nature.

“[T]he risk of resistance developing is common in any cancer treatment,” said Mark Dawson, PhD, a researcher at Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia and an author of the LSC study.

“Knowing precisely how that happens in advance puts us one step ahead in outmaneuvering the disease. Being able to grow and maintain leukemia

stem cells in vitro also gives us unprecedented access and insight into how they work so we can find new and better ways to target and destroy them.”

In their study, Dr Dawson and his colleagues assessed BET inhibitor resistance in a model of acute myeloid leukemia.

The team transduced murine hematopoietic stem and progenitor cells with MLL–AF9 and treated the cells with the BET inhibitor I-BET or dimethylsulfoxide (vehicle). They then isolated individual blast colonies to generate 4 vehicle-treated and 5 I-BET-resistant cell lines.

The researchers found that resistance to I-BET also conferred resistance to the chemically distinct BET inhibitor JQ1 and to genetic knockdown of BET proteins.

Further investigation revealed that resistance to BET inhibitors emerges from LSCs, both ex vivo and in vivo. And that resistance is, in part, a result of increased Wnt/β-catenin signaling.

The researchers noted that not all LSCs are intrinsically resistant to BET inhibition, but a small proportion of them are either transcriptionally primed or display rapid transcriptional plasticity to survive the initial BET inhibitor challenge. The team said these cells then thrive and become the dominant population.

These findings are consistent with results of the other study, conducted by Johannes Zuber, MD, of the Research Institute of Molecular Pathology in Vienna, Austria, and his colleagues.

With this study, the researchers set out to determine why only certain leukemia subtypes are sensitive to BET inhibitors. Their experiments revealed that loss of the PRC2 complex, which is known to inactivate genes during normal development, can render leukemia cells resistant to BET inhibitors.

By further characterizing these resistant cells, the team found that MYC and other BRD4-regulated genes (which are turned off by BET inhibitors) were back on again. So the leukemia cells had found a way to activate these genes in the absence of BRD4.

The researchers then compared leukemia cells that had acquired resistance during BET inhibitor treatment to leukemia cells that were resistant in the first place.

In both cases, the cells used similar pathways to turn critical genes such as MYC back on and thereby escape the effects of BET inhibition. A pathway that proved particularly important was the Wnt signaling pathway, which is known to activate MYC in cancers.

To determine whether this knowledge could be used to predict which patients will respond to BET inhibitors, the researchers measured Wnt signaling markers in samples from leukemia patients.

The team found that cells with low Wnt activity were sensitive to BET inhibitors, while high Wnt activity was associated with resistance.

Specifically, the researchers quantified 9 Wnt-associated transcripts in sensitive and resistant samples. Three of these transcripts—TCF4, CCND2, and HOXB4—were significantly overexpressed in resistant samples.

So the team used these 3 transcripts to establish a “resistance index” that, they believe, may provide a first step toward developing a predictive biomarker.

The researchers said, collectively, their study reveals that leukemia cells can become resistant to BET inhibitors by rewiring the regulation of critical BRD4 target genes. This transcriptional plasticity highlights an emerging mode of drug resistance that is distinct from established resistance mechanisms such as mutations in binding pockets or drug elimination through efflux pumps.

Dr Zuber and his colleagues believe that a better understanding of these adaptation mechanisms will lead to combination therapies that will ultimately “outsmart” cancer cells.

“We now have learned that cancer cells can adapt to targeted therapies, but their repertoire of escape routes is quite limited,” Dr Zuber said. “A better understanding of the common escape routes will allow us to predict the next effective targeted therapy so that we are always one step ahead of the cancer cell.”

Slide showing LSCs

Image by Robert Paulson

Two groups of researchers have reported results that help explain how leukemia resists treatment with BET inhibitors.

One group was able to grow and maintain leukemia stem cells (LSCs) in vitro, and their subsequent experiments showed how LSCs react to BET inhibition.

The other group found evidence to suggest that by measuring Wnt signaling markers, we might be able to predict which patients will respond to BET inhibition.

Both groups described their research in letters to Nature.

“[T]he risk of resistance developing is common in any cancer treatment,” said Mark Dawson, PhD, a researcher at Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia and an author of the LSC study.

“Knowing precisely how that happens in advance puts us one step ahead in outmaneuvering the disease. Being able to grow and maintain leukemia

stem cells in vitro also gives us unprecedented access and insight into how they work so we can find new and better ways to target and destroy them.”

In their study, Dr Dawson and his colleagues assessed BET inhibitor resistance in a model of acute myeloid leukemia.

The team transduced murine hematopoietic stem and progenitor cells with MLL–AF9 and treated the cells with the BET inhibitor I-BET or dimethylsulfoxide (vehicle). They then isolated individual blast colonies to generate 4 vehicle-treated and 5 I-BET-resistant cell lines.

The researchers found that resistance to I-BET also conferred resistance to the chemically distinct BET inhibitor JQ1 and to genetic knockdown of BET proteins.

Further investigation revealed that resistance to BET inhibitors emerges from LSCs, both ex vivo and in vivo. And that resistance is, in part, a result of increased Wnt/β-catenin signaling.

The researchers noted that not all LSCs are intrinsically resistant to BET inhibition, but a small proportion of them are either transcriptionally primed or display rapid transcriptional plasticity to survive the initial BET inhibitor challenge. The team said these cells then thrive and become the dominant population.

These findings are consistent with results of the other study, conducted by Johannes Zuber, MD, of the Research Institute of Molecular Pathology in Vienna, Austria, and his colleagues.

With this study, the researchers set out to determine why only certain leukemia subtypes are sensitive to BET inhibitors. Their experiments revealed that loss of the PRC2 complex, which is known to inactivate genes during normal development, can render leukemia cells resistant to BET inhibitors.

By further characterizing these resistant cells, the team found that MYC and other BRD4-regulated genes (which are turned off by BET inhibitors) were back on again. So the leukemia cells had found a way to activate these genes in the absence of BRD4.

The researchers then compared leukemia cells that had acquired resistance during BET inhibitor treatment to leukemia cells that were resistant in the first place.

In both cases, the cells used similar pathways to turn critical genes such as MYC back on and thereby escape the effects of BET inhibition. A pathway that proved particularly important was the Wnt signaling pathway, which is known to activate MYC in cancers.

To determine whether this knowledge could be used to predict which patients will respond to BET inhibitors, the researchers measured Wnt signaling markers in samples from leukemia patients.

The team found that cells with low Wnt activity were sensitive to BET inhibitors, while high Wnt activity was associated with resistance.

Specifically, the researchers quantified 9 Wnt-associated transcripts in sensitive and resistant samples. Three of these transcripts—TCF4, CCND2, and HOXB4—were significantly overexpressed in resistant samples.

So the team used these 3 transcripts to establish a “resistance index” that, they believe, may provide a first step toward developing a predictive biomarker.

The researchers said, collectively, their study reveals that leukemia cells can become resistant to BET inhibitors by rewiring the regulation of critical BRD4 target genes. This transcriptional plasticity highlights an emerging mode of drug resistance that is distinct from established resistance mechanisms such as mutations in binding pockets or drug elimination through efflux pumps.

Dr Zuber and his colleagues believe that a better understanding of these adaptation mechanisms will lead to combination therapies that will ultimately “outsmart” cancer cells.

“We now have learned that cancer cells can adapt to targeted therapies, but their repertoire of escape routes is quite limited,” Dr Zuber said. “A better understanding of the common escape routes will allow us to predict the next effective targeted therapy so that we are always one step ahead of the cancer cell.”

Slide showing LSCs

Image by Robert Paulson

Two groups of researchers have reported results that help explain how leukemia resists treatment with BET inhibitors.

One group was able to grow and maintain leukemia stem cells (LSCs) in vitro, and their subsequent experiments showed how LSCs react to BET inhibition.

The other group found evidence to suggest that by measuring Wnt signaling markers, we might be able to predict which patients will respond to BET inhibition.

Both groups described their research in letters to Nature.

“[T]he risk of resistance developing is common in any cancer treatment,” said Mark Dawson, PhD, a researcher at Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia and an author of the LSC study.

“Knowing precisely how that happens in advance puts us one step ahead in outmaneuvering the disease. Being able to grow and maintain leukemia

stem cells in vitro also gives us unprecedented access and insight into how they work so we can find new and better ways to target and destroy them.”

In their study, Dr Dawson and his colleagues assessed BET inhibitor resistance in a model of acute myeloid leukemia.

The team transduced murine hematopoietic stem and progenitor cells with MLL–AF9 and treated the cells with the BET inhibitor I-BET or dimethylsulfoxide (vehicle). They then isolated individual blast colonies to generate 4 vehicle-treated and 5 I-BET-resistant cell lines.

The researchers found that resistance to I-BET also conferred resistance to the chemically distinct BET inhibitor JQ1 and to genetic knockdown of BET proteins.

Further investigation revealed that resistance to BET inhibitors emerges from LSCs, both ex vivo and in vivo. And that resistance is, in part, a result of increased Wnt/β-catenin signaling.

The researchers noted that not all LSCs are intrinsically resistant to BET inhibition, but a small proportion of them are either transcriptionally primed or display rapid transcriptional plasticity to survive the initial BET inhibitor challenge. The team said these cells then thrive and become the dominant population.

These findings are consistent with results of the other study, conducted by Johannes Zuber, MD, of the Research Institute of Molecular Pathology in Vienna, Austria, and his colleagues.

With this study, the researchers set out to determine why only certain leukemia subtypes are sensitive to BET inhibitors. Their experiments revealed that loss of the PRC2 complex, which is known to inactivate genes during normal development, can render leukemia cells resistant to BET inhibitors.

By further characterizing these resistant cells, the team found that MYC and other BRD4-regulated genes (which are turned off by BET inhibitors) were back on again. So the leukemia cells had found a way to activate these genes in the absence of BRD4.

The researchers then compared leukemia cells that had acquired resistance during BET inhibitor treatment to leukemia cells that were resistant in the first place.

In both cases, the cells used similar pathways to turn critical genes such as MYC back on and thereby escape the effects of BET inhibition. A pathway that proved particularly important was the Wnt signaling pathway, which is known to activate MYC in cancers.

To determine whether this knowledge could be used to predict which patients will respond to BET inhibitors, the researchers measured Wnt signaling markers in samples from leukemia patients.

The team found that cells with low Wnt activity were sensitive to BET inhibitors, while high Wnt activity was associated with resistance.

Specifically, the researchers quantified 9 Wnt-associated transcripts in sensitive and resistant samples. Three of these transcripts—TCF4, CCND2, and HOXB4—were significantly overexpressed in resistant samples.

So the team used these 3 transcripts to establish a “resistance index” that, they believe, may provide a first step toward developing a predictive biomarker.

The researchers said, collectively, their study reveals that leukemia cells can become resistant to BET inhibitors by rewiring the regulation of critical BRD4 target genes. This transcriptional plasticity highlights an emerging mode of drug resistance that is distinct from established resistance mechanisms such as mutations in binding pockets or drug elimination through efflux pumps.

Dr Zuber and his colleagues believe that a better understanding of these adaptation mechanisms will lead to combination therapies that will ultimately “outsmart” cancer cells.

“We now have learned that cancer cells can adapt to targeted therapies, but their repertoire of escape routes is quite limited,” Dr Zuber said. “A better understanding of the common escape routes will allow us to predict the next effective targeted therapy so that we are always one step ahead of the cancer cell.”

Withania somnifera

The active compound in a plant extract has shown promise for treating non-Hodgkin lymphomas (NHLs), according to researchers.

The compound, withaferin A, is a steroidal lactone isolated from the Ayruvedic medicinal plant Ashwagandha (Withania somnifera).

Withaferin A has previously exhibited activity against a range of solid tumor malignancies, but its effects in NHLs and other hematologic malignancies have not been well-studied.

So Subbarao Bondada, PhD, of the University of Kentucky in Lexington, and his colleagues tested withaferin A in NHLs and reported their results in Cancer Biology and Therapy.

Withaferin A exhibited activity in several human B-cell lymphoma cell lines—the diffuse large B-cell lymphoma (DLBCL) cell lines LY-3, LY-10, and SudHL-6; the Burkitt lymphoma cell lines Raji and Ramos; and the mantle cell lymphoma cell line MINO.

Ramos was the most sensitive to withaferin A, and the mantle cell lymphoma cell line JEKO was the most resistant. The researchers said they are still investigating this resistance.

Withaferin A also inhibited the growth of the murine immature B-cell lymphoma cell line BKS-2 and the germinal center lymphoma cell line A20-Luc/YFP.

Further investigation revealed that withaferin A induces cell-cycle arrest, prompts apoptosis, inhibits NF-kB nuclear translocation, and reduces the expression of pro-survival signals in B-cell lymphomas.

The researchers also found evidence to suggest that withaferin A inhibits the activity of Hsp90. Although Hsp90 levels were unaltered in withaferin-A-treated lymphoma cells, the team observed a “robust” increase in Hsp70 expression levels (which suggests a decrease in Hsp90 function).

Finally, the researchers tested withaferin A in mice injected with the murine DLBCL line A20-Luc. The treatment proved active against A20-Luc cells but did not affect other proliferating cells.

Mice treated with withaferin A had a significant reduction in tumor size, compared to placebo-treated mice, on days 10 and 13 (P<0.05).

Based on these results, the researchers concluded that withaferin A may hold promise for treating NHL, particularly DLBCL.

“It may be possible to develop orally administered versions of withaferin A that could be used in lymphoma patients with fewer side effects than current chemotherapy regimens,” Dr Bondada said.

He and his colleagues are now testing withaferin A in chronic lymphocytic leukemia.

Withania somnifera

The active compound in a plant extract has shown promise for treating non-Hodgkin lymphomas (NHLs), according to researchers.

The compound, withaferin A, is a steroidal lactone isolated from the Ayruvedic medicinal plant Ashwagandha (Withania somnifera).

Withaferin A has previously exhibited activity against a range of solid tumor malignancies, but its effects in NHLs and other hematologic malignancies have not been well-studied.

So Subbarao Bondada, PhD, of the University of Kentucky in Lexington, and his colleagues tested withaferin A in NHLs and reported their results in Cancer Biology and Therapy.

Withaferin A exhibited activity in several human B-cell lymphoma cell lines—the diffuse large B-cell lymphoma (DLBCL) cell lines LY-3, LY-10, and SudHL-6; the Burkitt lymphoma cell lines Raji and Ramos; and the mantle cell lymphoma cell line MINO.

Ramos was the most sensitive to withaferin A, and the mantle cell lymphoma cell line JEKO was the most resistant. The researchers said they are still investigating this resistance.

Withaferin A also inhibited the growth of the murine immature B-cell lymphoma cell line BKS-2 and the germinal center lymphoma cell line A20-Luc/YFP.

Further investigation revealed that withaferin A induces cell-cycle arrest, prompts apoptosis, inhibits NF-kB nuclear translocation, and reduces the expression of pro-survival signals in B-cell lymphomas.

The researchers also found evidence to suggest that withaferin A inhibits the activity of Hsp90. Although Hsp90 levels were unaltered in withaferin-A-treated lymphoma cells, the team observed a “robust” increase in Hsp70 expression levels (which suggests a decrease in Hsp90 function).

Finally, the researchers tested withaferin A in mice injected with the murine DLBCL line A20-Luc. The treatment proved active against A20-Luc cells but did not affect other proliferating cells.

Mice treated with withaferin A had a significant reduction in tumor size, compared to placebo-treated mice, on days 10 and 13 (P<0.05).

Based on these results, the researchers concluded that withaferin A may hold promise for treating NHL, particularly DLBCL.

“It may be possible to develop orally administered versions of withaferin A that could be used in lymphoma patients with fewer side effects than current chemotherapy regimens,” Dr Bondada said.

He and his colleagues are now testing withaferin A in chronic lymphocytic leukemia.

Withania somnifera

The active compound in a plant extract has shown promise for treating non-Hodgkin lymphomas (NHLs), according to researchers.

The compound, withaferin A, is a steroidal lactone isolated from the Ayruvedic medicinal plant Ashwagandha (Withania somnifera).

Withaferin A has previously exhibited activity against a range of solid tumor malignancies, but its effects in NHLs and other hematologic malignancies have not been well-studied.

So Subbarao Bondada, PhD, of the University of Kentucky in Lexington, and his colleagues tested withaferin A in NHLs and reported their results in Cancer Biology and Therapy.

Withaferin A exhibited activity in several human B-cell lymphoma cell lines—the diffuse large B-cell lymphoma (DLBCL) cell lines LY-3, LY-10, and SudHL-6; the Burkitt lymphoma cell lines Raji and Ramos; and the mantle cell lymphoma cell line MINO.

Ramos was the most sensitive to withaferin A, and the mantle cell lymphoma cell line JEKO was the most resistant. The researchers said they are still investigating this resistance.

Withaferin A also inhibited the growth of the murine immature B-cell lymphoma cell line BKS-2 and the germinal center lymphoma cell line A20-Luc/YFP.

Further investigation revealed that withaferin A induces cell-cycle arrest, prompts apoptosis, inhibits NF-kB nuclear translocation, and reduces the expression of pro-survival signals in B-cell lymphomas.

The researchers also found evidence to suggest that withaferin A inhibits the activity of Hsp90. Although Hsp90 levels were unaltered in withaferin-A-treated lymphoma cells, the team observed a “robust” increase in Hsp70 expression levels (which suggests a decrease in Hsp90 function).

Finally, the researchers tested withaferin A in mice injected with the murine DLBCL line A20-Luc. The treatment proved active against A20-Luc cells but did not affect other proliferating cells.

Mice treated with withaferin A had a significant reduction in tumor size, compared to placebo-treated mice, on days 10 and 13 (P<0.05).

Based on these results, the researchers concluded that withaferin A may hold promise for treating NHL, particularly DLBCL.

“It may be possible to develop orally administered versions of withaferin A that could be used in lymphoma patients with fewer side effects than current chemotherapy regimens,” Dr Bondada said.

He and his colleagues are now testing withaferin A in chronic lymphocytic leukemia.

Researcher in the lab

Photo by Bill Branson

Scientists say they have developed a tool that can guide the allocation of resources for biomedical research in an unbiased way.

The tool, called the Research Opportunity Index (ROI), measures disparities between resources dedicated to a disease and its relative burden on society.

This reveals diseases that receive a disproportionate share of resources and opportunities for high-impact investment or the realignment of existing resources.

The ROI was designed to provide an unbiased, data-driven framework to help scientific and political communities assess resource investment and identify unmet medical needs.

The tool is described in a letter to Nature Biotechnology.

“The misalignment of resources in biomedical research could be likened to poor budgeting of household finances,” said Andrey Rzhetsky, PhD, of the University of Chicago in Illinois.

“It would be bad to spend all your money on food, for example, and have nothing for rent. Resources are finite, and attention to each problem, ideally, should be proportional to the need.”

With this in mind, Dr Rzhetsky and his colleagues created the ROI. They used it to estimate the societal burden of 1400 medical conditions in the US over a 12-year timespan, based on frequency of diagnosis and healthcare insurance costs, as well as research publications, awarded grants, and clinical trials for each condition.

The tool revealed misalignments, which allowed the scientists to create an “investment portfolio” of the resources dedicated to each disease, relative to its burden on the US healthcare system.

The team found that breast cancer, for example, stands out as a disease with higher dedicated resources than its relative societal burden. On the opposite end of the spectrum, Hashimoto’s thyroiditis is among the conditions with the most investment potential.

While Hashimoto’s disease has nearly the same incidence among women as breast cancer, there were only 16 open clinical trials for Hashimoto’s disease as of August 2015, according to a list on clinicaltrials.gov. Breast cancer had 2205 open trials.

Dr Rzhetsky and his colleagues acknowledge that the question of what makes a condition more deserving of funding than any other ailment is complex and multifaceted. But the team hopes this new tool can aid decisions on how best to allocate funds and other resources.

By providing a framework based on unbiased quantitative analytics and big data, they hope to identify diseases that are high-impact and rewarding targets for additional investment.

“Some diseases stick in the public’s attention,” Dr Rzhetsky said. “We have a distorted map of the frequency and importance of events from media and articles, and, without special efforts to reconcile the reality, we are inherently biased.”

The team is now working to incorporate other models of funding distribution into their tool to account for additional variables.

For example, the “trendy model,” which supports investment for diseases with large emotional impact, suggests that even though this reduces funding for other diseases, there may still be benefits as basic science discoveries are added to the scientific and medical community.

Researcher in the lab

Photo by Bill Branson

Scientists say they have developed a tool that can guide the allocation of resources for biomedical research in an unbiased way.

The tool, called the Research Opportunity Index (ROI), measures disparities between resources dedicated to a disease and its relative burden on society.

This reveals diseases that receive a disproportionate share of resources and opportunities for high-impact investment or the realignment of existing resources.

The ROI was designed to provide an unbiased, data-driven framework to help scientific and political communities assess resource investment and identify unmet medical needs.

The tool is described in a letter to Nature Biotechnology.

“The misalignment of resources in biomedical research could be likened to poor budgeting of household finances,” said Andrey Rzhetsky, PhD, of the University of Chicago in Illinois.

“It would be bad to spend all your money on food, for example, and have nothing for rent. Resources are finite, and attention to each problem, ideally, should be proportional to the need.”

With this in mind, Dr Rzhetsky and his colleagues created the ROI. They used it to estimate the societal burden of 1400 medical conditions in the US over a 12-year timespan, based on frequency of diagnosis and healthcare insurance costs, as well as research publications, awarded grants, and clinical trials for each condition.

The tool revealed misalignments, which allowed the scientists to create an “investment portfolio” of the resources dedicated to each disease, relative to its burden on the US healthcare system.

The team found that breast cancer, for example, stands out as a disease with higher dedicated resources than its relative societal burden. On the opposite end of the spectrum, Hashimoto’s thyroiditis is among the conditions with the most investment potential.

While Hashimoto’s disease has nearly the same incidence among women as breast cancer, there were only 16 open clinical trials for Hashimoto’s disease as of August 2015, according to a list on clinicaltrials.gov. Breast cancer had 2205 open trials.

Dr Rzhetsky and his colleagues acknowledge that the question of what makes a condition more deserving of funding than any other ailment is complex and multifaceted. But the team hopes this new tool can aid decisions on how best to allocate funds and other resources.

By providing a framework based on unbiased quantitative analytics and big data, they hope to identify diseases that are high-impact and rewarding targets for additional investment.

“Some diseases stick in the public’s attention,” Dr Rzhetsky said. “We have a distorted map of the frequency and importance of events from media and articles, and, without special efforts to reconcile the reality, we are inherently biased.”

The team is now working to incorporate other models of funding distribution into their tool to account for additional variables.

For example, the “trendy model,” which supports investment for diseases with large emotional impact, suggests that even though this reduces funding for other diseases, there may still be benefits as basic science discoveries are added to the scientific and medical community.

Researcher in the lab

Photo by Bill Branson

Scientists say they have developed a tool that can guide the allocation of resources for biomedical research in an unbiased way.

The tool, called the Research Opportunity Index (ROI), measures disparities between resources dedicated to a disease and its relative burden on society.

This reveals diseases that receive a disproportionate share of resources and opportunities for high-impact investment or the realignment of existing resources.

The ROI was designed to provide an unbiased, data-driven framework to help scientific and political communities assess resource investment and identify unmet medical needs.

The tool is described in a letter to Nature Biotechnology.

“The misalignment of resources in biomedical research could be likened to poor budgeting of household finances,” said Andrey Rzhetsky, PhD, of the University of Chicago in Illinois.

“It would be bad to spend all your money on food, for example, and have nothing for rent. Resources are finite, and attention to each problem, ideally, should be proportional to the need.”

With this in mind, Dr Rzhetsky and his colleagues created the ROI. They used it to estimate the societal burden of 1400 medical conditions in the US over a 12-year timespan, based on frequency of diagnosis and healthcare insurance costs, as well as research publications, awarded grants, and clinical trials for each condition.

The tool revealed misalignments, which allowed the scientists to create an “investment portfolio” of the resources dedicated to each disease, relative to its burden on the US healthcare system.

The team found that breast cancer, for example, stands out as a disease with higher dedicated resources than its relative societal burden. On the opposite end of the spectrum, Hashimoto’s thyroiditis is among the conditions with the most investment potential.

While Hashimoto’s disease has nearly the same incidence among women as breast cancer, there were only 16 open clinical trials for Hashimoto’s disease as of August 2015, according to a list on clinicaltrials.gov. Breast cancer had 2205 open trials.

Dr Rzhetsky and his colleagues acknowledge that the question of what makes a condition more deserving of funding than any other ailment is complex and multifaceted. But the team hopes this new tool can aid decisions on how best to allocate funds and other resources.

By providing a framework based on unbiased quantitative analytics and big data, they hope to identify diseases that are high-impact and rewarding targets for additional investment.

“Some diseases stick in the public’s attention,” Dr Rzhetsky said. “We have a distorted map of the frequency and importance of events from media and articles, and, without special efforts to reconcile the reality, we are inherently biased.”

The team is now working to incorporate other models of funding distribution into their tool to account for additional variables.

For example, the “trendy model,” which supports investment for diseases with large emotional impact, suggests that even though this reduces funding for other diseases, there may still be benefits as basic science discoveries are added to the scientific and medical community.

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at pdnews@frontlinemedcom.com.

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at pdnews@frontlinemedcom.com.

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at pdnews@frontlinemedcom.com.