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ASVAL Can Save Refluxing Saphenous Veins
Ambulatory selective varicose vein ablation under local anesthesia (ASVAL) can abolish reflux while preserving the great saphenous vein, and benefits can last at least a decade, said Dr. Silvain Chastanet, who helped create the technique and will discuss it Thursday morning.
Historically, a refluxing great saphenous vein was treated by removing it. The ASVAL method preserves the vein by using microphlebotomy to instead remove the varicose reservoir, said Dr. Chastanet of the Riviera Vein Institute in Monaco. “Because each patient is different, this strategy offers tailored, à la carte treatment, as opposed to systematic ablation,” he said. “Doing precise and thorough microphlebectomies is not as simple as one might think, but we will share tips and tricks for performing saphenous sparing venous surgery in an easy and elegant way.”
The ASVAL technique is based on the premise that reflux usually ascends from the tributaries toward the saphenous trunk, rather than following the opposite path, said Dr. Chastanet. Although the ascending pattern is not universal, increasing evidence suggests that it is most common. For example, a study of more than 700 consecutive patients with chronic venous disease showed that patients of CEAP category C4-C6 had significantly greater involvement of the saphenofemoral junction and saphenopopliteal trunk than patients with less advanced venous disease. The authors concluded that reflux usually ascends up from the tributaries and accessory saphenous veins (J Vasc Surg. 2010;51(1):96-103).
Thus, when evaluating a patient with saphenous reflux, surgeons should always ask whether they can spare the great saphenous vein, Dr. Chastanet said. Evidence indicates that if the patient is classified as C2 (varicose veins) and the great saphenous vein is dilated less than 10 mm, ASVAL may be a valid option, especially if reflux is localized above the knee, with the varices localized to the thigh.
Techniques such as ASVAL are a major advance, but questions persist about surgically treating varicose disease, Dr. Chastanet noted. For example, although ascending disease appears to be most common, it can convert to descending disease or patients can have a refluxing saphenous trunk without tributaries. “We still do not know which patients are likely to have descending or ascending disease, and why,” Dr. Chastanet said. Likewise, experts continue to debate whether phlebectomy should be performed together with saphenous ablation. “Considering that some varicosities will disappear after endothermal ablation of the saphenous vein, some surgeons consider concomitant phlebectomy to be overtreatment,” Dr. Chastenet noted. “Conversely, if we consider that the disease begins at the tributary level according to the ascending theory, it seems obvious to focus treatment on the varicose tributaries, which are the main concern for the majority of patients.”
Bringing techniques such as ASVAL into community practice involves practical challenges, too. Microphlebectomy is “clearly” the best cosmetic option, but is not taught during surgical or phlebology training, Dr. Chastanet said. “There is a need to develop new tools for treating the varicose tributaries in an easier and faster way.” Such advances could help transition procedures such as ASVAL to outpatient settings, which is not now the norm in most countries, he noted. “Using local anesthesia, mini-invasive surgical procedures with immediate ambulation will enable us to reach this goal.”
Session 63
“Venous Clinical Examination and Hemodynamics”
Thursday 8:13 a.m. – 8:18 a.m.
Trianon Ballroom, 3rd Floor
Ambulatory selective varicose vein ablation under local anesthesia (ASVAL) can abolish reflux while preserving the great saphenous vein, and benefits can last at least a decade, said Dr. Silvain Chastanet, who helped create the technique and will discuss it Thursday morning.
Historically, a refluxing great saphenous vein was treated by removing it. The ASVAL method preserves the vein by using microphlebotomy to instead remove the varicose reservoir, said Dr. Chastanet of the Riviera Vein Institute in Monaco. “Because each patient is different, this strategy offers tailored, à la carte treatment, as opposed to systematic ablation,” he said. “Doing precise and thorough microphlebectomies is not as simple as one might think, but we will share tips and tricks for performing saphenous sparing venous surgery in an easy and elegant way.”
The ASVAL technique is based on the premise that reflux usually ascends from the tributaries toward the saphenous trunk, rather than following the opposite path, said Dr. Chastanet. Although the ascending pattern is not universal, increasing evidence suggests that it is most common. For example, a study of more than 700 consecutive patients with chronic venous disease showed that patients of CEAP category C4-C6 had significantly greater involvement of the saphenofemoral junction and saphenopopliteal trunk than patients with less advanced venous disease. The authors concluded that reflux usually ascends up from the tributaries and accessory saphenous veins (J Vasc Surg. 2010;51(1):96-103).
Thus, when evaluating a patient with saphenous reflux, surgeons should always ask whether they can spare the great saphenous vein, Dr. Chastanet said. Evidence indicates that if the patient is classified as C2 (varicose veins) and the great saphenous vein is dilated less than 10 mm, ASVAL may be a valid option, especially if reflux is localized above the knee, with the varices localized to the thigh.
Techniques such as ASVAL are a major advance, but questions persist about surgically treating varicose disease, Dr. Chastanet noted. For example, although ascending disease appears to be most common, it can convert to descending disease or patients can have a refluxing saphenous trunk without tributaries. “We still do not know which patients are likely to have descending or ascending disease, and why,” Dr. Chastanet said. Likewise, experts continue to debate whether phlebectomy should be performed together with saphenous ablation. “Considering that some varicosities will disappear after endothermal ablation of the saphenous vein, some surgeons consider concomitant phlebectomy to be overtreatment,” Dr. Chastenet noted. “Conversely, if we consider that the disease begins at the tributary level according to the ascending theory, it seems obvious to focus treatment on the varicose tributaries, which are the main concern for the majority of patients.”
Bringing techniques such as ASVAL into community practice involves practical challenges, too. Microphlebectomy is “clearly” the best cosmetic option, but is not taught during surgical or phlebology training, Dr. Chastanet said. “There is a need to develop new tools for treating the varicose tributaries in an easier and faster way.” Such advances could help transition procedures such as ASVAL to outpatient settings, which is not now the norm in most countries, he noted. “Using local anesthesia, mini-invasive surgical procedures with immediate ambulation will enable us to reach this goal.”
Session 63
“Venous Clinical Examination and Hemodynamics”
Thursday 8:13 a.m. – 8:18 a.m.
Trianon Ballroom, 3rd Floor
Ambulatory selective varicose vein ablation under local anesthesia (ASVAL) can abolish reflux while preserving the great saphenous vein, and benefits can last at least a decade, said Dr. Silvain Chastanet, who helped create the technique and will discuss it Thursday morning.
Historically, a refluxing great saphenous vein was treated by removing it. The ASVAL method preserves the vein by using microphlebotomy to instead remove the varicose reservoir, said Dr. Chastanet of the Riviera Vein Institute in Monaco. “Because each patient is different, this strategy offers tailored, à la carte treatment, as opposed to systematic ablation,” he said. “Doing precise and thorough microphlebectomies is not as simple as one might think, but we will share tips and tricks for performing saphenous sparing venous surgery in an easy and elegant way.”
The ASVAL technique is based on the premise that reflux usually ascends from the tributaries toward the saphenous trunk, rather than following the opposite path, said Dr. Chastanet. Although the ascending pattern is not universal, increasing evidence suggests that it is most common. For example, a study of more than 700 consecutive patients with chronic venous disease showed that patients of CEAP category C4-C6 had significantly greater involvement of the saphenofemoral junction and saphenopopliteal trunk than patients with less advanced venous disease. The authors concluded that reflux usually ascends up from the tributaries and accessory saphenous veins (J Vasc Surg. 2010;51(1):96-103).
Thus, when evaluating a patient with saphenous reflux, surgeons should always ask whether they can spare the great saphenous vein, Dr. Chastanet said. Evidence indicates that if the patient is classified as C2 (varicose veins) and the great saphenous vein is dilated less than 10 mm, ASVAL may be a valid option, especially if reflux is localized above the knee, with the varices localized to the thigh.
Techniques such as ASVAL are a major advance, but questions persist about surgically treating varicose disease, Dr. Chastanet noted. For example, although ascending disease appears to be most common, it can convert to descending disease or patients can have a refluxing saphenous trunk without tributaries. “We still do not know which patients are likely to have descending or ascending disease, and why,” Dr. Chastanet said. Likewise, experts continue to debate whether phlebectomy should be performed together with saphenous ablation. “Considering that some varicosities will disappear after endothermal ablation of the saphenous vein, some surgeons consider concomitant phlebectomy to be overtreatment,” Dr. Chastenet noted. “Conversely, if we consider that the disease begins at the tributary level according to the ascending theory, it seems obvious to focus treatment on the varicose tributaries, which are the main concern for the majority of patients.”
Bringing techniques such as ASVAL into community practice involves practical challenges, too. Microphlebectomy is “clearly” the best cosmetic option, but is not taught during surgical or phlebology training, Dr. Chastanet said. “There is a need to develop new tools for treating the varicose tributaries in an easier and faster way.” Such advances could help transition procedures such as ASVAL to outpatient settings, which is not now the norm in most countries, he noted. “Using local anesthesia, mini-invasive surgical procedures with immediate ambulation will enable us to reach this goal.”
Session 63
“Venous Clinical Examination and Hemodynamics”
Thursday 8:13 a.m. – 8:18 a.m.
Trianon Ballroom, 3rd Floor
Sunscreen and Sperm: Can Chemical UV Filters Alter Sperm Function?
In an article published online on September 1 in Endocrinology, Rehfeld et al discussed their results after testing 29 UV filters. They found that 13 of 29 filters tested had in vitro effects on Ca2+: 4-methylbenzylidene camphor, 3-benzylidene camphor, menthyl anthranilate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, benzylidene camphor sulfonic acid, homosalate, ethylhexyl methoxycinnamate, octcrylene, butyl methoxydibenzoylmethane, and diethylamino hydroxybenzoyl hexyl benzoate.
This study was prompted by a prior study by Schiffer et al (EMBO Rep. 2014;15:758-765) on multiple endocrine disrupting chemicals of which 33 of 96 tested chemicals induced Ca2+ signals in human sperm cells in vitro. Of these previously tested chemicals, some of the chemical sunscreen filters were the most potent, leading to the current study.
Rehfeld et al sought to determine how the UV filters affected calcium signaling, which is a pathway that is essential for sperm cells to be able to swim healthily. These calcium-signaling pathways usually are triggered by progesterone, but the authors showed that 13 of 29 UV filters (45%) also commenced calcium signaling. This effect began at low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens.
What’s the issue?
Are these chemical UV filters mimicking progesterone in vivo and could it be interfering with sperm motility? A suboptimal progesterone-induced Ca2+ influx has been associated with reduced male fertility and CatSper (cation channel of sperm) is essential for male fertility (Hum Reprod. 1995;10:120-124).
The UV filters tested are widely available in Europe and the United States. Although this study was in vitro, the in vivo effects will need to be explored. It has been reported by Chivsvert et al (Anal Chim Acta. 2012;752:11-29) that some UV filters can be transcutaneously absorbed into bodily tissues, which could be potentially important for men trying to conceive or for reproductively challenged couples.
What do you discuss with your patients regarding sunscreen safety?
In an article published online on September 1 in Endocrinology, Rehfeld et al discussed their results after testing 29 UV filters. They found that 13 of 29 filters tested had in vitro effects on Ca2+: 4-methylbenzylidene camphor, 3-benzylidene camphor, menthyl anthranilate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, benzylidene camphor sulfonic acid, homosalate, ethylhexyl methoxycinnamate, octcrylene, butyl methoxydibenzoylmethane, and diethylamino hydroxybenzoyl hexyl benzoate.
This study was prompted by a prior study by Schiffer et al (EMBO Rep. 2014;15:758-765) on multiple endocrine disrupting chemicals of which 33 of 96 tested chemicals induced Ca2+ signals in human sperm cells in vitro. Of these previously tested chemicals, some of the chemical sunscreen filters were the most potent, leading to the current study.
Rehfeld et al sought to determine how the UV filters affected calcium signaling, which is a pathway that is essential for sperm cells to be able to swim healthily. These calcium-signaling pathways usually are triggered by progesterone, but the authors showed that 13 of 29 UV filters (45%) also commenced calcium signaling. This effect began at low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens.
What’s the issue?
Are these chemical UV filters mimicking progesterone in vivo and could it be interfering with sperm motility? A suboptimal progesterone-induced Ca2+ influx has been associated with reduced male fertility and CatSper (cation channel of sperm) is essential for male fertility (Hum Reprod. 1995;10:120-124).
The UV filters tested are widely available in Europe and the United States. Although this study was in vitro, the in vivo effects will need to be explored. It has been reported by Chivsvert et al (Anal Chim Acta. 2012;752:11-29) that some UV filters can be transcutaneously absorbed into bodily tissues, which could be potentially important for men trying to conceive or for reproductively challenged couples.
What do you discuss with your patients regarding sunscreen safety?
In an article published online on September 1 in Endocrinology, Rehfeld et al discussed their results after testing 29 UV filters. They found that 13 of 29 filters tested had in vitro effects on Ca2+: 4-methylbenzylidene camphor, 3-benzylidene camphor, menthyl anthranilate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, benzylidene camphor sulfonic acid, homosalate, ethylhexyl methoxycinnamate, octcrylene, butyl methoxydibenzoylmethane, and diethylamino hydroxybenzoyl hexyl benzoate.
This study was prompted by a prior study by Schiffer et al (EMBO Rep. 2014;15:758-765) on multiple endocrine disrupting chemicals of which 33 of 96 tested chemicals induced Ca2+ signals in human sperm cells in vitro. Of these previously tested chemicals, some of the chemical sunscreen filters were the most potent, leading to the current study.
Rehfeld et al sought to determine how the UV filters affected calcium signaling, which is a pathway that is essential for sperm cells to be able to swim healthily. These calcium-signaling pathways usually are triggered by progesterone, but the authors showed that 13 of 29 UV filters (45%) also commenced calcium signaling. This effect began at low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens.
What’s the issue?
Are these chemical UV filters mimicking progesterone in vivo and could it be interfering with sperm motility? A suboptimal progesterone-induced Ca2+ influx has been associated with reduced male fertility and CatSper (cation channel of sperm) is essential for male fertility (Hum Reprod. 1995;10:120-124).
The UV filters tested are widely available in Europe and the United States. Although this study was in vitro, the in vivo effects will need to be explored. It has been reported by Chivsvert et al (Anal Chim Acta. 2012;752:11-29) that some UV filters can be transcutaneously absorbed into bodily tissues, which could be potentially important for men trying to conceive or for reproductively challenged couples.
What do you discuss with your patients regarding sunscreen safety?
Genetically corrected skin grafts explored in dystrophic EB
Genetically corrected autologous skin grafts produced wound healing in a phase I trial involving four men with recessive dystrophic epidermolysis bullosa in what the investigators described as the first human trial of cutaneous gene therapy for this indication, according to a report published in JAMA.
The wound healing varied according to graft site and across the four patients, and generally declined over the course of 1 year of follow-up. Given that this study focused on safety outcomes and that the treatment’s safety profile was deemed “acceptable,” the Food and Drug Administration has permitted a phase IIA trial (NCT01263379) that is currently enrolling adolescents with the disease and will focus on clinical outcomes. Longer-term follow-up of these four patients will continue, and “controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts,” said Zurab Siprashvili, Ph.D., of Stanford (Calif.) University and associates.
The investigators assessed whether grafting of type VII collagen gene-corrected autologous keratinocytes onto existing wounds would promote their healing. They first harvested and cultured keratinocytes from biopsies of the patients’ unwounded, unscarred skin and transduced these samples with COL7A1-containing retrovirus, producing eight gene-corrected grafts for each patient. All the biopsy sites healed completely, without complications.
The wound beds were prepared for engraftment by cauterization to minimize any retained epidermal stem cells. Then grafts were applied using dissolvable sutures to six wound sites on each patient; the sites had been selected for their accessibility, their potential to enhance the patients’ quality of life, and their ability to ease the period of immobilization after grafting.
All 24 grafts were well tolerated, and no serious adverse events occurred during 1 year of follow-up, which represented approximately 10 epidermal turnover cycles. The most common adverse events – pruritus (three patients) and drainage (two patients) at the graft site – were mild. None of the patients showed systemic autoimmune symptoms or increased blistering outside of the grafted areas, and no clinical signs of malignancy developed.
The gene-corrected graft sites showed type VII collagen localization to anchoring fibrils at the dermal-epidermal junction, in contrast to control sites that showed no such localization or fibril formation. “Gene-corrected graft sites showed fully differentiated epidermis with spinous and granular layers, which were positive for epidermal markers keratin 14, keratin 1, and loricirin resembling normal skin,” Dr. Siprashvili and his associates wrote.
At 1-month follow-up, 20 of the 24 grafts showed 75% or greater wound healing, compared with baseline, and the other 4 grafts showed 50%-74% wound healing. At 3 months, 21 of the 24 graft sites showed 75% or greater wound healing while the remaining 3 grafts showed 50%-74% wound healing. At 6 months, 16 of 24 graft sites showed 75% or greater wound healing and 5 graft sites showed 50%-74% wound healing, but 3 graft sites showed extensive blisters or erosions and were considered graft failures. At 12 months, only 12 of the 24 graft sites showed 75% or greater wound healing.
This general decline in efficacy might be related to the relatively small number of stem cells available for transplantation in these patients, who had only small areas of unscarred skin for harvesting. Or it may be that uncorrected cells in the wound beds began competing with corrected cells within the graft and eventually overcame them, the researchers said.
This study was supported by the National Institutes of Health, the Epidermolysis Bullosa Medical Research Foundation, the Epidermolysis Bullosa Research Partnership, and the Palo Alto VA Medical Center. Dr. Siprashvili and some associates reported having U.S. patents pending; two associates also reported ties to Scioderm and Fibrocell.
Genetically corrected autologous skin grafts produced wound healing in a phase I trial involving four men with recessive dystrophic epidermolysis bullosa in what the investigators described as the first human trial of cutaneous gene therapy for this indication, according to a report published in JAMA.
The wound healing varied according to graft site and across the four patients, and generally declined over the course of 1 year of follow-up. Given that this study focused on safety outcomes and that the treatment’s safety profile was deemed “acceptable,” the Food and Drug Administration has permitted a phase IIA trial (NCT01263379) that is currently enrolling adolescents with the disease and will focus on clinical outcomes. Longer-term follow-up of these four patients will continue, and “controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts,” said Zurab Siprashvili, Ph.D., of Stanford (Calif.) University and associates.
The investigators assessed whether grafting of type VII collagen gene-corrected autologous keratinocytes onto existing wounds would promote their healing. They first harvested and cultured keratinocytes from biopsies of the patients’ unwounded, unscarred skin and transduced these samples with COL7A1-containing retrovirus, producing eight gene-corrected grafts for each patient. All the biopsy sites healed completely, without complications.
The wound beds were prepared for engraftment by cauterization to minimize any retained epidermal stem cells. Then grafts were applied using dissolvable sutures to six wound sites on each patient; the sites had been selected for their accessibility, their potential to enhance the patients’ quality of life, and their ability to ease the period of immobilization after grafting.
All 24 grafts were well tolerated, and no serious adverse events occurred during 1 year of follow-up, which represented approximately 10 epidermal turnover cycles. The most common adverse events – pruritus (three patients) and drainage (two patients) at the graft site – were mild. None of the patients showed systemic autoimmune symptoms or increased blistering outside of the grafted areas, and no clinical signs of malignancy developed.
The gene-corrected graft sites showed type VII collagen localization to anchoring fibrils at the dermal-epidermal junction, in contrast to control sites that showed no such localization or fibril formation. “Gene-corrected graft sites showed fully differentiated epidermis with spinous and granular layers, which were positive for epidermal markers keratin 14, keratin 1, and loricirin resembling normal skin,” Dr. Siprashvili and his associates wrote.
At 1-month follow-up, 20 of the 24 grafts showed 75% or greater wound healing, compared with baseline, and the other 4 grafts showed 50%-74% wound healing. At 3 months, 21 of the 24 graft sites showed 75% or greater wound healing while the remaining 3 grafts showed 50%-74% wound healing. At 6 months, 16 of 24 graft sites showed 75% or greater wound healing and 5 graft sites showed 50%-74% wound healing, but 3 graft sites showed extensive blisters or erosions and were considered graft failures. At 12 months, only 12 of the 24 graft sites showed 75% or greater wound healing.
This general decline in efficacy might be related to the relatively small number of stem cells available for transplantation in these patients, who had only small areas of unscarred skin for harvesting. Or it may be that uncorrected cells in the wound beds began competing with corrected cells within the graft and eventually overcame them, the researchers said.
This study was supported by the National Institutes of Health, the Epidermolysis Bullosa Medical Research Foundation, the Epidermolysis Bullosa Research Partnership, and the Palo Alto VA Medical Center. Dr. Siprashvili and some associates reported having U.S. patents pending; two associates also reported ties to Scioderm and Fibrocell.
Genetically corrected autologous skin grafts produced wound healing in a phase I trial involving four men with recessive dystrophic epidermolysis bullosa in what the investigators described as the first human trial of cutaneous gene therapy for this indication, according to a report published in JAMA.
The wound healing varied according to graft site and across the four patients, and generally declined over the course of 1 year of follow-up. Given that this study focused on safety outcomes and that the treatment’s safety profile was deemed “acceptable,” the Food and Drug Administration has permitted a phase IIA trial (NCT01263379) that is currently enrolling adolescents with the disease and will focus on clinical outcomes. Longer-term follow-up of these four patients will continue, and “controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts,” said Zurab Siprashvili, Ph.D., of Stanford (Calif.) University and associates.
The investigators assessed whether grafting of type VII collagen gene-corrected autologous keratinocytes onto existing wounds would promote their healing. They first harvested and cultured keratinocytes from biopsies of the patients’ unwounded, unscarred skin and transduced these samples with COL7A1-containing retrovirus, producing eight gene-corrected grafts for each patient. All the biopsy sites healed completely, without complications.
The wound beds were prepared for engraftment by cauterization to minimize any retained epidermal stem cells. Then grafts were applied using dissolvable sutures to six wound sites on each patient; the sites had been selected for their accessibility, their potential to enhance the patients’ quality of life, and their ability to ease the period of immobilization after grafting.
All 24 grafts were well tolerated, and no serious adverse events occurred during 1 year of follow-up, which represented approximately 10 epidermal turnover cycles. The most common adverse events – pruritus (three patients) and drainage (two patients) at the graft site – were mild. None of the patients showed systemic autoimmune symptoms or increased blistering outside of the grafted areas, and no clinical signs of malignancy developed.
The gene-corrected graft sites showed type VII collagen localization to anchoring fibrils at the dermal-epidermal junction, in contrast to control sites that showed no such localization or fibril formation. “Gene-corrected graft sites showed fully differentiated epidermis with spinous and granular layers, which were positive for epidermal markers keratin 14, keratin 1, and loricirin resembling normal skin,” Dr. Siprashvili and his associates wrote.
At 1-month follow-up, 20 of the 24 grafts showed 75% or greater wound healing, compared with baseline, and the other 4 grafts showed 50%-74% wound healing. At 3 months, 21 of the 24 graft sites showed 75% or greater wound healing while the remaining 3 grafts showed 50%-74% wound healing. At 6 months, 16 of 24 graft sites showed 75% or greater wound healing and 5 graft sites showed 50%-74% wound healing, but 3 graft sites showed extensive blisters or erosions and were considered graft failures. At 12 months, only 12 of the 24 graft sites showed 75% or greater wound healing.
This general decline in efficacy might be related to the relatively small number of stem cells available for transplantation in these patients, who had only small areas of unscarred skin for harvesting. Or it may be that uncorrected cells in the wound beds began competing with corrected cells within the graft and eventually overcame them, the researchers said.
This study was supported by the National Institutes of Health, the Epidermolysis Bullosa Medical Research Foundation, the Epidermolysis Bullosa Research Partnership, and the Palo Alto VA Medical Center. Dr. Siprashvili and some associates reported having U.S. patents pending; two associates also reported ties to Scioderm and Fibrocell.
FROM JAMA
Key clinical point: Genetically corrected autologous skin grafts produced wound healing in a phase I study of four patients with recessive dystrophic epidermolysis bullosa.
Major finding: All 24 grafts were well tolerated, and no serious adverse events occurred during 1 year of follow-up; none of the patients showed systemic autoimmune symptoms or increased blistering outside of the grafted areas, and no clinical signs of malignancy developed.
Data source: A single-center open-label phase I study involving four men followed for 1 year.
Disclosures: This study was supported by the National Institutes of Health, the Epidermolysis Bullosa Medical Research Foundation, the Epidermolysis Bullosa Research Partnership, and the Palo Alto VA Medical Center. Dr. Siprashvili and some associates reported having U.S. patents pending; two associates also reported ties to Scioderm and Fibrocell.
Top 3 things I learned at the NAMS 2016 annual meeting
- Visit NAMS
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Mastoid stimulation significantly reduces episodic migraine frequency
Episodic migraines were safely and effectively treated using percutaneous mastoid electrical stimulators in a randomized, double-blind, sham-controlled, multicenter trial.
Yang Juan of the department of neurology at the Second People’s Hospital of Chengdu (China), and associates reported that a group of 39 migraine patients who received percutaneous mastoid electrical stimulation (PMES) experienced significantly fewer migraine days, compared with a control group of 37 patients who received sham electrical treatment. After 3 months, migraine days were reduced by 71.3% from baseline, compared with a 14.4% reduction in the control group. About a third of PMES patients experienced no migraines in the third month, whereas no patients in the control group had more than a 75% reduction in migraine incidence.
There were no adverse reactions reported either in the PMES group or in the control group during the treatment period.
“The best treatment mode including current intensity and duration is unclear. Whether extension of the time interval (e.g., once or twice a week) of PMES treatment may also have preventive effect remains to be determined. In addition, as the patients recruited in this study were not highly disabled, the preventive effect of PMES treatment in patients with more frequent migraine episodes and in patients with chronic migraine needs further study,” the investigators wrote.
Read the full study in Cephalalgia (2016 Nov 7. doi: 10.1177/0333102416678623).
Episodic migraines were safely and effectively treated using percutaneous mastoid electrical stimulators in a randomized, double-blind, sham-controlled, multicenter trial.
Yang Juan of the department of neurology at the Second People’s Hospital of Chengdu (China), and associates reported that a group of 39 migraine patients who received percutaneous mastoid electrical stimulation (PMES) experienced significantly fewer migraine days, compared with a control group of 37 patients who received sham electrical treatment. After 3 months, migraine days were reduced by 71.3% from baseline, compared with a 14.4% reduction in the control group. About a third of PMES patients experienced no migraines in the third month, whereas no patients in the control group had more than a 75% reduction in migraine incidence.
There were no adverse reactions reported either in the PMES group or in the control group during the treatment period.
“The best treatment mode including current intensity and duration is unclear. Whether extension of the time interval (e.g., once or twice a week) of PMES treatment may also have preventive effect remains to be determined. In addition, as the patients recruited in this study were not highly disabled, the preventive effect of PMES treatment in patients with more frequent migraine episodes and in patients with chronic migraine needs further study,” the investigators wrote.
Read the full study in Cephalalgia (2016 Nov 7. doi: 10.1177/0333102416678623).
Episodic migraines were safely and effectively treated using percutaneous mastoid electrical stimulators in a randomized, double-blind, sham-controlled, multicenter trial.
Yang Juan of the department of neurology at the Second People’s Hospital of Chengdu (China), and associates reported that a group of 39 migraine patients who received percutaneous mastoid electrical stimulation (PMES) experienced significantly fewer migraine days, compared with a control group of 37 patients who received sham electrical treatment. After 3 months, migraine days were reduced by 71.3% from baseline, compared with a 14.4% reduction in the control group. About a third of PMES patients experienced no migraines in the third month, whereas no patients in the control group had more than a 75% reduction in migraine incidence.
There were no adverse reactions reported either in the PMES group or in the control group during the treatment period.
“The best treatment mode including current intensity and duration is unclear. Whether extension of the time interval (e.g., once or twice a week) of PMES treatment may also have preventive effect remains to be determined. In addition, as the patients recruited in this study were not highly disabled, the preventive effect of PMES treatment in patients with more frequent migraine episodes and in patients with chronic migraine needs further study,” the investigators wrote.
Read the full study in Cephalalgia (2016 Nov 7. doi: 10.1177/0333102416678623).
Novel antibiotic hits skin and soft tissue infections with one-two punch
NEW ORLEANS – A novel antibiotic in development fared well in terms of efficacy and safety for patients hospitalized for suspected or confirmed Gram-positive acute skin and soft tissue infections, reveals the first reported findings of a phase II, randomized study.
Investigators randomized 122 patients over 18 years of age with wound infections, major cutaneous abscesses, or cellulitis to three different dosing intravenous/oral regimens of gepotidacin (GlaxoSmithKline). Patients in the 750-mg/1,500-mg q12h and 1,000-mg/2,000-mg q8h groups met the primary efficacy endpoint of an 80% or greater clinical success (83% and 92%, respectively) within 2-3 days. A third group, randomized to 1,000-mg/2,000-mg q12h, had a 72% early success rate.
All three groups of patients achieved the primary safety outcome, defined as less than a 2.5% withdrawal rate due to drug-related adverse events during gepotidacin treatment. One patient in the 750-mg q12h group withdrew because of a migraine related to the study drug.
Gepotidacin cleaves bacterial DNA in two places to block replication. “Because of its dual mechanism, there are a lot of potential applications,” Dr. O’Riordan said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Gepotidacin is also being assessed in ongoing gonorrhea, complicated intra-abdominal infections, and urinary tract infection studies.
The researchers in the current study also measured clinical success at post therapy days 12-18. They found 90% of the 750-mg/1,500-mg q12h group, 82% of the 1,000-mg/2,000-mg q8h, and 84% of the 1,000-mg/2,000-mg q12h group achieved the composite efficacy endpoint.
Overall, 84 or 69% of study participants experienced an adverse event. Nausea, diarrhea, and vomiting were the most common mild-to-moderate adverse events associated with the 10 days of gepotidacin treatment. Two serious adverse events not related to treatment also occurred during the study.
The “low adverse events and reproducible resolution of skin infections” in this phase II study support further development of gepotidacin, Dr. O’Riordan said.
Dr. O’Riordan had no relevant disclosures. Some study coauthors are GlaxoSmithKline employees.
NEW ORLEANS – A novel antibiotic in development fared well in terms of efficacy and safety for patients hospitalized for suspected or confirmed Gram-positive acute skin and soft tissue infections, reveals the first reported findings of a phase II, randomized study.
Investigators randomized 122 patients over 18 years of age with wound infections, major cutaneous abscesses, or cellulitis to three different dosing intravenous/oral regimens of gepotidacin (GlaxoSmithKline). Patients in the 750-mg/1,500-mg q12h and 1,000-mg/2,000-mg q8h groups met the primary efficacy endpoint of an 80% or greater clinical success (83% and 92%, respectively) within 2-3 days. A third group, randomized to 1,000-mg/2,000-mg q12h, had a 72% early success rate.
All three groups of patients achieved the primary safety outcome, defined as less than a 2.5% withdrawal rate due to drug-related adverse events during gepotidacin treatment. One patient in the 750-mg q12h group withdrew because of a migraine related to the study drug.
Gepotidacin cleaves bacterial DNA in two places to block replication. “Because of its dual mechanism, there are a lot of potential applications,” Dr. O’Riordan said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Gepotidacin is also being assessed in ongoing gonorrhea, complicated intra-abdominal infections, and urinary tract infection studies.
The researchers in the current study also measured clinical success at post therapy days 12-18. They found 90% of the 750-mg/1,500-mg q12h group, 82% of the 1,000-mg/2,000-mg q8h, and 84% of the 1,000-mg/2,000-mg q12h group achieved the composite efficacy endpoint.
Overall, 84 or 69% of study participants experienced an adverse event. Nausea, diarrhea, and vomiting were the most common mild-to-moderate adverse events associated with the 10 days of gepotidacin treatment. Two serious adverse events not related to treatment also occurred during the study.
The “low adverse events and reproducible resolution of skin infections” in this phase II study support further development of gepotidacin, Dr. O’Riordan said.
Dr. O’Riordan had no relevant disclosures. Some study coauthors are GlaxoSmithKline employees.
NEW ORLEANS – A novel antibiotic in development fared well in terms of efficacy and safety for patients hospitalized for suspected or confirmed Gram-positive acute skin and soft tissue infections, reveals the first reported findings of a phase II, randomized study.
Investigators randomized 122 patients over 18 years of age with wound infections, major cutaneous abscesses, or cellulitis to three different dosing intravenous/oral regimens of gepotidacin (GlaxoSmithKline). Patients in the 750-mg/1,500-mg q12h and 1,000-mg/2,000-mg q8h groups met the primary efficacy endpoint of an 80% or greater clinical success (83% and 92%, respectively) within 2-3 days. A third group, randomized to 1,000-mg/2,000-mg q12h, had a 72% early success rate.
All three groups of patients achieved the primary safety outcome, defined as less than a 2.5% withdrawal rate due to drug-related adverse events during gepotidacin treatment. One patient in the 750-mg q12h group withdrew because of a migraine related to the study drug.
Gepotidacin cleaves bacterial DNA in two places to block replication. “Because of its dual mechanism, there are a lot of potential applications,” Dr. O’Riordan said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Gepotidacin is also being assessed in ongoing gonorrhea, complicated intra-abdominal infections, and urinary tract infection studies.
The researchers in the current study also measured clinical success at post therapy days 12-18. They found 90% of the 750-mg/1,500-mg q12h group, 82% of the 1,000-mg/2,000-mg q8h, and 84% of the 1,000-mg/2,000-mg q12h group achieved the composite efficacy endpoint.
Overall, 84 or 69% of study participants experienced an adverse event. Nausea, diarrhea, and vomiting were the most common mild-to-moderate adverse events associated with the 10 days of gepotidacin treatment. Two serious adverse events not related to treatment also occurred during the study.
The “low adverse events and reproducible resolution of skin infections” in this phase II study support further development of gepotidacin, Dr. O’Riordan said.
Dr. O’Riordan had no relevant disclosures. Some study coauthors are GlaxoSmithKline employees.
AT IDWEEK 2016
Key clinical point: A dual-mechanism-of-action antibiotic in development shows good efficacy and a low adverse event rate in a phase II study.
Major finding: A total 71 of 122 adult patients achieved clinical success within 48 to 72 hours with gepotidacin treatment.
Data source: 122 patients over 18 years of age with wound infections, major cutaneous abscesses, or cellulitis.
Disclosures: Dr. O’Riordan had no relevant disclosures. Some study coauthors are GlaxoSmithKline employees.
Investigational AML drugs boosted remission rates
Two investigational drugs appear to be improving outcomes for patients with acute myeloid leukemia (AML), based on results reported in separate abstracts of studies that will be featured at press conferences to be held during the annual meeting of the American Society of Hematology.
In the first study, induction therapy with the investigational drug CPX-351 (Vyxeos), a liposomal formulation of cytarabine and daunorubicin, allowed a higher proportion of patients over age 60 with secondary AML to qualify for allogeneic hematopoietic cell transplants. Those patients went on to have improved survival, compared with patients who received standard 7+3 cytarabine and daunorubicin, Jeffrey E. Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, and his colleagues reported in abstract 906.
The finding that CPX-351 may be an effective bridge to successful transplant for older patients with newly diagnosed secondary AML comes from an exploratory analysis of a phase III study comparing induction therapy with CPX-351 and standard cytarabine and daunorubicin. Initial data from the randomized open-label study, reported last June at the annual meeting of the American Society of Clinical Oncology, indicated CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events, compared with the standard 7+3 regimen of cytarabine and daunorubicin.
The data to be presented at ASH 2016 will examine the outcomes of 52 patients in the CPX-351 arm and 39 patients in the standard cytarabine and daunorubicin arm who underwent allogeneic hematopoietic cell transplantation (HCT) after induction. Data reported in the abstract indicate that 18 of the 52 patients in the CPX-351 arm and 26 of the 39 patients in the standard cytarabine and daunorubicin arm have died. The median survival time was 10.25 months with standard therapy; median survival has not yet been reached in the CPX-351 arm. The results indicate 53% fewer deaths occurred within 100 days of transplant in the CPX-351 group.
Newly diagnosed secondary AML was defined as having a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) with or without prior treatment with hypomethylating agents, or AML with World Health Organization–defined MDS-related cytogenetic abnormalities.
For the trial, conducted over 2 years at 39 U.S. and Canadian sites, 153 patients were randomized to the CPX-351 arm and 156 randomized to the standard therapy arm. Of 125 patients who had a complete response (CR) or a CR with incomplete (CRi) platelet or neutrophil recovery, 91 underwent allogeneic HCT: 52 (34%) from the CPX-351 arm and 39 (25%) from the standard therapy arm. Each arm had a similar percentage of patients who underwent transplant in CR/CRi status; however, the CPX-351 arm contained a higher percentage of patients age 70 and older (31% vs. 15%). Mortality at 100 days after transplant was 9.6% for patients in the CPX-351 arm and 20.5% for patients in the standard therapy arm. Deaths that occurred within 100 days after allogeneic HCT were due to refractory AML (CPX-351, 3.8%; standard therapy, 7.7%); graft vs. host disease (CPX-351, 3.8%; standard therapy, 2.6%); or renal, respiratory, or multiorgan failure, or septic shock (CPX-351, 0 for each; standard therapy, 2.6% for each), or the cause of death was unknown (CPX-351, 1.9%; standard therapy, 0).
For the 91 patients who had transplants, those in the CPX-351 arm had markedly better overall survival (hazard ratio, 0.46; P = .0046). The time-dependent Cox hazard ratio for overall survival in the CPX-351 arm vs. the 7+3 arm was 0.51 (95% confidence interval, 0.35–0.75; P = .0007).
In the phase Ib trial of vadastuximab talirine, 42 patients received the drug on days 1 and 4 of standard 7+3 cytarabine and daunorubicin induction therapy. Most patients had intermediate (40%) or adverse (43%) cytogenetic risk by Medical Research Council criteria, and 17% of patients had secondary AML. Response was assessed on days 15 and 28; MRD was assessed centrally by bone marrow examination using a multiparametric flow cytometric assay. The investigator chose whether to do a second induction regimen and any postremission therapies, which did not include additional administration of vadastuximab talirine.
Of the 40 patients who could be evaluated for efficacy, 24 (60%) had a CR and 7 (18%) had a CRi, and 4 (10%) reached a morphologic leukemia-free state. Nearly all (94%) of CR and CRi responses occurred after one cycle of induction therapy, and 23 of the 31 patients who reached CR or CRi achieved MRD-negative status.
Extramedullary adverse events, including hepatic toxicity, and induction mortality rates were similar to reported rates for 7+3 cytarabine and daunorubicin alone. All patients had grade 4 myelosuppression. In patients who achieved CR or CRi, the estimated median time to count recovery from day 1 of therapy was 33 days for neutrophils and 35 days for platelets. The 30- and 60-day mortality rates were 0% and 7%, respectively.
An alternative schedule of single-day dosing on day 1 is under investigation, and enrollment continues.
The CPX-351 (Vyxeos) study was supported by the drug’s maker, Celator Pharmaceuticals, which is a subsidiary of Jazz Pharmaceuticals. Dr. Lancet is a consultant to Celator as well as numerous other drug companies. Several of his colleagues disclosed a wide variety of relationships with drug companies, including Celator. Two of the study investigators disclosed employment by and equity ownership in Celator.
The vadastuximab talirine study was sponsored by the drug’s maker, Seattle Genetics. Dr. Erba disclosed a wide variety of relationships with drug companies, including research funding from Seattle Genetics. His colleagues had a similar wide variety of relationships, and two disclosed employment by and equity ownership in Seattle Genetics.
Abstract 906 Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated With CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial, will be presented in session 616 at 4:00 p.m. on Monday, Dec. 5.
Abstract 211 A Phase Ib Study of Vadastuximab Talirine in Combination With 7+3 Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) will be presented in session 613 at 4:00 p.m. on Saturday, Dec. 3.
[email protected]
On Twitter @maryjodales
Two investigational drugs appear to be improving outcomes for patients with acute myeloid leukemia (AML), based on results reported in separate abstracts of studies that will be featured at press conferences to be held during the annual meeting of the American Society of Hematology.
In the first study, induction therapy with the investigational drug CPX-351 (Vyxeos), a liposomal formulation of cytarabine and daunorubicin, allowed a higher proportion of patients over age 60 with secondary AML to qualify for allogeneic hematopoietic cell transplants. Those patients went on to have improved survival, compared with patients who received standard 7+3 cytarabine and daunorubicin, Jeffrey E. Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, and his colleagues reported in abstract 906.
The finding that CPX-351 may be an effective bridge to successful transplant for older patients with newly diagnosed secondary AML comes from an exploratory analysis of a phase III study comparing induction therapy with CPX-351 and standard cytarabine and daunorubicin. Initial data from the randomized open-label study, reported last June at the annual meeting of the American Society of Clinical Oncology, indicated CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events, compared with the standard 7+3 regimen of cytarabine and daunorubicin.
The data to be presented at ASH 2016 will examine the outcomes of 52 patients in the CPX-351 arm and 39 patients in the standard cytarabine and daunorubicin arm who underwent allogeneic hematopoietic cell transplantation (HCT) after induction. Data reported in the abstract indicate that 18 of the 52 patients in the CPX-351 arm and 26 of the 39 patients in the standard cytarabine and daunorubicin arm have died. The median survival time was 10.25 months with standard therapy; median survival has not yet been reached in the CPX-351 arm. The results indicate 53% fewer deaths occurred within 100 days of transplant in the CPX-351 group.
Newly diagnosed secondary AML was defined as having a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) with or without prior treatment with hypomethylating agents, or AML with World Health Organization–defined MDS-related cytogenetic abnormalities.
For the trial, conducted over 2 years at 39 U.S. and Canadian sites, 153 patients were randomized to the CPX-351 arm and 156 randomized to the standard therapy arm. Of 125 patients who had a complete response (CR) or a CR with incomplete (CRi) platelet or neutrophil recovery, 91 underwent allogeneic HCT: 52 (34%) from the CPX-351 arm and 39 (25%) from the standard therapy arm. Each arm had a similar percentage of patients who underwent transplant in CR/CRi status; however, the CPX-351 arm contained a higher percentage of patients age 70 and older (31% vs. 15%). Mortality at 100 days after transplant was 9.6% for patients in the CPX-351 arm and 20.5% for patients in the standard therapy arm. Deaths that occurred within 100 days after allogeneic HCT were due to refractory AML (CPX-351, 3.8%; standard therapy, 7.7%); graft vs. host disease (CPX-351, 3.8%; standard therapy, 2.6%); or renal, respiratory, or multiorgan failure, or septic shock (CPX-351, 0 for each; standard therapy, 2.6% for each), or the cause of death was unknown (CPX-351, 1.9%; standard therapy, 0).
For the 91 patients who had transplants, those in the CPX-351 arm had markedly better overall survival (hazard ratio, 0.46; P = .0046). The time-dependent Cox hazard ratio for overall survival in the CPX-351 arm vs. the 7+3 arm was 0.51 (95% confidence interval, 0.35–0.75; P = .0007).
In the phase Ib trial of vadastuximab talirine, 42 patients received the drug on days 1 and 4 of standard 7+3 cytarabine and daunorubicin induction therapy. Most patients had intermediate (40%) or adverse (43%) cytogenetic risk by Medical Research Council criteria, and 17% of patients had secondary AML. Response was assessed on days 15 and 28; MRD was assessed centrally by bone marrow examination using a multiparametric flow cytometric assay. The investigator chose whether to do a second induction regimen and any postremission therapies, which did not include additional administration of vadastuximab talirine.
Of the 40 patients who could be evaluated for efficacy, 24 (60%) had a CR and 7 (18%) had a CRi, and 4 (10%) reached a morphologic leukemia-free state. Nearly all (94%) of CR and CRi responses occurred after one cycle of induction therapy, and 23 of the 31 patients who reached CR or CRi achieved MRD-negative status.
Extramedullary adverse events, including hepatic toxicity, and induction mortality rates were similar to reported rates for 7+3 cytarabine and daunorubicin alone. All patients had grade 4 myelosuppression. In patients who achieved CR or CRi, the estimated median time to count recovery from day 1 of therapy was 33 days for neutrophils and 35 days for platelets. The 30- and 60-day mortality rates were 0% and 7%, respectively.
An alternative schedule of single-day dosing on day 1 is under investigation, and enrollment continues.
The CPX-351 (Vyxeos) study was supported by the drug’s maker, Celator Pharmaceuticals, which is a subsidiary of Jazz Pharmaceuticals. Dr. Lancet is a consultant to Celator as well as numerous other drug companies. Several of his colleagues disclosed a wide variety of relationships with drug companies, including Celator. Two of the study investigators disclosed employment by and equity ownership in Celator.
The vadastuximab talirine study was sponsored by the drug’s maker, Seattle Genetics. Dr. Erba disclosed a wide variety of relationships with drug companies, including research funding from Seattle Genetics. His colleagues had a similar wide variety of relationships, and two disclosed employment by and equity ownership in Seattle Genetics.
Abstract 906 Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated With CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial, will be presented in session 616 at 4:00 p.m. on Monday, Dec. 5.
Abstract 211 A Phase Ib Study of Vadastuximab Talirine in Combination With 7+3 Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) will be presented in session 613 at 4:00 p.m. on Saturday, Dec. 3.
[email protected]
On Twitter @maryjodales
Two investigational drugs appear to be improving outcomes for patients with acute myeloid leukemia (AML), based on results reported in separate abstracts of studies that will be featured at press conferences to be held during the annual meeting of the American Society of Hematology.
In the first study, induction therapy with the investigational drug CPX-351 (Vyxeos), a liposomal formulation of cytarabine and daunorubicin, allowed a higher proportion of patients over age 60 with secondary AML to qualify for allogeneic hematopoietic cell transplants. Those patients went on to have improved survival, compared with patients who received standard 7+3 cytarabine and daunorubicin, Jeffrey E. Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, and his colleagues reported in abstract 906.
The finding that CPX-351 may be an effective bridge to successful transplant for older patients with newly diagnosed secondary AML comes from an exploratory analysis of a phase III study comparing induction therapy with CPX-351 and standard cytarabine and daunorubicin. Initial data from the randomized open-label study, reported last June at the annual meeting of the American Society of Clinical Oncology, indicated CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events, compared with the standard 7+3 regimen of cytarabine and daunorubicin.
The data to be presented at ASH 2016 will examine the outcomes of 52 patients in the CPX-351 arm and 39 patients in the standard cytarabine and daunorubicin arm who underwent allogeneic hematopoietic cell transplantation (HCT) after induction. Data reported in the abstract indicate that 18 of the 52 patients in the CPX-351 arm and 26 of the 39 patients in the standard cytarabine and daunorubicin arm have died. The median survival time was 10.25 months with standard therapy; median survival has not yet been reached in the CPX-351 arm. The results indicate 53% fewer deaths occurred within 100 days of transplant in the CPX-351 group.
Newly diagnosed secondary AML was defined as having a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) with or without prior treatment with hypomethylating agents, or AML with World Health Organization–defined MDS-related cytogenetic abnormalities.
For the trial, conducted over 2 years at 39 U.S. and Canadian sites, 153 patients were randomized to the CPX-351 arm and 156 randomized to the standard therapy arm. Of 125 patients who had a complete response (CR) or a CR with incomplete (CRi) platelet or neutrophil recovery, 91 underwent allogeneic HCT: 52 (34%) from the CPX-351 arm and 39 (25%) from the standard therapy arm. Each arm had a similar percentage of patients who underwent transplant in CR/CRi status; however, the CPX-351 arm contained a higher percentage of patients age 70 and older (31% vs. 15%). Mortality at 100 days after transplant was 9.6% for patients in the CPX-351 arm and 20.5% for patients in the standard therapy arm. Deaths that occurred within 100 days after allogeneic HCT were due to refractory AML (CPX-351, 3.8%; standard therapy, 7.7%); graft vs. host disease (CPX-351, 3.8%; standard therapy, 2.6%); or renal, respiratory, or multiorgan failure, or septic shock (CPX-351, 0 for each; standard therapy, 2.6% for each), or the cause of death was unknown (CPX-351, 1.9%; standard therapy, 0).
For the 91 patients who had transplants, those in the CPX-351 arm had markedly better overall survival (hazard ratio, 0.46; P = .0046). The time-dependent Cox hazard ratio for overall survival in the CPX-351 arm vs. the 7+3 arm was 0.51 (95% confidence interval, 0.35–0.75; P = .0007).
In the phase Ib trial of vadastuximab talirine, 42 patients received the drug on days 1 and 4 of standard 7+3 cytarabine and daunorubicin induction therapy. Most patients had intermediate (40%) or adverse (43%) cytogenetic risk by Medical Research Council criteria, and 17% of patients had secondary AML. Response was assessed on days 15 and 28; MRD was assessed centrally by bone marrow examination using a multiparametric flow cytometric assay. The investigator chose whether to do a second induction regimen and any postremission therapies, which did not include additional administration of vadastuximab talirine.
Of the 40 patients who could be evaluated for efficacy, 24 (60%) had a CR and 7 (18%) had a CRi, and 4 (10%) reached a morphologic leukemia-free state. Nearly all (94%) of CR and CRi responses occurred after one cycle of induction therapy, and 23 of the 31 patients who reached CR or CRi achieved MRD-negative status.
Extramedullary adverse events, including hepatic toxicity, and induction mortality rates were similar to reported rates for 7+3 cytarabine and daunorubicin alone. All patients had grade 4 myelosuppression. In patients who achieved CR or CRi, the estimated median time to count recovery from day 1 of therapy was 33 days for neutrophils and 35 days for platelets. The 30- and 60-day mortality rates were 0% and 7%, respectively.
An alternative schedule of single-day dosing on day 1 is under investigation, and enrollment continues.
The CPX-351 (Vyxeos) study was supported by the drug’s maker, Celator Pharmaceuticals, which is a subsidiary of Jazz Pharmaceuticals. Dr. Lancet is a consultant to Celator as well as numerous other drug companies. Several of his colleagues disclosed a wide variety of relationships with drug companies, including Celator. Two of the study investigators disclosed employment by and equity ownership in Celator.
The vadastuximab talirine study was sponsored by the drug’s maker, Seattle Genetics. Dr. Erba disclosed a wide variety of relationships with drug companies, including research funding from Seattle Genetics. His colleagues had a similar wide variety of relationships, and two disclosed employment by and equity ownership in Seattle Genetics.
Abstract 906 Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated With CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial, will be presented in session 616 at 4:00 p.m. on Monday, Dec. 5.
Abstract 211 A Phase Ib Study of Vadastuximab Talirine in Combination With 7+3 Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) will be presented in session 613 at 4:00 p.m. on Saturday, Dec. 3.
[email protected]
On Twitter @maryjodales
FROM ASH 2016
What will the Trump administration mean for medicine?
The Affordable Care Act is in the crosshairs as the transition to the Trump administration begins Nov. 9.
The primary tenet of Donald J. Trump’s health care platform calls for Congress to repeal the ACA.
In fact, Mr. Trump has called for ACA repeal efforts to begin on his administration’s first day.
The Trump administration is likely to find plentiful allies in Congress as both the House and the Senate were projected at press time to have Republican majorities, albeit slim ones. Since the ACA’s passage in 2010, House Republicans have put forward repeal legislation scores of times.
While many medical specialty societies have supported the ACA and other major health care reforms enacted over the last 8 years – Meaningful Use from the HITECH ACT and value-based payment from MACRA among them – large numbers of physicians have chafed under the myriad reporting requirements and administrative hassles.
A recent survey commissioned by the Physicians Foundation and conducted by Merritt Hawkins found that nearly half (48%) of physicians are considering a change of practice – including leaving medicine – in the next 1-3 years. Reasons cited by survey respondents included the MACRA (Medicare Access and CHIP Reauthorization Act of 2015) transition to value-based care, the increased coding required by ICD-10, the growth of physician employment, the continued sale of private practices to hospitals and health systems, the increased number of patients in the system because of the ACA coupled with a shortage of physicians, and the “businessification” of heath care.
“If any of these [changes] occurred in a period of time, it would be impactful,” Walker Ray, MD, president of the Physicians Foundation, said in an interview. “But to have all occur simultaneously, we say now that to be a physician is to feel the ground shaking under your feet. This is the landscape in which the survey was taken.”
Mr. Trump supports several free market reforms to replace repealed provisions of the ACA, as well as address other issues in the health care system. The proposals include the following:
• Foster interstate insurance sales.
• Reinstate the tax deductibility of health insurance premiums.
• Promote the more widespread use of health savings accounts.
• Require price transparency so that patients can shop for medical procedures, exams, and tests.
• Block grant Medicaid to the states.
• Allow patients to import drugs from outside of the United States.
The Trump platform also promises to reduce fraud and waste, as well as save approximately $11 billion annually by not providing health care to illegal immigrants.
Speculation has also begun regarding who might lead health care agencies and policy for the Trump administration. Among the names that have been floated for secretary of Health and Human Services are Ben Carson, MD, the former presidential candidate and retired neurosurgeon; former House Speaker Newt Gingrich (who also has been suggested as a potential secretary of State); as well as Florida Gov. Rick Scott, former chief executive of Columbia/HCA, according to Politico.com.
[email protected]
On Twitter @denisefulton
Gregory Twachtman contributed to this story.
The Affordable Care Act is in the crosshairs as the transition to the Trump administration begins Nov. 9.
The primary tenet of Donald J. Trump’s health care platform calls for Congress to repeal the ACA.
In fact, Mr. Trump has called for ACA repeal efforts to begin on his administration’s first day.
The Trump administration is likely to find plentiful allies in Congress as both the House and the Senate were projected at press time to have Republican majorities, albeit slim ones. Since the ACA’s passage in 2010, House Republicans have put forward repeal legislation scores of times.
While many medical specialty societies have supported the ACA and other major health care reforms enacted over the last 8 years – Meaningful Use from the HITECH ACT and value-based payment from MACRA among them – large numbers of physicians have chafed under the myriad reporting requirements and administrative hassles.
A recent survey commissioned by the Physicians Foundation and conducted by Merritt Hawkins found that nearly half (48%) of physicians are considering a change of practice – including leaving medicine – in the next 1-3 years. Reasons cited by survey respondents included the MACRA (Medicare Access and CHIP Reauthorization Act of 2015) transition to value-based care, the increased coding required by ICD-10, the growth of physician employment, the continued sale of private practices to hospitals and health systems, the increased number of patients in the system because of the ACA coupled with a shortage of physicians, and the “businessification” of heath care.
“If any of these [changes] occurred in a period of time, it would be impactful,” Walker Ray, MD, president of the Physicians Foundation, said in an interview. “But to have all occur simultaneously, we say now that to be a physician is to feel the ground shaking under your feet. This is the landscape in which the survey was taken.”
Mr. Trump supports several free market reforms to replace repealed provisions of the ACA, as well as address other issues in the health care system. The proposals include the following:
• Foster interstate insurance sales.
• Reinstate the tax deductibility of health insurance premiums.
• Promote the more widespread use of health savings accounts.
• Require price transparency so that patients can shop for medical procedures, exams, and tests.
• Block grant Medicaid to the states.
• Allow patients to import drugs from outside of the United States.
The Trump platform also promises to reduce fraud and waste, as well as save approximately $11 billion annually by not providing health care to illegal immigrants.
Speculation has also begun regarding who might lead health care agencies and policy for the Trump administration. Among the names that have been floated for secretary of Health and Human Services are Ben Carson, MD, the former presidential candidate and retired neurosurgeon; former House Speaker Newt Gingrich (who also has been suggested as a potential secretary of State); as well as Florida Gov. Rick Scott, former chief executive of Columbia/HCA, according to Politico.com.
[email protected]
On Twitter @denisefulton
Gregory Twachtman contributed to this story.
The Affordable Care Act is in the crosshairs as the transition to the Trump administration begins Nov. 9.
The primary tenet of Donald J. Trump’s health care platform calls for Congress to repeal the ACA.
In fact, Mr. Trump has called for ACA repeal efforts to begin on his administration’s first day.
The Trump administration is likely to find plentiful allies in Congress as both the House and the Senate were projected at press time to have Republican majorities, albeit slim ones. Since the ACA’s passage in 2010, House Republicans have put forward repeal legislation scores of times.
While many medical specialty societies have supported the ACA and other major health care reforms enacted over the last 8 years – Meaningful Use from the HITECH ACT and value-based payment from MACRA among them – large numbers of physicians have chafed under the myriad reporting requirements and administrative hassles.
A recent survey commissioned by the Physicians Foundation and conducted by Merritt Hawkins found that nearly half (48%) of physicians are considering a change of practice – including leaving medicine – in the next 1-3 years. Reasons cited by survey respondents included the MACRA (Medicare Access and CHIP Reauthorization Act of 2015) transition to value-based care, the increased coding required by ICD-10, the growth of physician employment, the continued sale of private practices to hospitals and health systems, the increased number of patients in the system because of the ACA coupled with a shortage of physicians, and the “businessification” of heath care.
“If any of these [changes] occurred in a period of time, it would be impactful,” Walker Ray, MD, president of the Physicians Foundation, said in an interview. “But to have all occur simultaneously, we say now that to be a physician is to feel the ground shaking under your feet. This is the landscape in which the survey was taken.”
Mr. Trump supports several free market reforms to replace repealed provisions of the ACA, as well as address other issues in the health care system. The proposals include the following:
• Foster interstate insurance sales.
• Reinstate the tax deductibility of health insurance premiums.
• Promote the more widespread use of health savings accounts.
• Require price transparency so that patients can shop for medical procedures, exams, and tests.
• Block grant Medicaid to the states.
• Allow patients to import drugs from outside of the United States.
The Trump platform also promises to reduce fraud and waste, as well as save approximately $11 billion annually by not providing health care to illegal immigrants.
Speculation has also begun regarding who might lead health care agencies and policy for the Trump administration. Among the names that have been floated for secretary of Health and Human Services are Ben Carson, MD, the former presidential candidate and retired neurosurgeon; former House Speaker Newt Gingrich (who also has been suggested as a potential secretary of State); as well as Florida Gov. Rick Scott, former chief executive of Columbia/HCA, according to Politico.com.
[email protected]
On Twitter @denisefulton
Gregory Twachtman contributed to this story.
Everything You Need to Know About the Bundled Payments for Care Improvement Initiative
As far back as 1983 —13 years before the birth of HM—Medicare created what was then called an “inpatient prospective payment system,” which essentially let Medicare pay a fixed amount for the entirety of a hospital stay, based on diagnosis. Then in 1991, the Centers for Medicare & Medicaid Services (CMS) introduced one payment for coronary artery bypass graft surgery, and even included 90-day readmission in the check.
Fast forward to the past 10 years when accountable care organizations (ACOs) and value-based purchasing (VBP) have been the focus of HM executives looking to take the lead in how to make bundled payments work for them.
The Bundled Payments for Care Improvement (BPCI) initiative was introduced by CMS’s Center for Medicare & Medicaid Innovation (CMMI) in 2011 and is now compiling its first data sets for the next frontier of payments for episodic care.
For rank-and-file hospitalists who have felt inundated by the regulations and promised payment reforms from ACOs and VBPs, why is this program so important?
“The reason this is so special is that it is one of the few CMS programs that allows providers to be in the driver’s seat,” says Kerry Weiner, MD, chief medical officer of acute and post-acute services at TeamHealth-IPC The Hospitalist Company. “They have the opportunity to be accountable and to actually be the designers of reengineering care. The other programs that you just mentioned, like value-based purchasing, largely originate from health systems or the federal government and dictate the principles and the metrics that as a provider you’re going to be evaluated upon.
“This model, the bundled model, gives us the flexibility, scale and brackets of risk that we want to accept and thereby gives us a lot more control over what physicians and physician groups can manage successfully.”
BPCI might be a game-changer for HM because it’s the first of the bundled-payment initiatives that truly falls direct to the care provided by hospitalists. In short, the plan covers 48 defined episodes of care and would parse out payments for those episodes in a holistic—and some say more appropriate—way. Currently, a hospitalist would get paid for a patient’s stay in the hospital and a primary-care physician (PCP) could be paid for some follow-up. If the patient ends up back in the hospital quickly, the hospitalist could get paid again and, upon discharge, a PCP could, too.
But under BPCI, pay would be determined based on the episode of care. The details of who gets paid what and the rules that apply are all likely to evolve, of course, but it’s hoped the basic premise of bundled payments would lower the overall cost of healthcare.
How It Works
Under the Patient Protection and Affordable Care Act (ACA) of 2009, it was mandated that the government establish a five-year pilot program by 2013 that bundled payments for inpatient care, according to the American Hospital Association.
The program has now ramped up to include more than 650 participating organization, not including thousands of physicians that then partner with those groups, over four models. The initiative covers defined episodes of care, both medical and surgical, that begin at the time of inpatient admission and stretch 30, 60 or 90 days post-discharge.
And hospitalists are poised to take the lead on how payment models, especially bundled payments, are shaped over the next few years, says John Nelson, MD, MHM, a co-founder and past president of SHM and and principal in Nelson Flores Hospital Medicine Consultants in Bellevue, Wash. Nelson says his consulting firm has seen an uptick in calls over the past two years dealing with alternative payment models (APMs).
“Hospitalists find themselves at a vitally important nexus of performance and success on new payment models,” he adds.
Win Whitcomb, MD, MHM, chief medical officer of Remedy Partners in Darien, Conn., agrees that BPCI and future iterations of bundled payment programs “are likely to be a potent driver of an evolving hospitalist specialty.” His hypothesis is that APMs such as BPCI are an important way for Medicare to reach its stated goal of having 50% of its fee-for-service payments running through APMs by the end of 2018. To further entice that process, physicians who document at least 25% of their revenue as coming through APMs will get a 5% bonus.
“The stakes are high now,” says Dr. Whitcomb, a past SHM president whose employer is an Awardee Convener in the BPCI initiative, meaning it administers the program. “Medicare [has] laid out the
course for the next two and a half, three years and beyond… It will be crucial for hospitalists to have a path to participate broadly in APMs..”
Dr. Whitcomb says BPCI is the program that should excite hospitalists most because it is more applicable to them moving forward than ACOs, heralded by many healthcare executives several years ago as the future of payment reform.
“With a focus on ambulatory care, ACOs have not broadly involved hospitalists,” he says. “If you look at the State of Hospital Medicine surveys, you look at how many hospitalists are meaningfully working at a system level on ACOs and committees and so forth to improve the performance of the ACO, and it’s very low.”
In fact, just 13.9% of HM groups serving adults only had formed or were participating in a functioning ACO, according to SHM’s 2014 State of Hospital Medicine report. Another 6% were in the process of forming or participating, the paper reported.
“ACOs have not yet widely worked alongside hospitalist teams to optimize where patients go after hospitalization, which is arguably the most important way to deal with post-acute-care utilization” Dr. Whitcomb adds. “whereas nearly all hospitalists working in bundle payments are focusing on a ‘high-value’ transition out of the hospital.”
Improving Care
While BPCI is focused on payment structure, the program could breed process improvements as well as improve care, says hospitalist Patrick Conway, MD, MHM, MSc, CMS’s chief medical officer and deputy administrator for innovation and quality.
“In addition to assessing the quality of patient outcomes and patient experience, CMS is also monitoring for unintended consequences, including whether there is an increase in the number of specific clinical episodes [such as specific elective surgeries] that would not have been expected in the absence of BPCI,” Dr. Conway says. “CMS can audit and intervene if it detects unintended negative consequences for beneficiaries.”
Dr. Whitcomb says two main ways that hospitalists can use BPCI to calculate value is by having better metrics on post-acute facility utilization and reduced readmission.
Immediate past SHM President Robert Harrington Jr., MD, SFHM, says that BPCI is a major stepping stone to merging quality and payment, along the lines of using Physician Quality Reporting System (PQRS) data in the value-based payment modifier.
“CMS is saying to all of us in the provider world, ‘We want to get out of the business of unit economics, and we want to start paying for episodes of care and providers should be at risk for quality outcomes,” he says. “BPCI, to me, is one of the rungs in the ladder.”
Dr. Harrington, chief medical officer at Reliant Post-Acute Care Solutions in Atlanta, says that the program’s inclusion of acute-care hospitals, skilled nursing facilities (SNFs), physician group practices, long-term care hospitals, inpatient rehabilitation facilities, and home health agencies working together is what differentiates it from past attempts at payment reform.
“Population health is sort of where this is headed,” he adds. “You sit in a CFO seat at a hospital or healthcare system right now, and five years ago, they’d buy an MRI machine and they wanted throughput through that MRI machine and they wanted as many people run through that MRI machine in the fee-for-service world as they could get to go through that machine. Nowadays, you start to look at it from a population health standpoint and the CFO is going to say to you, ‘I don’t want anybody going through that MRI machine unless they have to.’
“So it’s a total reversal of perspective when hospitals either become joined at the hip with the payors or become the payors and they start taking risk on population health and I think BPCI is one way that Medicare has allowed all of us to test the waters and get comfortable with that.”
Getting Involved
Dr. Weiner is aware that some hospitalists are nervous about bundled payments because their reimbursement is, in part based on care provided outside of their control. Take a surgical procedure where a hospitalist managing the post-surgery care is left to deal with any potential mistakes made. Or the process works fine until there is poor management by ambulatory care once the patient is discharged.
“That is the reason this program exists,” he says. “It poses the question, who is going to be accountable for the care outside of the traditional site of care that providers have been practicing in, your traditional boundaries? I would argue that physicians are more or are just as valuable as any other segment of the healthcare system in managing the transitions of care and in managing the gaps in the system.”
Given how HM has moved into post-discharge care via SNFs and other post-acute care facilities in recent years, Dr. Weiner says that while hospitalists can’t actually deliver all of the care in an “episode,” they can shepherd that process.
Hospitalists “have control over where the patient goes after they leave the acute-care facility, for example,” he says. “They write the orders on what level of care is needed, and they should have the intimate knowledge about what’s available in their community to ensure the patient gets the best care possible. As long as they have the accountability and the power to direct care, then they have the ability to negotiate and recommend care that is best for the patient, so they can select the better facilities in the community, the better agencies in the community, the better resources in the community to ensure that there is better care once the patient leaves the hospital.”
Dr. Conway suggests HM practitioners view BPCI as a model based on “quality and value.” He says early participants helped define clinical episodes, length of episode, and risk track, making the program better suited to address the actual needs of hospitalists.
“I would encourage hospital medicine physicians and care teams to view bundled payment models as an opportunity for them and their patients for better care and smarter spending,” he adds. “CMS continues to explore ways to pay for value and not just volume. Many of the organizations that are participating in BPCI have partnered with their physician communities and established gainsharing agreement. …Most importantly, this model focuses on care coordination for patients across episodes of care.
And that’s the key for Dr. Weiner.
Hospitalists who embrace BPCI can shape it as the predominant inpatient funding model for hospitals over the next five or 10 years. HM administrators and practitioners who don’t seize the opportunity to flesh out the program tacitly cede control to people outside the hospital who may not tailor the program nearly as well, he says.
“Those who have accountability in the end, the systems, the people, the entities, the providers that have the ability, the accountability for it will ultimately design it,” Dr. Weiner adds. “I think physicians, especially hospitalists, should be at that table. We should play an active role in designing the system.” TH
Richard Quinn is a freelance writer in New Jersey.
The ABCs of $$$s
- APM: Alternative payment models. The catch-all phrase for a variety of programs and initiatives that are outside the traditional fee-for-service model.
- MACRA: Medicare Access & CHIP Reauthorization Act of 2015. The act ended the hated sustainable growth rate (SGR) formula and combined CMS’s existing quality reporting programs under one system.
- MIPS: Merit-Based Incentive Payment System. The new program combines parts of the Physician Quality Reporting System (PQRS), the value modifier (VM, or value-based payment modifier/VBPM), and the Medicare electronic health record (EHR) incentive program into a single program.
Source: Centers for Medicare & Medicaid Services
—By Richard Quinn
As far back as 1983 —13 years before the birth of HM—Medicare created what was then called an “inpatient prospective payment system,” which essentially let Medicare pay a fixed amount for the entirety of a hospital stay, based on diagnosis. Then in 1991, the Centers for Medicare & Medicaid Services (CMS) introduced one payment for coronary artery bypass graft surgery, and even included 90-day readmission in the check.
Fast forward to the past 10 years when accountable care organizations (ACOs) and value-based purchasing (VBP) have been the focus of HM executives looking to take the lead in how to make bundled payments work for them.
The Bundled Payments for Care Improvement (BPCI) initiative was introduced by CMS’s Center for Medicare & Medicaid Innovation (CMMI) in 2011 and is now compiling its first data sets for the next frontier of payments for episodic care.
For rank-and-file hospitalists who have felt inundated by the regulations and promised payment reforms from ACOs and VBPs, why is this program so important?
“The reason this is so special is that it is one of the few CMS programs that allows providers to be in the driver’s seat,” says Kerry Weiner, MD, chief medical officer of acute and post-acute services at TeamHealth-IPC The Hospitalist Company. “They have the opportunity to be accountable and to actually be the designers of reengineering care. The other programs that you just mentioned, like value-based purchasing, largely originate from health systems or the federal government and dictate the principles and the metrics that as a provider you’re going to be evaluated upon.
“This model, the bundled model, gives us the flexibility, scale and brackets of risk that we want to accept and thereby gives us a lot more control over what physicians and physician groups can manage successfully.”
BPCI might be a game-changer for HM because it’s the first of the bundled-payment initiatives that truly falls direct to the care provided by hospitalists. In short, the plan covers 48 defined episodes of care and would parse out payments for those episodes in a holistic—and some say more appropriate—way. Currently, a hospitalist would get paid for a patient’s stay in the hospital and a primary-care physician (PCP) could be paid for some follow-up. If the patient ends up back in the hospital quickly, the hospitalist could get paid again and, upon discharge, a PCP could, too.
But under BPCI, pay would be determined based on the episode of care. The details of who gets paid what and the rules that apply are all likely to evolve, of course, but it’s hoped the basic premise of bundled payments would lower the overall cost of healthcare.
How It Works
Under the Patient Protection and Affordable Care Act (ACA) of 2009, it was mandated that the government establish a five-year pilot program by 2013 that bundled payments for inpatient care, according to the American Hospital Association.
The program has now ramped up to include more than 650 participating organization, not including thousands of physicians that then partner with those groups, over four models. The initiative covers defined episodes of care, both medical and surgical, that begin at the time of inpatient admission and stretch 30, 60 or 90 days post-discharge.
And hospitalists are poised to take the lead on how payment models, especially bundled payments, are shaped over the next few years, says John Nelson, MD, MHM, a co-founder and past president of SHM and and principal in Nelson Flores Hospital Medicine Consultants in Bellevue, Wash. Nelson says his consulting firm has seen an uptick in calls over the past two years dealing with alternative payment models (APMs).
“Hospitalists find themselves at a vitally important nexus of performance and success on new payment models,” he adds.
Win Whitcomb, MD, MHM, chief medical officer of Remedy Partners in Darien, Conn., agrees that BPCI and future iterations of bundled payment programs “are likely to be a potent driver of an evolving hospitalist specialty.” His hypothesis is that APMs such as BPCI are an important way for Medicare to reach its stated goal of having 50% of its fee-for-service payments running through APMs by the end of 2018. To further entice that process, physicians who document at least 25% of their revenue as coming through APMs will get a 5% bonus.
“The stakes are high now,” says Dr. Whitcomb, a past SHM president whose employer is an Awardee Convener in the BPCI initiative, meaning it administers the program. “Medicare [has] laid out the
course for the next two and a half, three years and beyond… It will be crucial for hospitalists to have a path to participate broadly in APMs..”
Dr. Whitcomb says BPCI is the program that should excite hospitalists most because it is more applicable to them moving forward than ACOs, heralded by many healthcare executives several years ago as the future of payment reform.
“With a focus on ambulatory care, ACOs have not broadly involved hospitalists,” he says. “If you look at the State of Hospital Medicine surveys, you look at how many hospitalists are meaningfully working at a system level on ACOs and committees and so forth to improve the performance of the ACO, and it’s very low.”
In fact, just 13.9% of HM groups serving adults only had formed or were participating in a functioning ACO, according to SHM’s 2014 State of Hospital Medicine report. Another 6% were in the process of forming or participating, the paper reported.
“ACOs have not yet widely worked alongside hospitalist teams to optimize where patients go after hospitalization, which is arguably the most important way to deal with post-acute-care utilization” Dr. Whitcomb adds. “whereas nearly all hospitalists working in bundle payments are focusing on a ‘high-value’ transition out of the hospital.”
Improving Care
While BPCI is focused on payment structure, the program could breed process improvements as well as improve care, says hospitalist Patrick Conway, MD, MHM, MSc, CMS’s chief medical officer and deputy administrator for innovation and quality.
“In addition to assessing the quality of patient outcomes and patient experience, CMS is also monitoring for unintended consequences, including whether there is an increase in the number of specific clinical episodes [such as specific elective surgeries] that would not have been expected in the absence of BPCI,” Dr. Conway says. “CMS can audit and intervene if it detects unintended negative consequences for beneficiaries.”
Dr. Whitcomb says two main ways that hospitalists can use BPCI to calculate value is by having better metrics on post-acute facility utilization and reduced readmission.
Immediate past SHM President Robert Harrington Jr., MD, SFHM, says that BPCI is a major stepping stone to merging quality and payment, along the lines of using Physician Quality Reporting System (PQRS) data in the value-based payment modifier.
“CMS is saying to all of us in the provider world, ‘We want to get out of the business of unit economics, and we want to start paying for episodes of care and providers should be at risk for quality outcomes,” he says. “BPCI, to me, is one of the rungs in the ladder.”
Dr. Harrington, chief medical officer at Reliant Post-Acute Care Solutions in Atlanta, says that the program’s inclusion of acute-care hospitals, skilled nursing facilities (SNFs), physician group practices, long-term care hospitals, inpatient rehabilitation facilities, and home health agencies working together is what differentiates it from past attempts at payment reform.
“Population health is sort of where this is headed,” he adds. “You sit in a CFO seat at a hospital or healthcare system right now, and five years ago, they’d buy an MRI machine and they wanted throughput through that MRI machine and they wanted as many people run through that MRI machine in the fee-for-service world as they could get to go through that machine. Nowadays, you start to look at it from a population health standpoint and the CFO is going to say to you, ‘I don’t want anybody going through that MRI machine unless they have to.’
“So it’s a total reversal of perspective when hospitals either become joined at the hip with the payors or become the payors and they start taking risk on population health and I think BPCI is one way that Medicare has allowed all of us to test the waters and get comfortable with that.”
Getting Involved
Dr. Weiner is aware that some hospitalists are nervous about bundled payments because their reimbursement is, in part based on care provided outside of their control. Take a surgical procedure where a hospitalist managing the post-surgery care is left to deal with any potential mistakes made. Or the process works fine until there is poor management by ambulatory care once the patient is discharged.
“That is the reason this program exists,” he says. “It poses the question, who is going to be accountable for the care outside of the traditional site of care that providers have been practicing in, your traditional boundaries? I would argue that physicians are more or are just as valuable as any other segment of the healthcare system in managing the transitions of care and in managing the gaps in the system.”
Given how HM has moved into post-discharge care via SNFs and other post-acute care facilities in recent years, Dr. Weiner says that while hospitalists can’t actually deliver all of the care in an “episode,” they can shepherd that process.
Hospitalists “have control over where the patient goes after they leave the acute-care facility, for example,” he says. “They write the orders on what level of care is needed, and they should have the intimate knowledge about what’s available in their community to ensure the patient gets the best care possible. As long as they have the accountability and the power to direct care, then they have the ability to negotiate and recommend care that is best for the patient, so they can select the better facilities in the community, the better agencies in the community, the better resources in the community to ensure that there is better care once the patient leaves the hospital.”
Dr. Conway suggests HM practitioners view BPCI as a model based on “quality and value.” He says early participants helped define clinical episodes, length of episode, and risk track, making the program better suited to address the actual needs of hospitalists.
“I would encourage hospital medicine physicians and care teams to view bundled payment models as an opportunity for them and their patients for better care and smarter spending,” he adds. “CMS continues to explore ways to pay for value and not just volume. Many of the organizations that are participating in BPCI have partnered with their physician communities and established gainsharing agreement. …Most importantly, this model focuses on care coordination for patients across episodes of care.
And that’s the key for Dr. Weiner.
Hospitalists who embrace BPCI can shape it as the predominant inpatient funding model for hospitals over the next five or 10 years. HM administrators and practitioners who don’t seize the opportunity to flesh out the program tacitly cede control to people outside the hospital who may not tailor the program nearly as well, he says.
“Those who have accountability in the end, the systems, the people, the entities, the providers that have the ability, the accountability for it will ultimately design it,” Dr. Weiner adds. “I think physicians, especially hospitalists, should be at that table. We should play an active role in designing the system.” TH
Richard Quinn is a freelance writer in New Jersey.
The ABCs of $$$s
- APM: Alternative payment models. The catch-all phrase for a variety of programs and initiatives that are outside the traditional fee-for-service model.
- MACRA: Medicare Access & CHIP Reauthorization Act of 2015. The act ended the hated sustainable growth rate (SGR) formula and combined CMS’s existing quality reporting programs under one system.
- MIPS: Merit-Based Incentive Payment System. The new program combines parts of the Physician Quality Reporting System (PQRS), the value modifier (VM, or value-based payment modifier/VBPM), and the Medicare electronic health record (EHR) incentive program into a single program.
Source: Centers for Medicare & Medicaid Services
—By Richard Quinn
As far back as 1983 —13 years before the birth of HM—Medicare created what was then called an “inpatient prospective payment system,” which essentially let Medicare pay a fixed amount for the entirety of a hospital stay, based on diagnosis. Then in 1991, the Centers for Medicare & Medicaid Services (CMS) introduced one payment for coronary artery bypass graft surgery, and even included 90-day readmission in the check.
Fast forward to the past 10 years when accountable care organizations (ACOs) and value-based purchasing (VBP) have been the focus of HM executives looking to take the lead in how to make bundled payments work for them.
The Bundled Payments for Care Improvement (BPCI) initiative was introduced by CMS’s Center for Medicare & Medicaid Innovation (CMMI) in 2011 and is now compiling its first data sets for the next frontier of payments for episodic care.
For rank-and-file hospitalists who have felt inundated by the regulations and promised payment reforms from ACOs and VBPs, why is this program so important?
“The reason this is so special is that it is one of the few CMS programs that allows providers to be in the driver’s seat,” says Kerry Weiner, MD, chief medical officer of acute and post-acute services at TeamHealth-IPC The Hospitalist Company. “They have the opportunity to be accountable and to actually be the designers of reengineering care. The other programs that you just mentioned, like value-based purchasing, largely originate from health systems or the federal government and dictate the principles and the metrics that as a provider you’re going to be evaluated upon.
“This model, the bundled model, gives us the flexibility, scale and brackets of risk that we want to accept and thereby gives us a lot more control over what physicians and physician groups can manage successfully.”
BPCI might be a game-changer for HM because it’s the first of the bundled-payment initiatives that truly falls direct to the care provided by hospitalists. In short, the plan covers 48 defined episodes of care and would parse out payments for those episodes in a holistic—and some say more appropriate—way. Currently, a hospitalist would get paid for a patient’s stay in the hospital and a primary-care physician (PCP) could be paid for some follow-up. If the patient ends up back in the hospital quickly, the hospitalist could get paid again and, upon discharge, a PCP could, too.
But under BPCI, pay would be determined based on the episode of care. The details of who gets paid what and the rules that apply are all likely to evolve, of course, but it’s hoped the basic premise of bundled payments would lower the overall cost of healthcare.
How It Works
Under the Patient Protection and Affordable Care Act (ACA) of 2009, it was mandated that the government establish a five-year pilot program by 2013 that bundled payments for inpatient care, according to the American Hospital Association.
The program has now ramped up to include more than 650 participating organization, not including thousands of physicians that then partner with those groups, over four models. The initiative covers defined episodes of care, both medical and surgical, that begin at the time of inpatient admission and stretch 30, 60 or 90 days post-discharge.
And hospitalists are poised to take the lead on how payment models, especially bundled payments, are shaped over the next few years, says John Nelson, MD, MHM, a co-founder and past president of SHM and and principal in Nelson Flores Hospital Medicine Consultants in Bellevue, Wash. Nelson says his consulting firm has seen an uptick in calls over the past two years dealing with alternative payment models (APMs).
“Hospitalists find themselves at a vitally important nexus of performance and success on new payment models,” he adds.
Win Whitcomb, MD, MHM, chief medical officer of Remedy Partners in Darien, Conn., agrees that BPCI and future iterations of bundled payment programs “are likely to be a potent driver of an evolving hospitalist specialty.” His hypothesis is that APMs such as BPCI are an important way for Medicare to reach its stated goal of having 50% of its fee-for-service payments running through APMs by the end of 2018. To further entice that process, physicians who document at least 25% of their revenue as coming through APMs will get a 5% bonus.
“The stakes are high now,” says Dr. Whitcomb, a past SHM president whose employer is an Awardee Convener in the BPCI initiative, meaning it administers the program. “Medicare [has] laid out the
course for the next two and a half, three years and beyond… It will be crucial for hospitalists to have a path to participate broadly in APMs..”
Dr. Whitcomb says BPCI is the program that should excite hospitalists most because it is more applicable to them moving forward than ACOs, heralded by many healthcare executives several years ago as the future of payment reform.
“With a focus on ambulatory care, ACOs have not broadly involved hospitalists,” he says. “If you look at the State of Hospital Medicine surveys, you look at how many hospitalists are meaningfully working at a system level on ACOs and committees and so forth to improve the performance of the ACO, and it’s very low.”
In fact, just 13.9% of HM groups serving adults only had formed or were participating in a functioning ACO, according to SHM’s 2014 State of Hospital Medicine report. Another 6% were in the process of forming or participating, the paper reported.
“ACOs have not yet widely worked alongside hospitalist teams to optimize where patients go after hospitalization, which is arguably the most important way to deal with post-acute-care utilization” Dr. Whitcomb adds. “whereas nearly all hospitalists working in bundle payments are focusing on a ‘high-value’ transition out of the hospital.”
Improving Care
While BPCI is focused on payment structure, the program could breed process improvements as well as improve care, says hospitalist Patrick Conway, MD, MHM, MSc, CMS’s chief medical officer and deputy administrator for innovation and quality.
“In addition to assessing the quality of patient outcomes and patient experience, CMS is also monitoring for unintended consequences, including whether there is an increase in the number of specific clinical episodes [such as specific elective surgeries] that would not have been expected in the absence of BPCI,” Dr. Conway says. “CMS can audit and intervene if it detects unintended negative consequences for beneficiaries.”
Dr. Whitcomb says two main ways that hospitalists can use BPCI to calculate value is by having better metrics on post-acute facility utilization and reduced readmission.
Immediate past SHM President Robert Harrington Jr., MD, SFHM, says that BPCI is a major stepping stone to merging quality and payment, along the lines of using Physician Quality Reporting System (PQRS) data in the value-based payment modifier.
“CMS is saying to all of us in the provider world, ‘We want to get out of the business of unit economics, and we want to start paying for episodes of care and providers should be at risk for quality outcomes,” he says. “BPCI, to me, is one of the rungs in the ladder.”
Dr. Harrington, chief medical officer at Reliant Post-Acute Care Solutions in Atlanta, says that the program’s inclusion of acute-care hospitals, skilled nursing facilities (SNFs), physician group practices, long-term care hospitals, inpatient rehabilitation facilities, and home health agencies working together is what differentiates it from past attempts at payment reform.
“Population health is sort of where this is headed,” he adds. “You sit in a CFO seat at a hospital or healthcare system right now, and five years ago, they’d buy an MRI machine and they wanted throughput through that MRI machine and they wanted as many people run through that MRI machine in the fee-for-service world as they could get to go through that machine. Nowadays, you start to look at it from a population health standpoint and the CFO is going to say to you, ‘I don’t want anybody going through that MRI machine unless they have to.’
“So it’s a total reversal of perspective when hospitals either become joined at the hip with the payors or become the payors and they start taking risk on population health and I think BPCI is one way that Medicare has allowed all of us to test the waters and get comfortable with that.”
Getting Involved
Dr. Weiner is aware that some hospitalists are nervous about bundled payments because their reimbursement is, in part based on care provided outside of their control. Take a surgical procedure where a hospitalist managing the post-surgery care is left to deal with any potential mistakes made. Or the process works fine until there is poor management by ambulatory care once the patient is discharged.
“That is the reason this program exists,” he says. “It poses the question, who is going to be accountable for the care outside of the traditional site of care that providers have been practicing in, your traditional boundaries? I would argue that physicians are more or are just as valuable as any other segment of the healthcare system in managing the transitions of care and in managing the gaps in the system.”
Given how HM has moved into post-discharge care via SNFs and other post-acute care facilities in recent years, Dr. Weiner says that while hospitalists can’t actually deliver all of the care in an “episode,” they can shepherd that process.
Hospitalists “have control over where the patient goes after they leave the acute-care facility, for example,” he says. “They write the orders on what level of care is needed, and they should have the intimate knowledge about what’s available in their community to ensure the patient gets the best care possible. As long as they have the accountability and the power to direct care, then they have the ability to negotiate and recommend care that is best for the patient, so they can select the better facilities in the community, the better agencies in the community, the better resources in the community to ensure that there is better care once the patient leaves the hospital.”
Dr. Conway suggests HM practitioners view BPCI as a model based on “quality and value.” He says early participants helped define clinical episodes, length of episode, and risk track, making the program better suited to address the actual needs of hospitalists.
“I would encourage hospital medicine physicians and care teams to view bundled payment models as an opportunity for them and their patients for better care and smarter spending,” he adds. “CMS continues to explore ways to pay for value and not just volume. Many of the organizations that are participating in BPCI have partnered with their physician communities and established gainsharing agreement. …Most importantly, this model focuses on care coordination for patients across episodes of care.
And that’s the key for Dr. Weiner.
Hospitalists who embrace BPCI can shape it as the predominant inpatient funding model for hospitals over the next five or 10 years. HM administrators and practitioners who don’t seize the opportunity to flesh out the program tacitly cede control to people outside the hospital who may not tailor the program nearly as well, he says.
“Those who have accountability in the end, the systems, the people, the entities, the providers that have the ability, the accountability for it will ultimately design it,” Dr. Weiner adds. “I think physicians, especially hospitalists, should be at that table. We should play an active role in designing the system.” TH
Richard Quinn is a freelance writer in New Jersey.
The ABCs of $$$s
- APM: Alternative payment models. The catch-all phrase for a variety of programs and initiatives that are outside the traditional fee-for-service model.
- MACRA: Medicare Access & CHIP Reauthorization Act of 2015. The act ended the hated sustainable growth rate (SGR) formula and combined CMS’s existing quality reporting programs under one system.
- MIPS: Merit-Based Incentive Payment System. The new program combines parts of the Physician Quality Reporting System (PQRS), the value modifier (VM, or value-based payment modifier/VBPM), and the Medicare electronic health record (EHR) incentive program into a single program.
Source: Centers for Medicare & Medicaid Services
—By Richard Quinn
Link between hemolysis and infection explained
plate showing a positive
streptococcus infection
Photo by Bill Branson
Patients who suffer from hemolysis have an increased risk of developing bacterial infections, and new research provides an explanation for this phenomenon.
The study refutes the idea that excess circulating iron is to blame.
Instead, it suggests that heme prevents macrophages from engulfing bacteria. And targeting this activity might reduce the risk of bacterial infection in patients with hemolytic disorders.
Sylvia Knapp, MD, PhD, of the Medical University of Vienna in Austria, and her colleagues reported these findings in Nature Immunology.
For decades, iron has been considered the prime suspect responsible for the high rate of bacterial infections in patients with hemolysis. Iron has long been established as an essential nutrient for bacteria.
Since hemolysis leads to the release of iron-containing heme, the threat of serious bacterial infections in these patients was attributed to the excess availability of circulating iron (heme).
However, Dr Knapp and her colleagues found that heme does not act as a willing nutrient to bacteria.
“Using in vitro and preclinical models, we could clearly demonstrate that heme-derived iron is not at all vital for bacterial growth,” said Rui Martins, a PhD student at the Medical University of Vienna.
“In contrast, we found that heme acts on macrophages, the most significant immune cells that are required for mounting an antibacterial response, and it furthermore prevented these cells from eliminating bacteria.”
Heme interfered with the cytoskeleton of macrophages, thereby immobilizing them.
“Heme causes cells to form numerous spikes—like hair standing on end—and then ‘stuns’ the cells within minutes,” Martins explained. “It is reminiscent of a cartoon character sticking his finger in an electrical outlet.”
The cytoskeleton is crucial for the basic functions of macrophages. It consists of long, branching filaments that act as the cell’s internal, highly flexible, and mobile framework.
Through targeted build-up and breakdown of these filaments, phagocytes can move in any direction and engulf invading bacteria. However, this requires a finely tuned signaling program in which the protein DOCK8 plays a central role.
“Through chemical proteomics and biochemical experiments, we discovered that heme interacted with DOCK8, which led to the permanent activation of its downstream target, Cdc42, with deleterious effects,” Dr Knapp said.
In the presence of heme, the cytoskeletal resilience was lost, as filaments grew rampant in all directions, resulting in macrophage paralysis. The cells lost their ability to shape-shift and could no longer chase down and engulf the invading bacteria, allowing the bacteria to multiply virtually unrestricted.
However, Dr Knapp and her colleagues found that an antimalarial drug can restore the functionality of these paralyzed macrophages.
“Quinine, which is clinically used to treat malaria and is suspected to bind heme, blocks the interaction of heme with DOCK8 and thereby improves the outcome from sepsis,” Dr Knapp said.
“This is very promising. We conclusively demonstrate that it is indeed feasible to therapeutically ‘protect’ immune cells and to restore the body’s immune defense against bacteria in hemolytic conditions.” 
plate showing a positive
streptococcus infection
Photo by Bill Branson
Patients who suffer from hemolysis have an increased risk of developing bacterial infections, and new research provides an explanation for this phenomenon.
The study refutes the idea that excess circulating iron is to blame.
Instead, it suggests that heme prevents macrophages from engulfing bacteria. And targeting this activity might reduce the risk of bacterial infection in patients with hemolytic disorders.
Sylvia Knapp, MD, PhD, of the Medical University of Vienna in Austria, and her colleagues reported these findings in Nature Immunology.
For decades, iron has been considered the prime suspect responsible for the high rate of bacterial infections in patients with hemolysis. Iron has long been established as an essential nutrient for bacteria.
Since hemolysis leads to the release of iron-containing heme, the threat of serious bacterial infections in these patients was attributed to the excess availability of circulating iron (heme).
However, Dr Knapp and her colleagues found that heme does not act as a willing nutrient to bacteria.
“Using in vitro and preclinical models, we could clearly demonstrate that heme-derived iron is not at all vital for bacterial growth,” said Rui Martins, a PhD student at the Medical University of Vienna.
“In contrast, we found that heme acts on macrophages, the most significant immune cells that are required for mounting an antibacterial response, and it furthermore prevented these cells from eliminating bacteria.”
Heme interfered with the cytoskeleton of macrophages, thereby immobilizing them.
“Heme causes cells to form numerous spikes—like hair standing on end—and then ‘stuns’ the cells within minutes,” Martins explained. “It is reminiscent of a cartoon character sticking his finger in an electrical outlet.”
The cytoskeleton is crucial for the basic functions of macrophages. It consists of long, branching filaments that act as the cell’s internal, highly flexible, and mobile framework.
Through targeted build-up and breakdown of these filaments, phagocytes can move in any direction and engulf invading bacteria. However, this requires a finely tuned signaling program in which the protein DOCK8 plays a central role.
“Through chemical proteomics and biochemical experiments, we discovered that heme interacted with DOCK8, which led to the permanent activation of its downstream target, Cdc42, with deleterious effects,” Dr Knapp said.
In the presence of heme, the cytoskeletal resilience was lost, as filaments grew rampant in all directions, resulting in macrophage paralysis. The cells lost their ability to shape-shift and could no longer chase down and engulf the invading bacteria, allowing the bacteria to multiply virtually unrestricted.
However, Dr Knapp and her colleagues found that an antimalarial drug can restore the functionality of these paralyzed macrophages.
“Quinine, which is clinically used to treat malaria and is suspected to bind heme, blocks the interaction of heme with DOCK8 and thereby improves the outcome from sepsis,” Dr Knapp said.
“This is very promising. We conclusively demonstrate that it is indeed feasible to therapeutically ‘protect’ immune cells and to restore the body’s immune defense against bacteria in hemolytic conditions.”
plate showing a positive
streptococcus infection
Photo by Bill Branson
Patients who suffer from hemolysis have an increased risk of developing bacterial infections, and new research provides an explanation for this phenomenon.
The study refutes the idea that excess circulating iron is to blame.
Instead, it suggests that heme prevents macrophages from engulfing bacteria. And targeting this activity might reduce the risk of bacterial infection in patients with hemolytic disorders.
Sylvia Knapp, MD, PhD, of the Medical University of Vienna in Austria, and her colleagues reported these findings in Nature Immunology.
For decades, iron has been considered the prime suspect responsible for the high rate of bacterial infections in patients with hemolysis. Iron has long been established as an essential nutrient for bacteria.
Since hemolysis leads to the release of iron-containing heme, the threat of serious bacterial infections in these patients was attributed to the excess availability of circulating iron (heme).
However, Dr Knapp and her colleagues found that heme does not act as a willing nutrient to bacteria.
“Using in vitro and preclinical models, we could clearly demonstrate that heme-derived iron is not at all vital for bacterial growth,” said Rui Martins, a PhD student at the Medical University of Vienna.
“In contrast, we found that heme acts on macrophages, the most significant immune cells that are required for mounting an antibacterial response, and it furthermore prevented these cells from eliminating bacteria.”
Heme interfered with the cytoskeleton of macrophages, thereby immobilizing them.
“Heme causes cells to form numerous spikes—like hair standing on end—and then ‘stuns’ the cells within minutes,” Martins explained. “It is reminiscent of a cartoon character sticking his finger in an electrical outlet.”
The cytoskeleton is crucial for the basic functions of macrophages. It consists of long, branching filaments that act as the cell’s internal, highly flexible, and mobile framework.
Through targeted build-up and breakdown of these filaments, phagocytes can move in any direction and engulf invading bacteria. However, this requires a finely tuned signaling program in which the protein DOCK8 plays a central role.
“Through chemical proteomics and biochemical experiments, we discovered that heme interacted with DOCK8, which led to the permanent activation of its downstream target, Cdc42, with deleterious effects,” Dr Knapp said.
In the presence of heme, the cytoskeletal resilience was lost, as filaments grew rampant in all directions, resulting in macrophage paralysis. The cells lost their ability to shape-shift and could no longer chase down and engulf the invading bacteria, allowing the bacteria to multiply virtually unrestricted.
However, Dr Knapp and her colleagues found that an antimalarial drug can restore the functionality of these paralyzed macrophages.
“Quinine, which is clinically used to treat malaria and is suspected to bind heme, blocks the interaction of heme with DOCK8 and thereby improves the outcome from sepsis,” Dr Knapp said.
“This is very promising. We conclusively demonstrate that it is indeed feasible to therapeutically ‘protect’ immune cells and to restore the body’s immune defense against bacteria in hemolytic conditions.”